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Ciliated and non-ciliated mechanosensory cells in invertebrates have intricate cytoskeletal structures that, combined with microtubules, act as a mechanical link between external stimulus and signal processing. As a result, they can perceive forces like touch, cuticle deformation, gravity and sound. Through the expression of antibodies against serotonin (5-HT), calbindin, inducible nitric oxide synthase (iNOS) and a-smooth muscle actin (aSMA), this research aims to investigate mechanosensory cells in the integument of Lumbricus terrestris (Linnaeus, 1758) in an evolutionary perspective. In the epidermis, we discovered isolated mechanosensory cells that were immunopositive to every antibody examined. Our findings improve the knowledge and the evolution of annelid sensory biology adding new insights on the sensory signal transduction and help to better understand the morpho-structural adaptations of invertebrate skin on an evolutionary scale and to give more taxonomic data for species distinction. [ABSTRACT FROM AUTHOR]

Aim(s): To assess the effectiveness of sub‐epidermal moisture (SEM) assessment technology in the detection of early‐stage pressure damage in a critical care unit (CCU) and dark skin tone patients and its impact on hospital‐acquired pressure injury (HAPI) incidence. Design: Quality improvement study employing Kurt Lewin's change model emphasizing planning, implementation, evaluation and sustainable change. Methods: The study evaluated 140 adult patients admitted to the CCU over a 24‐week period, from July to December 2022. Retrospective analysis of standard PI care pathways was performed in 90 patients admitted during a 12‐week pre‐implementation period. Fifty patients were admitted through the subsequent 12‐week implementation period. SEM assessments were performed daily at the sacrum and heels and interventions were applied based on SEM assessments; SEM delta ≥0.6 indicating localized oedema or persistent focal oedema. Statistical analyses were performed on anonymized data. Results: Pre‐implementation HAPI incidence was 8.9% (N = 8/90). All eight patients were African American with varying skin tones. A 100% reduction in HAPI incidence was achieved in the implementation period which included 35 African American patients. The relative risk of HAPI incidence was 1.6 times higher in the pre‐implementation group. Conclusion: Implementing SEM assessment technology enabled equitable PI care for all population types and resulted in a 100% reduction of PIs in our CCU. Objective SEM assessments detected early‐stage PIs, regardless of skin tone and enabled providing interventions to specific anatomies developing tissue damage as opposed to universal preventive interventions. Implications: PI care pathways relying on visual and tactile skin assessments are inherently biased in providing equitable care for dark skin tone patients. Implementing SEM assessments empowers healthcare practitioners in driving objective clinical interventions, eliminates bias and enables positive PI health outcomes. Impact: Implementing SEM assessment technology had three main effects: it detected early tissue damage regardless of skin tone (detection effect), enabled anatomy‐specific interventions (treatment effect) and prevented PIs across all population types (prevention effect). The authors have adhered to the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines. Patient or Public Contribution: No patient or public contribution. What does this paper contribute to the wider global clinical community? Addressing health inequities in pressure injury prevention; Demonstrated effectiveness across patient populations; Resource optimization and enhanced patient safety. [ABSTRACT FROM AUTHOR]

Summary: Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities.We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues.Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships.The work suggests that mevalonate derived 30‐carbon alkaloids are formed in the phloem region before their conversion to 22‐carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress.We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in ex vivo skin explant tissue. The effect of GFF on cell adhesion rates, cellular ATP levels and proliferation rates were quantitated. Oxidative phosphorylation and glycolytic rates were measured under normal and stress‐induced conditions.Transcriptomics from keratinocytes and ex vivo skin explants from multiple donors show GFF induces keratinocyte differentiation, skin barrier development and cell adhesion while simultaneously repressing cellular stress and inflammatory related processes. Spatial transcriptomics profiling of ex vivo skin indicated basal keratinocytes at the epidermal‐dermal junction and cornifying keratinocytes in the top layer of the epidermis as the primary cell types influenced by GFF treatment. Additionally, GFF significantly increases crosstalk between suprabasal and basal keratinocytes. To support these findings, we show that GFF can significantly increase cell adhesion and proliferation in keratinocytes. GFF also protected overall cellular bioenergetics under metabolic or oxidative stress conditions.Our findings provide novel insights into cellular differences and epidermal spatial localization in response to GFF, supporting previous findings that this filtrate has a significant impact on epidermal biology and homeostasis, particularly on spatially defined crosstalk. We propose that GFF can help maintain epidermal health by enhancing keratinocyte crosstalk and differentiation/proliferation balance as well as promoting an enhanced response to stress. [ABSTRACT FROM AUTHOR]

Earthworms are fascinating animals capable of crawling and burrowing through various terrains using peristaltic motion and the directional friction response of their epidermis. Anisotropic anchoring governed by tiny appendages on their skin called setae is known to enhance the earthworm's locomotion. A multi‐material fabrication technique is employed to produce soft skins with bristles inspired by the earthworm epidermis and their setae. The effect of bristles arranged in triangular and square grids at two spatial densities on the locomotion capability of a simple soft crawling robot comprised of an extending soft actuator covered by the soft skin is investigated experimentally. The results suggest that the presence of bristles results in a rostral to caudal friction ratio of µR/µC > 1 with some variations across bristle arrangements and applied elongations. Doubling the number of bristles increases the robot's speed by a factor of 1.78 for the triangular grid while it is less pronounced for the rectangular grid with a small factor of 1.06. Additionally, it is observed that increasing the actuation stroke for the skin with the high‐density triangular grid, from 15% to 30%, elevates the speed from 0.5 to 0.9 mm s−1, but further increases in stroke to 45% may compromise the durability of the actuators with less gains in speed (1 mm s−1). Finally, it is demonstrated that a crawling robot equipped with soft skin can traverse both a linear and a curved channel. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Summary: Leaf venation is a pivotal trait in the success of vascular plants. Whereas gymnosperms have single or sparsely branched parallel veins, angiosperms developed a hierarchical structure of veins that form a complex reticulum. Its physiological consequences are considered to have enabled angiosperms to dominate terrestrial ecosystems in the Late Cretaceous and Cenozoic.Although a hierarchical‐reticulate venation also occurs in some groups of extinct seed plants, it is unclear whether these are stem relatives of angiosperms or have evolved these traits in parallel. Here, we re‐examine the morphology of the enigmatic foliage taxon Furcula, a potential early Mesozoic angiosperm relative, and argue that its hierarchical vein network represents convergent evolution (in the Late Triassic) with flowering plants (which developed in the Early Cretaceous) based on details of vein architecture and the absence of angiosperm‐like stomata and guard cells.We suggest that its nearest relatives are Peltaspermales similar to Scytophyllum and Vittaephyllum, the latter being a genus that originated during the Late Triassic (Carnian) and shares a hierarchical vein system with Furcula.We further suggest that the evolution of hierarchical venation systems in the early Permian, the Late Triassic, and the Early Cretaceous represent 'natural experiments' that might help resolve the selective pressures enabling this trait to evolve. [ABSTRACT FROM AUTHOR]

The polygonal shape of cells in proliferating epithelia is a result of the tensile forces of the cytoskeletal cortex and packing geometry set by the cell cycle. In the larval Drosophila epidermis, two cell populations, histoblasts and larval epithelial cells, compete for space as they grow on a limited body surface. They do so in the absence of cell divisions. We report a striking morphological transition of histoblasts during larval development, where they change from a tensed network configuration with straight cell outlines at the level of adherens junctions to a highly folded morphology. The apical surface of histoblasts shrinks while their growing adherens junctions fold, forming deep lobules. Volume increase of growing histoblasts is accommodated basally, compensating for the shrinking apical area. The folded geometry of apical junctions resembles elastic buckling, and we show that the imbalance between the shrinkage of the apical domain of histoblasts and the continuous growth of junctions triggers buckling. Our model is supported by laser dissections and optical tweezer experiments together with computer simulations. Our analysis pinpoints the ability of histoblasts to store mechanical energy to a much greater extent than most other epithelial cell types investigated so far, while retaining the ability to dissipate stress on the hours time scale. Finally, we propose a possible mechanism for size regulation of histoblast apical size through the lateral pressure of the epidermis, driven by the growth of cells on a limited surface. Buckling effectively compacts histoblasts at their apical plane and may serve to avoid physical harm to these adult epidermis precursors during larval life. Our work indicates that in growing nondividing cells, compressive forces, instead of tension, may drive cell morphology. During the development of the larval Drosophila epidermis, histoblasts and epithelial cells compete for space as they grow and undergo morphological changes. This study shows that compressive forces play a key role in controlling the shape of histoblasts, leading to the buckling of their apical junctions and changing the morphology of the epidermis from straight to highly folded outlines. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is a common skin cancer, often caused by exposure to ultraviolet radiation (UVR). Recent studies have shown that changes in DNA methylation play a crucial role in the development of cancers. However, methylation patterns of SCC are not well characterised. Identifying biomarkers for the risk of developing SCC could be helpful for early detection and diagnosis and can potentially improve treatment and prevention strategies. This study aimed to investigate methylation changes in the epidermis of mice exposed to UVR for 24 weeks. We examined the DNA methylation levels of 260 199 CpGs using the Illumina Infinium Mouse Methylation BeadChip and studied the epidermis of UVR‐exposed and unexposed mice every 4 weeks for 24 weeks (n = 39). We identified CpGs with large differences in methylation levels (β‐values) between UVR‐exposed and unexposed mice. We also observed differences in the epigenetic age of these mice. We identified CpGs in Rev, Ipmk, Rad51b, Fgfr2, Fgfr3 and Ctnnb1 that may serve as potential biomarkers for SCC risk and could be helpful for the early detection and prevention of SCC. Further investigations are necessary to determine the biological functions and clinical significance of these CpGs. [ABSTRACT FROM AUTHOR]

This electron microscope study investigated the micromorphological characteristics of the leaf epidermis of 5 species (10 populations) of Ribes (Grossulariaceae) in Iran: R. biebersteinii, R. uva‐crispa, R. orientale, R. aureum, and R. khorasanicum. Samples were collected and identified, and the similarities between the species were evaluated using information from micromorphological traits of leaf epidermis and multivariate analysis (cluster analysis and principal component analysis). The traits useful for discriminating the species were presence or absence of hairs and glandular trichomes, presence or absence of granular with verrucae on hair surface, position of hairs on epidermal surface, hair location on the leaf (lamina, leaf margin, midrib), stomata shape, wax distribution on stomata, prominence and shape of anticlinal walls and outer periclinal layer, and epicuticular wax sculpturing. An identification key based on these leaf micromorphological characters is provided for Ribes species in Iran. The multivariate analysis of micromorphological traits was efficient for inter‐ and intra‐specific delimitation. The present findings correspond to a large extent with existing classifications. [ABSTRACT FROM AUTHOR]

The genus Bolboschoenus has been intensively studied from the morphological, ecological and physiological aspects, however, anatomical features of stems, leaves and epidermal structures of leaves have not been investigated sufficiently yet. The main objective of this study was to compare the four Bolboschoenus species growing in Serbia at the anatomical level and to define the most important anatomical characteristics for distinguishing these species. Descriptive, nonmetric multidimensional scaling and canonical discriminant analysis of the anatomical characters of leaves, stems and epidermal structures have been conducted for these purposes. The number and position of sclerenchyma strands in the leaves, the presence of bulliform cells in the epidermis, the number of translucent cell layers under the adaxial epidermis in the midrib area of the lamina, the number of aerial cavities in leaves and stems were the most significant anatomical characters for differentiation of species. The most differentiated species was B. glaucus, while B. laticarpus occupied an intermediate position between B. maritimus and B. planiculmis, on the one hand, and B. glaucus on the other. The combination of the anatomical features of leaves and stems and the epidermal structures had a more excellent taxonomic value than these three individual groups of features individually. [ABSTRACT FROM AUTHOR]

Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins. We found that stronger expression of KRT16 indeed corresponds to stronger expression of S100A7 in our clinical melanoma samples. We also report a trend regarding staining of GLI1, which corresponds to stronger staining of GLI3, KRT16, and S100A7 proteins. The most interesting of our findings is that all the proteins are detected specifically in the epidermis overlying the tumor, but rarely in the tumor itself. The examined proteins were also not detected in the healthy epidermis at the edges of the sample, suggesting that the staining is specific to the epidermis overlaying the tumor mass. Of all proteins, only S100A7 demonstrated a statistically significant trend regarding tumor staging and staining intensity. Results from our clinical samples prove that immune infiltration is an important feature of melanoma. Pigmentophages and tumor-infiltrating lymphocytes (TIL) demonstrate a significant association with tumor stage, while mononuclear cells are equally present in all stages. For S100A7, we found an association between the number of TILs and staining intensity. Considering these new findings presented in our study, we suggest a more detailed examination of the possible role of the S100A7 protein as a biomarker in melanoma. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (FLG) is an essential protein that plays a vital role in maintaining skin barrier function and moisture levels, allowing the skin to adapt to dry environments. However, the precise temporal dynamics of FLG metabolism in the human epidermis remain poorly understood, and suitable tools to study these time‐dependent effects are currently lacking. Objective: To investigate the molecular mechanisms and time course of FLG metabolism and skin barrier function under high‐ and low‐humidity conditions, utilizing a reconstructed epidermis model. Methods: EpiSkin specimens cultured under humid or dry conditions for varying durations (2–48 h) were compared by assessing FLG degradation and skin barrier formation using immunofluorescence staining and western blotting. Results: Under conditions of low humidity, the proteolysis of FLG in EpiSkin increased between 4 and 12 h and was accompanied by elevated levels of cysteine–aspartic protease (caspase)‐14. The expression of peptidyl arginine deiminase 1 and calpain 1 also increased at 4 h. However, after 24 h, the expression of these three FLG‐degrading proteins significantly decreased. Conversely, the levels of pyrrolidone‐5‐carboxylic acid and urocanic acid initially decreased at 2 h and then increased between 12 and 24 h. Additionally, the expression of skin barrier proteins, such as FLG, transglutaminase 5, loricrin and zonula occludens‐1, decreased starting from 12 h. Notably, epidermal cell viability and activity were also inhibited. Conclusion: We propose a reliable and ethical model to study the temporal dynamics of FLG metabolism and its role in skin barrier function. Using a commercially reconstructed epidermis to mimic dry skin formation obviates the need for animal and human testing. [ABSTRACT FROM AUTHOR]

Lotus rhizome is an important aquatic vegetable, but the blackening of lotus rhizome epidermis (LRE) seriously affects its appearance and quality, which makes lotus rhizome products unmarketable. In this study, the effects of polyphenols and iron on the LRE color were studied to explore the possible mechanism of LRE blackening. Results indicated that the measurable total phenols contents in the mud treatment (MT) group were significantly reduced, and the total iron contents were significantly increased compared with the bruised treatment group (p < 0.05). The high‐performance liquid chromatography results showed that the main polyphenols in LRE were dopa, gallocatechin, and catechin, as well as a small amount of catechol, epicatechin, proanthocyanidin B2, and proanthocyanidin C1. Moreover, the results of color difference and ultraviolet adsorption spectroscopy showed that there were obviously black or brown‐gray of dopa (525 nm), gallocatechin (504.5 nm), and catechin (550 and 504.5 nm) with FeCl2. The simulated system treatment of LRE further confirmed that the chromaticity effect of dopa and iron in bruised LRE was similar to that of the MT group, whereas 1% (w/w) ascorbic acid, 2% (w/w) EDTA‐2Na, or 3% (w/w) citric acid could solely prohibit the blackening. This suggested that the dopa in LRE and FeCl2 in mud may mainly combine into [2(DOPA‐2H+)+Fe3+]− through non‐covalent interaction, which leads to the blackening of bruised LRE under neutral conditions. These results can guide the storage of lotus rhizomes and improve the development of the lotus rhizome industry. [ABSTRACT FROM AUTHOR]

The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin‐related diseases in humans. Here, single‐cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross‐species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome‐wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin‐related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor‐like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in‐depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models. [ABSTRACT FROM AUTHOR]

One of the major functions of the semaphorin signaling system is the regulation of cell shape. In the nematode Caenorhabditis elegans, membrane‐bound semaphorins SMP‐1/2 (SMPs) regulate the morphology of epidermal cells via their receptor plexin, PLX‐1. In the larval male tail of the SMP‐PLX‐1 signaling mutants, the border between two epidermal cells, R1.p and R2.p, is displaced anteriorly, resulting in the anterior displacement of the anterior‐most ray, ray 1, in the adult male. To elucidate how the intercellular signaling mediated by SMPs regulates the position of the intercellular border, we performed mosaic gene expression analyses by using infrared laser‐evoked gene operator (IR‐LEGO). We show that PLX‐1 expressed in R1.p and SMP‐1 expressed in R2.p are required for the proper positioning of ray 1. The result suggests that SMP signaling promotes extension, rather than retraction, of R1.p. This is in contrast to a previous finding that SMPs mediate inhibition of cell extension of vulval precursor cells, another group of epidermal cells of C. elegans, indicating the context dependence of cell shape control via the semaphorin signaling system. [ABSTRACT FROM AUTHOR]

Transdermal transport can be challenging due to the difficulty in diffusing active substances through the outermost layer of the epidermis, as the primary function of the skin is to protect against the entry of exogenous compounds into the body. In addition, penetration of the epidermis for substances hydrophilic in nature and particles larger than 500 Da is highly limited due to the physiological properties and non-polar nature of its outermost layer, namely the stratum corneum. A solution to this problem can be the use of microneedles, which "bypass" the problematic epidermal layer by dispensing the active substance directly into the deeper layers of the skin. Microneedles can be obtained with various materials and come in different types. Of special interest are carriers based on biodegradable and biocompatible polymers, such as polysaccharides. Therefore, this paper reviews the latest literature on methods to obtain hyaluronic acid-based microneedles. It focuses on the current advancements in this field and consequently provides an opportunity to guide future research in this area. [ABSTRACT FROM AUTHOR]

Although laurocapram (Azone) significantly enhances the skin permeation of drugs, its development was hindered by its skin irritation. We then developed an Azone-mimic ionic liquid (IL-Azone), composed of less irritating cationic ε -caprolactam and anionic myristic acid. IL-Azone dissociates to the original cation and anion in the presence of water in the formulation. We tried to select a formulation suitable for IL-Azone in the present study. Each formulation contained 5 % of either Azone or IL-Azone along with the model drug antipyrine, and skin permeation experiments of the drug were conducted. The results revealed that IL-Azone did not enhance skin permeation when combined with most formulations tested. However, a notable and rapid enhancement in skin permeation was observed when combined with white petrolatum. This effect could be attributed to the minimal water content in white petrolatum, which prevented IL-Azone degradation. Furthermore, its permeation-enhancing effects from IL-Azone in white petrolatum were more pronounced and rapid than Azone. The rapid onset observed with IL-Azone can be attributed to its degradation into its original components at the interface between the stratum corneum and the living epidermis, which results in a shorter lag time before achieving a steady-state concentration in the SC compared to Azone. [ABSTRACT FROM AUTHOR]

Chinese plum (Prunus salicina Lindl.) originates from China and makes a large contribution to the global production of plums. The P. salicina 'Wushancuili' has a green coloration and high fruit quality and is economically important in eliminating poverty and protecting ecology in the Yangtze River Three Gorges Reservoir. However, rain-induced cracking (rain-cracking, literally skin cracking caused by rain) is a limitation to 'Wushancuili' fruit production and causes severe losses. This study reported a high-quality 'Wushancuili' genome assembly consisting of a 302.17-Mb sequence with eight pseudo-chromosomes and a contig N50 of 23.59 Mb through the combination of Illumina sequencing, Pacific Biosciences HiFi III sequencing, and high-throughput chromosome conformation capture technology. A total of 25 109 protein-coding genes are predicted and 54.17% of the genome is composed of repetitive sequences. 'Wushancuili' underwent a remarkable orthoselection during evolution. Gene identification revealed that loss-of-function in four core MYB10 genes results in the anthocyanin deficiency and absence of red color, revealing the green coloration due to the residual high chlorophyll in fruit skin. Besides, the occurrence of cracking is assumed to be closely associated with cell wall modification and frequently rain-induced pathogen enrichment through transcriptomic analysis. The loss of MYB10 genes might render fruit more susceptible to pathogen-mediated cracking by weakening the epidermal strength and reactive oxygen species (ROS) scavenging. Our findings provided fundamental knowledge regarding fruit coloration and rain-cracking and will facilitate genetic improvement and cultivation management in Chinese plums. [ABSTRACT FROM AUTHOR]

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result. Key Words: burn wound infections; biofilm; epidermis; hospital; opportunistic infection [ABSTRACT FROM AUTHOR]

Mangifera indica var Ataulfo is the main variety grown in the Soconusco region of Chiapas, Mexico and faces a decrease in firmness and weight loss due to hydrothermal treatment, in addition to non-uniform ripening and consequently a decrease in price as the harvest period lengthens. In order to improve the postharvest quality of the "Ataulfo" mango fruit, preharvest applications of aminoethoxyvinylglycine (AVG; ReTain®, a.i. 15%) were carried out in "La Norteña" with Phaeozem soil, 1500 mm of annual precipitation, and applications of agrochemicals, and in "Santa Cecilia" with Acrisol soil, 2500 mm of annual precipitation, and without agrochemicals. The treatments were: (1) Control, (2) One application 7 days before harvest (0.1 g L−1), (3) Two applications (14 days and 7 days before harvest, 0.2 g L−1) and (4) Three applications (21, 14 and 7 days before harvest, in total 0.3 g L−1), with completely randomized design in the laboratory. The results show contrasting differences between the evaluation sites, with lower weight loss (18.4%) and 3.1% more firmness in a drier climate and higher soil calcium content. The average firmness (N) on day 14 was 18.3 and with three applications of AVG it was 22.0. The °Brix at the end of the study in the control was 11.3 and on average with AVG applications it was 14.4. Three-time applications of AVG in preharvest delayed the weight loss with an increase in the maintenance of the firmness of the fruits. The weight of the fruit epidermis was lower with AVG applications, and increased with the number of applications. [ABSTRACT FROM AUTHOR]

Cornulin (CRNN) and repetin (RPTN) belong to the fused‐type S100 protein family. Although these proteins have been reported to be expressed in the granular layer of the epidermis and have been suggested to be associated with barrier formation in the epidermis, their exact function remains unclear. This study examined the effects of ultraviolet B (UVB) irradiation on CRNN and RPTN expression in human skin xenotransplantation. The CRNN expression increased in the granular layer of UVB‐irradiated skin 2 days after UVB irradiation compared to that in sham‐irradiated skin. Interestingly, CRNN signals were observed not only in the cytoplasm, but also in the peripheral regions of granular keratinocytes. In contrast, RPTN was rarely expressed in sham‐irradiated skin; however, RPTN signals were markedly increased in the granular layer of the UVB‐irradiated skin. In addition, activation of ERK1/2 and STAT3 was observed in UVB‐irradiated skin. Accordingly, the present study demonstrated that CRNN and RPTN are novel proteins whose expression can be increased by UVB irradiation. The activation of ERK1/2 and STAT3 may be associated with the regeneration of a UVB‐damaged epidermis, and CRNN and RPTN may be induced to repair any dysfunction in the epidermal barrier during this regeneration process. [ABSTRACT FROM AUTHOR]

Differences in stomatal density (SD) and stomatal index (SI) are associated with the conditions of the environment in which they are distributed. Mimosa species are important elements in different plant communities, yet knowledge of the ecological implications of its stomatal characteristics is scarce. For this reason, SD and SI were determined in seven Mimosa species from different environments in this study. Five individuals per species were selected, and a sample of leaflets was obtained from each. Fifteen mature leaflets per individual were then extracted and observed by optical microscopy. SD, SI, epidermal cell density (ECD), and guard cell length (GCL) values were obtained. Differences between species were analyzed through a balanced analysis of variance test, and the correspondence between the stomatal characteristics and 21 climate variables was determined by canonical correspondence analysis. The species differed in all evaluated characteristics. It should be noted that only M. affinis showed differences between the leaflet surfaces. Both DE and ECD were negatively associated with altitude and solar radiation and positively with temperature and precipitation. SI was explained by temperature and seasonality of precipitation, and GCL by temperature oscillation and seasonality of precipitation. The results suggest that the stomatal characteristics of the leaflets confer resistance in the species to alterations in environmental conditions. [ABSTRACT FROM AUTHOR]

The mammalian epidermis has evolved to protect the body in a dry environment. Genes of the epidermal differentiation complex (EDC), such as FLG (filaggrin), are implicated in the barrier function of the epidermis. Here, we investigated the molecular evolution of the EDC in sirenians (manatees and dugong), which have adapted to fully aquatic life, in comparison to the EDC of terrestrial mammals and aquatic mammals of the clade Cetacea (whales and dolphins). We show that the main subtypes of EDC genes are conserved or even duplicated, like late cornified envelope (LCE) genes of the dugong, whereas specific EDC genes have undergone inactivating mutations in sirenians. FLG contains premature stop codons in the dugong, and the ortholog of human CASP14 (caspase-14), which proteolytically processes filaggrin, is pseudogenized in the same species. As FLG and CASP14 have also been lost in whales, these mutations represent convergent evolution of skin barrier genes in different lineages of aquatic mammals. In contrast to the dugong, the manatee has retained functional FLG and CASP14 genes. FLG2 (filaggrin 2) is truncated in both species of sirenians investigated. We conclude that the land-to-water transition of sirenians was associated with modifications of the epidermal barrier at the molecular level. [ABSTRACT FROM AUTHOR]

The integrity of the stratum corneum is essential for skin hydration. In order to fulfill all of its functions, a balance of the water content in the stratum corneum is necessary, as well as maintaining the epidermis, an essential objective of cosmetic formulations. Cosmetic skin hydration can be achieved through the frequent application of cosmetic products that can act through basic mechanisms: occlusion, moisturization, and hydration or active moisturization. Therefore, when developing new cosmetic products, it is important to consider their positive effect on skin hydration and viscoelasticity, considering that the objective of a cosmetic product is to protect the skin and delay skin aging. Subsequently, multiple O/W/O emulsions were developed and skin hydration was evaluated in vitro and in vivo. The in vitro method for skin hydration employs gelatin whose composition mimics collagen and NMF of the skin, forming a surface (1 cm thick) through which internal water vapor can be released. The occlusion provided to this gelatin surface is evaluated, and the hydrating power of the applied products is determined. Due to the composition of the gelatin support cell and the evaporation of water inside it, it can simulate TEWL of the skin. The in vivo evaluation of hydration, pH, and sebum of the aqueous solution of proteins, simple O/W, and multiple O/W/O with collagen showed that O/W/O emulsions provided greater occlusive and oily content, maintaining the pH levels of the skin. Therefore, these O/W/O systems improve conditions for dry skin. Scheme of the gelatin support cells before (A) and after (B) the application of the O/WCo/O multiple emulsions. [ABSTRACT FROM AUTHOR]

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin. [ABSTRACT FROM AUTHOR]

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all‐around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold‐bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications. [ABSTRACT FROM AUTHOR]

Background: The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet (UV) irradiation. UV irradiation, mainly UVB at wavelength of 280–315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. Summary: While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. Key Message: Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents. The radiation destroys the repair mechanism, resulting in delayed or prolonged wound healing. It still lacks an effective therapeutic strategy currently. OBJECTIVE: To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury, which are designed to be antibacteria, promoted healing and analgesics. METHODS: Using levofloxacin, fibroin and lidocaine hydrochloride as raw materials, 3D bioprinting technology was applied to prepare the multifunctional wound dressing. (1) The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and incubated at 37 °C overnight to detect the diameter of the antibacterial zone. (2) 40 Kunming mice were randomly divided into trauma group, radiation and trauma model group, treatment group and positive drug group, with 10 mice in each group. Mice in the radiation and trauma model group, treatment group and positive drug group were irradiated by 60Co gamma rays. After 1 hour of radiation, a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups. Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group. Trethanolamine cream was applied to the wounds of the positive drug group. Multifunctional dressing was applied to the wounds of the treatment group. The dressing was changed every 2 days, and the treatment was continued for 14 days. Wound healing rate and serum interleukin-6 level were measured at 3, 7 and 14 days after wound modeling. 14 days after the wound modeling, the skin tissue of the wound was obtained and received hematoxylin-eosin staining, Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION: (1) 3D-printed multifunctional wound dressing had good antibacterial activity. The antibacterial zone diameters against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were (4.15±0.09), (4.18±0.23) and (4.35±0.13) cm, respectively. (2) With the extension of modeling time, the wound healed gradually. The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3, 7 and 14 days after modeling (P < 0.01, P < 0.001). The wound healing rate of the treatment group was higher than that of the positive drug group. With the extension of modeling time, the serum interleukin level of mice increased first and then decreased. The serum interleukin level in the treatment group at 3, 7 and 14 days after modeling was lower than that in the radiation and trauma model group. Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group, and the dermal collagen fibers were densely arranged. The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group. In the treatment group, normal skin mucosal tissue was observed, the epidermis was arranged closely, and the sweat glands, hair follicles and dermal collagen fibers were arranged regularly. In the positive drug group, the arrangement of epidermal layer was tight, and the arrangement of sweat glands, hair follicles and dermal collagen fibers was regular. Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups (P < 0.01, P < 0.001). (3) The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia, anti-infection and promoting healing. [ABSTRACT FROM AUTHOR]

In this paper, a temperature-controlled angle selection device based on a photonic bandgap is proposed, consisting of MLC-6608 liquid crystal (MLC) and common electrolytes stacked in layers. This device has an angular transmission stability for electromagnetic waves over a wide frequency band (600–660 THz). A high transmissivity (T > 0.85) area, also called an angle window, is formed at 25 ° and 75 ° , and an area of zero transmissivity is formed beyond the angle window. The MLC is temperature-responsive, and the range of angle selection can be expanded or narrowed by temperature adjustment. When the MLC is replaced by the biological sample, it shows good sensing performance. It can be used to detect in vitro dermis, in vivo stratum corneum, and in vivo epidermis and it is of great significance in medicine, with a sensing sensitivity of 90.91 ° /refractive index unit. [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]

Aquaporin 3 (AQP3) channels are tetrameric membrane-bound channels that facilitate the transport of water and other small solutes across cell membranes in the skin. Decreased AQP3 expression is associated with skin dryness, skin aging, psoriasis, and delayed wound healing. Thus, our study focused on a novel combination based on Aloe barbadensis leaf extract and trimethylglycine for targeted AQP3 regulation in skin keratinocytes and deep skin moisturization. Firstly, a dose-finding cytotoxicity assay of the selected substances was performed with a 2,5-diphenyl-2H-tetrazolium bromide (MTT) indicator on HaCaT cells. The substances' ability to increase the amount of AQP3 in keratinocytes was evaluated in a keratinocyte cell culture by means of ELISA. Additionally, the deep skin hydration effect was confirmed in clinical research with healthy volunteers. According to the results, the maximum tolerated doses providing viability at 70% (MTDs) values for Aloe barbadensis leaf extract and trimethylglycine were 24.50% and 39.00%, respectively. Following the research and development, a complex based on Aloe barbadensis leaf extract and trimethylglycine in a 1:1 mass ratio exhibited a good cytotoxicity profile, with an MTDs value of 37.90%. Furthermore, it was shown that the combination had a clear synergetic effect and significantly increased AQP3 by up to 380% compared to the negative control and glyceryl glucoside (p < 0.001). It was clinically confirmed that the developed shower gel containing Aloe barbadensis leaf extract and trimethylglycine safely improved skin hydration after one use and over 28 days. Thus, this novel plant-based combination has promising potential for AQP3 regulation in the skin epidermis and a role in the development of dermatological drugs for the treatment of skin xerosis and atopic-related conditions. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar lichen sclerosus (VLS) is a chronic progressive, lymphocyte-mediated inflammatory disease whose pathogenesis is complex and not fully elucidated. Aim: In the current study we have investigated for the first time the expression of interleukin-17 (IL-17) and S100A7 in lesional skin obtained from female individuals with histologically confirmed VLS. Material and methods: In our study we used skin biopsies obtained from female patients with histologically confirmed VLS (n = 20) and skin samples from healthy age- and gender-matched individuals (plastic surgery procedures) (n = 10) serving as controls. The tissue expressions of IL-17 and S100A7 were assessed with an immunohistochemical method. Results: The number of cells showing IL-17 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, IL-17 was expressed in the epidermis and by cells within the inflammatory infiltrate in the upper dermis. The number of cells showing S100A7 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, S100A7 was expressed by suprabasal keratinocytes in epidermis. S100A7 was also expressed by cells within the inflammatory infiltrate in the dermis. Conclusions: The results of our study may suggest the involvement of IL-17 and S100A7 in the pathogenesis of VLS. The better understanding of this disease may lead to the development of novel, effective therapeutic strategies e.g. using well-known biologics IL-17 inhibitors class. [ABSTRACT FROM AUTHOR]

Summary Skin care is currently experiencing two developments. On the one hand, there is a move away from skin‐affecting additives and an increasing use of physiological ingredients, i.e., substances that are natural to the body or are metabolised by the body without side effects. On the other hand, special attention is being paid to the harmonisation of the individual substances and the overall compositions with the skin microbiome. Phosphatidylserine – a component from the group of phospholipids that has been known for a long time – is establishing itself in skin care and does justice to both developments. [ABSTRACT FROM AUTHOR]

The epidermis is a stratified epithelium that forms the outer layer of the skin. It is composed primarily of keratinocytes and is constantly renewed by the proliferation of stem cells and their progeny that undergo terminal differentiation as they leave the basal layer and migrate to the skin surface. Basal keratinocytes rest on a basement membrane composed of an extracellular matrix that controls their fate via integrin‐mediated focal adhesions and hemidesmosomes which are critical elements of the epidermal barrier and promote its regenerative capabilities. The distribution of basal cells with optimal activity provides the basement membrane with its characteristic undulating shape; this configuration disappears with age, leading to epidermal weakness. In this study, we present an in‐depth imaging analysis of basal keratinocyte anchorage in samples of human skin from participants across the age spectrum. Our findings reveal that skin aging is associated with the depletion of hemidesmosomes that provide crucial support for stem cell maintenance; their depletion correlates with the loss of the characteristic basement membrane structure. Atomic force microscopy studies of skin and in vitro experiments revealed that the increase in tissue stiffness observed with aging triggers mechanical signals that alter the basement membrane structure and reduce the extent of basal keratinocyte anchorage, forcing them to differentiate. Genomic analysis revealed that epidermal aging was associated with mechanical induction of the transcription factor Krüppel‐like factor 4. The altered mechanical properties of tissue being a new hallmark of aging, our work opens new avenues for the development of skin rejuvenation strategies. [ABSTRACT FROM AUTHOR]

Rexinoids are agonists of nuclear rexinoid X receptors (RXR) that heterodimerize with other nuclear receptors to regulate gene transcription. A number of selective RXR agonists have been developed for clinical use but their application has been hampered by the unwanted side effects associated with the use of rexinoids and a limited understanding of their mechanisms of action across different cell types. Our previous studies showed that treatment of organotypic human epidermis with the low toxicity UAB30 and UAB110 rexinoids resulted in increased steady-state levels of all-trans-retinoic acid (ATRA), the obligatory ligand of the RXR-RAR heterodimers. Here, we investigated the molecular mechanism underlying the increase in ATRA levels using a dominant negative RXRα that lacks the activation function 2 (AF-2) domain. The results demonstrated that overexpression of dnRXRα in human organotypic epidermis markedly reduced signaling by resident ATRA, suggesting the existence of endogenous RXR ligand, diminished the biological effects of UAB30 and UAB110 on epidermis morphology and gene expression, and nearly abolished the rexinoid-induced increase in ATRA levels. Global transcriptome analysis of dnRXRα-rafts in comparison to empty vector-transduced rafts showed that over 95% of the differentially expressed genes in rexinoid-treated rafts constitute direct or indirect ATRA-regulated genes. Thus, the biological effects of UAB30 and UAB110 are mediated through the AF-2 domain of RXRα with minimal side effects in human epidermis. As ATRA levels are known to be reduced in certain epithelial pathologies, treatment with UAB30 and UAB110 may represent a promising therapy for normalizing the endogenous ATRA concentration and signaling in epithelial tissues. [ABSTRACT FROM AUTHOR]

Bioinks play a fundamental role in skin bioprinting, dictating the printing fidelity, cell response, and function of bioprinted 3D constructs. However, the range of bioinks that support skin cells' function and aid in the bioprinting of 3D skin equivalents with tailorable properties and customized shapes is still limited. In this study, we describe a bioinspired design strategy for bioengineering double crosslinked pectin-based bioinks that recapitulate the mechanical properties and the presentation of cell-adhesive ligands and protease-sensitive domains of the dermal extracellular matrix, supporting the bioprinting of bilayer 3D skin models. Methacrylate-modified pectin was used as a base biomaterial enabling hydrogel formation via either chain-growth or step-growth photopolymerization and providing independent control over bioink rheology, as well as the mechanical and biochemical cues of cell environment. By tuning the concentrations of crosslinker and polymer in bioink formulation, dermal constructs were bioprinted with a physiologically relevant range of stiffnesses that resulted in strikingly site-specific differences in the morphology and spreading of dermal fibroblasts. We also demonstrated that the developed thiol-ene photo-clickable bioinks allow for the bioprinting of skin models of varying shapes that support dermis and epidermis reconstruction. Overall, the engineered bioinks expand the range of printable biomaterials for the extrusion bioprinting of 3D cell-laden hydrogels and provide a versatile platform to study the impact of material cues on cell fate, offering potential for in vitro skin modeling. [ABSTRACT FROM AUTHOR]

Background: Stressed, damaged or very aged skin is predominantly characterized by a malfunctioning skin barrier. Underlying skin barrier malfunction is a reduced or defective calcium gradient in the epidermis. Consequently, replenishing the compromised skin's calcium stores with topical calcium could be a potential therapeutic approach. Methods: We investigated the effect of our novel Ca2+ double cone vector system on improving the differentiation and barrier function of reconstructed human epidermis (RHE), cultured at low basal calcium (0.3 mM) to represent very aged skin. Furthermore, in a randomized placebo‐controlled clinical study the skin barrier of 20 healthy volunteers was challenged with 2% sodium lauryl sulphate (SLS) for 24 h under occlusion, following and/or prior to treatment with a gel containing 2% of our calcium vector system. Results: Culture in reduced basal calcium conditions (0.3 mM) strongly impeded the formation of a dense stratified epidermis. The apical treatment with 1.1 mM CaCl2 was not able to restore a functional differentiation. Treatment with 0.1% of the Ca2+ delivery system rescued the differentiation process and resulted in a normal stratified epidermis. Clinically, application of the Ca2+ vector system prior to and following SLS stress prevented increases in skin irritation and transepidermal water loss (TEWL) compared to placebo controls. Importantly, the treatment also significantly accelerated the recovery time following SLS stress. Conclusion: With our novel Ca2+ vector system, we highlight the delivery of bioavailable Ca2+ ions into the skin as a new and successful approach to treat a damaged barrier present in stressed, aged or atopic skin. [ABSTRACT FROM AUTHOR]

A claw bed inverted squamous papilloma (ISP) presented clinically as a swollen digit in a dog. Canine papillomavirus (CPV) type 2 was amplified by PCR and localised to the papilloma's epidermis using in situ hybridisation. This is the first report demonstrating a claw bed ISP caused by CPV. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the human body and serves various functions, including mechanical protection and mechanosensation. Yet, even though skin's biomechanics are attributed to two main layers—epidermis and dermis—computational models have often treated this tissue as a thin homogeneous material or, when considering multiple layers, have ignored the most prominent heterogeneities of skin seen at the mesoscale. Here, we create finite element models of representative volume elements (RVEs) of skin, including the three-dimensional variation of the interface between the epidermis and dermis as well as considering the presence of hair follicles. The sinusoidal interface, which approximates the anatomical features known as Rete ridges, does not affect the homogenized mechanical response of the RVE but contributes to stress concentration, particularly at the valleys of the Rete ridges. The stress profile is three-dimensional due to the skin's anisotropy, leading to high-stress bands connecting the valleys of the Rete ridges through one type of saddle point. The peaks of the Rete ridges and the other class of saddle points of the sinusoidal surface form a second set of low-stress bands under equi-biaxial loading. Another prominent feature of the heterogeneous stress pattern is a switch in the stress jump across the interface, which becomes lower with respect to the flat interface at increasing deformations. These features are seen in both tension and shear loading. The RVE with the hair follicle showed strains concentrating at the epidermis adjacent to the hair follicle, the epithelial tissue surrounding the hair right below the epidermis, and the bulb or base region of the hair follicle. The regions of strain concentration near the hair follicle in equi-biaxial and shear loading align with the presence of distinct mechanoreceptors in the skin, except for the bulb or base region. This study highlights the importance of skin heterogeneities, particularly its potential mechanophysiological role in the sense of touch and the prevention of skin delamination. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an unusual skin tumor that has a significant rate of distant and local metastases. It is known that primary MCC of the eyelid usually occurs at the upper eyelid. Here we report an unusual case of MCC metastasis to the eyelid. A 63-year-old male was diagnosed with MCC three years earlier after initially presenting with a mass in his right thigh. After histopathological diagnosis, the patient received medical therapy. During treatment, he developed multiple distant metastases and a firm, purple, vascularized lesion on the upper eyelid. We confirmed the lesion was an eyelid metastasis of MCC by histopathological examination and imaging methods. This case shows that extraocular MCC can metastasize to the eyelids, particularly the upper eyelid, where primary periocular MCC usually appears. [ABSTRACT FROM AUTHOR]

Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes. In a 3D organotypic human epidermis model, loss of DPM1 caused impaired differentiation with abnormally increased cornification, reduced thickness of non-corneal layers, and formation of intercellular gaps in the epidermis. Using proteomic approaches, SERPINB5 was identified as a DPM1-dependent interaction partner of desmoplakin. Mechanistically, SERPINB5 reduced desmoplakin phosphorylation at serine 176, which was required for strong intercellular adhesion. These results uncover a novel role of the DPM complex in connecting desmosomal adhesion with epidermal differentiation. [ABSTRACT FROM AUTHOR]

In this study, an internal fingerprint-guided epidermal thickness of fingertip skin is proposed for optical image encryption based on optical coherence tomography (OCT) combined with U-Net architecture of a convolutional neural network (CNN). The epidermal thickness of fingertip skin is calculated by the distance between the upper and lower boundaries of the epidermal layer in cross-sectional optical coherence tomography (OCT) images, which is segmented using CNN, and the internal fingerprint at the epidermis–dermis junction (DEJ) is extracted based on the maximum intensity projection (MIP) algorithm. The experimental results indicate that the internal fingerprint-guided epidermal thickness is insensitive to pressure due to normal correlation coefficients and the encryption process between epidermal thickness maps of fingertip skin under different pressures. In addition, the result of the numerical simulation demonstrates the feasibility and security of the encryption scheme by structural similarity index matrix (SSIM) analysis between the original image and the recovered image with the correct and error keys decryption, respectively. The robustness is analyzed based on the SSIM value in three aspects: different pressures, noise attacks, and data loss. Key randomness is valid by the gray histograms, and the average correlation coefficients of adjacent pixelated values in three directions and the average entropy were calculated. This study suggests that the epidermal thickness of fingertip skin could be seen as important biometric information for information encryption. [ABSTRACT FROM AUTHOR]

An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process. [ABSTRACT FROM AUTHOR]

[Display omitted] Healable electronic skins, an essential component for future soft robotics, implantable bioelectronics, and smart wearable systems, necessitate self-healable and pliable materials that exhibit functionality at intricate interfaces. Although a plethora of self-healable materials have been developed, the fabrication of highly conformal biocompatible functional materials on complex biological surfaces remains a formidable challenge. Inspired by regenerative properties of skin, we present the self-assembled transfer-printable liquid metal epidermis (SALME), which possesses autonomous self-healing capabilities at the oil–water interface. SALME comprises a layer of surfactant-grafted liquid metal nanodroplets that spontaneously assemble at the oil–water interface within a few seconds. This unique self-assembly property facilitates rapid restoration (<10 s) of SALME following mechanical damage. In addition to its self-healing ability, SALME exhibits excellent shear resistance and can be seamlessly transferred to arbitrary hydrophilic/hydrophobic curved surfaces. The transferred SALME effectively preserves submicron-scale surface textures on biological substrates, thus displaying tremendous potential for future epidermal bioelectronics. [ABSTRACT FROM AUTHOR]

Rapid increase in body surface area of growing zebrafish larvae (Danio rario) is partially accomplished by asynthetic fission of superficial epithelial cells (SECs) of the skin. There are two cycles of this atypical form of cell division which is unaccompanied by DNA replication; resulting in cells with a variable DNA content. Here, electron microscopy of basal epithelium cells that give rise to these SECs in zebrafish larvae shows aggregation of mitochondria around the nucleus and the formation of nucleus–mitochondria membrane contact sites. Membrane aggregates appear in the lumen of the nuclear envelope at these sites of membrane contact in some cells, suggesting lipid turnover in this vicinity. As the epithelial cells mature and stratify, the mitochondria are engulfed by extensions arising from the nuclear envelope. The mitochondrial outer membrane fragments and mitochondria fuse with the nuclear envelope and parts of the endoplasmic reticulum. Other organelles, including the Golgi apparatus, progressively localize to a central region of the cell and lose their integrity. Thus, asynthetic fission is accompanied by an atypical pattern of organelle destruction and a prelude to this is the formation of nucleus–mitochondria membrane contact sites. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate secondary intention wound healing in the horse's limbs when treated with the synthetic epidermis spray (Novacika®, Cohesive S.A.S, France) or with a standard bandaging technique. Methods: Six Standardbred mares were included in the study. Four 2.5 x 2.5 cm full-thickness skin wounds were created on each thoracic limb. Two wounds were located on the dorsoproximal aspect of the cannon bone and the other two at the dorsoproximal aspect of the fetlock. Six hours after creation, wounds were randomly treated with synthetic epidermis spray or standard bandaging. The wounds were assessed every 4 days by gross visual assessment and using a 3D imaging camera. Analysis was performed with a 3D imaging application. Results: Out of 46 wounds, 22 showed exuberant granulation tissue and were part of the standard bandaging group. Whether the wounds were treated with synthetic epidermis spray or standard bandaging, the time for healing was the same. Conclusion: The synthetic epidermis spray studied in this model has allowed healing without the production of exuberant granulation tissue but did not reduce the median wound healing time compared to a standard bandaging technique. The synthetic epidermis spray is potentially an interesting alternative for the management of secondary intention wound healing of superficial and non-infected distal limb wounds in adult horses on economical and practical aspects. However, all statistical inference (p-values especially) must be interpreted with caution, given the size of the sample. [ABSTRACT FROM AUTHOR]

Cutaneous evaporative water loss (CEWL) makes up a significant portion of total evaporative water loss in many terrestrial vertebrates. CEWL changes on evolutionary and acclimatory timescales in response to temperature and humidity. However, the lability of CEWL on acute timescales is unknown. To examine this, we increased or decreased body temperatures of western fence lizards (Sceloporus occidentalis) over a 15-min period while continuously recording CEWL with a handheld evaporimeter. CEWL increased in response to heating and decreased in response to cooling on the order of seconds. However, CEWL was different between heating and cooling groups at a common body temperature. We observed the same positive relationship between CEWL and body temperature, as well as the difference in CEWL between treatments, for deceased lizards that we opportunistically measured. However, deceased lizards had more extreme CEWL values for any given body temperature and treatment. Overall, our results suggest that both structural traits and active physiological processes likely influence the rates and plasticity of CEWL. [ABSTRACT FROM AUTHOR]