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Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Microtubules (MTs) are dynamic components of the cytoskeleton and play essential roles in morphogenesis and maintenance of tissue and cell integrity. Despite recent advances in understanding MT ultrastructure, organization, and growth control, how cells regulate MT organization at the cell cortex remains poorly understood. The EFA-6/EFA6 proteins are recently identified membrane-associated proteins that inhibit cortical MT dynamics. Here, combining visualization of endogenously tagged C. elegans EFA-6 with genetic screening, we uncovered tubulin-dependent regulation of EFA-6 patterning. In the mature epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR). We further show the EFA-6 IDR is sufficient to form biomolecular condensates in vitro. In screens for mutants with altered GFP::EFA-6 localization, we identified a novel gain-of-function (gf) mutation in an α-tubulin tba-1 that induces ectopic EFA-6 foci in multiple cell types. tba-1(gf) animals exhibit temperature-sensitive embryonic lethality, which is partially suppressed by efa-6(lf), indicating the interaction between tubulins and EFA-6 is important for normal development. TBA-1(gf) shows reduced incorporation into filamentous MTs but has otherwise mild effects on cellular MT organization. The ability of TBA-1(gf) to trigger ectopic EFA-6 foci formation requires β-tubulin TBB-2 and the chaperon EVL-20/Arl2. The tba-1(gf)-induced EFA-6 foci display slower turnover, contain the MT-associated protein TAC-1/TACC, and require the EFA-6 MTED. Our results reveal a novel crosstalk between cellular tubulins and cortical MT regulators in vivo.

IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown of TCF4 in human keratinocytes (KCs) increased IL17C. IL-17C stimulation of KCs (along with IL-17A and TNF-α stimulation) decreased TCF4 and increased NFKBIZ and ZC3H12A expression in an IL-17RA/RE-dependent manner, thus creating a feedback loop. ZC3H12A (MCPIP1/Regnase-1), a transcriptional immune-response regulator, also increased following TCF4 siRNA knockdown, and siRNA knockdown of ZC3H12A decreased NFKBIZ, IL1B, IL36G, CCL20, and CXCL1, revealing a proinflammatory role for ZC3H12A. Examination of lesional skin from the KC-Tie2 inflammatory dermatitis mouse model identified decreases in TCF4 protein concomitant with increases in IL-17C and Zc3h12a that reversed following the genetic elimination of Il17c, Il17ra, and Il17re and improvement in the skin phenotype. Conversely, interference with Tcf4 in KC-Tie2 mouse skin increased Il17c and exacerbated the inflammatory skin phenotype. Together, these findings identify a role for TCF4 in the negative regulation of IL-17C, which, alone and with TNF-α and IL-17A, feed back to decrease TCF4 in an IL-17RA/RE-dependent manner. This loop is further amplified by IL-17C-TCF4 autocrine regulation of ZC3H12A and IL-17C regulation of NFKBIZ to promote self-sustaining skin inflammation.

Tik Tok is an emerging social media platform that provides a novel opportunity for health practitioners such as dermatologists to disseminate accurate health information.

The avian skin is a vital barrier against external effects and undergoes modification to adapt to the different ecosystems. The current study focused on the comprehensive study of the scaly shank skin of aquatic birds, Egyptian Balady Duck (EBD) as well as terrestrial birds, Broad Breasted White Turkey (BBWT) via gross anatomy, histology, and scanning electron microscopy with ED-XRF analysis. The shank skin color was yellow to black in EBD and creamy-white in BBWT. Gross anatomy exhibited two types of scales around the shank: scute and scutella scales in EBD and four types: scute, scutella, reticula, and cancella (interstitial) scales in BBWT. Most scales were non-overlapped and separated by sulci in both birds except those on the dorsum of the shank of BBWT. SEM of the descaled skin revealed an irregular surface due to keratinocytes defining a polygonal texture in EBD and Langerhans cells (a large oval-shaped cell body with abundant long projections) attached to neighboring keratinocytes in BBWT. Histologically, the epidermal and dermal layers varied among the different skin aspects of the shanks of both birds. Langerhans cells were seen within the basal cell layer of the stratum germinativum and collagen fibers of the dermal stratum superficiale. Melanocytes were observed in the stratum basale in EBD. In both birds, abundant telocytes and fibroblasts were distributed within the dermal layers, with excessive adipose tissue in the dermis of the shank skin of EBD. According to the results of the ED-XRF analysis of the scaly shank skin, elements and oxides were present in both species. In conclusion, the findings of the present study reflect the correlations between the functional morphology of shank skin and the bird habitats. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, increased hand hygiene practices using water, soap and hand disinfectants, became prevalent, particularly among frontline workers. This study investigates the impact of these practices on the skin's ability to retain the allergenic metals nickel, cobalt, and chromium. The study constitutes three parts: (I) creating an impaired skin barrier, (II) exposing treated and untreated skin to nickel alone, and (III) in co-exposure with cobalt and chromium. Methods: Using full-thickness skin from stillborn piglets, in vitro experiments were conducted to assess retention of metals in skin at conditions mimicking intense hand hygiene practices. Treatment of skin with varying concentrations of sodium lauryl sulphate (SLS), to impair its barrier integrity was assessed. This was followed by exposure of treated and untreated skin to the metals, that were dissolved in Milli-Q water, 0.5% SLS, and ethanol respectively. Results: Results showed that pre-treatment with 5% SLS impaired the skin barrier with regards to the measure of trans epidermal water loss (TEWL). Metal amounts retained in the skin were generally higher in treated than untreated skin. The highest amounts of metal retained in skin were observed for exposure to nickel in ethanol. Co-exposure to nickel, cobalt, and chromium in 0.5% SLS resulted in the highest amounts of total metal retention. Conclusions: The in vitro findings highlight the increased risk of metal retention in skin due to an impaired barrier. The SLS concentration used in the current study corresponds to those used in many hand hygiene products. Hence, occupational settings with frequent exposure to water, soap and disinfectants need to consider protective measures not only for the irritant exposures themselves but also simultaneous exposure to allergenic metals. [ABSTRACT FROM AUTHOR]

The epidermis is a stratified epithelium that functions as the first line of defense against pathogenic invasion and acts as a barrier preventing water loss. In this study, we aimed to decipher the role of 14‐3‐3ε in the development of the epidermis. We report that loss of 14‐3‐3ε in the epidermis of juvenile and adult mice reduces cell division in the basal layer and increases the percentage of cells with multiple centrosomes, leading to a reduction in the thickness of the basal and stratified layers. We also demonstrate a decrease in the expression of differentiation markers, although no gross morphological defects in the skin or adverse effects on the survival of the mice were observed. These results suggest that loss of 14‐3‐3ε in the epidermis may lead to defects in proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Enfortumab vedotin (EV), a nectin‐4‐binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV‐induced cutaneous eruption. A 58‐year‐old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV‐induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV‐induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV‐induced eruption, which may inform dermatologic and oncologic management. [ABSTRACT FROM AUTHOR]

In this review we discuss how the mammalian interfollicular epidermis forms during development, maintains homeostasis, and is repaired following wounding. Recent studies have provided new insights into the relationship between the stem cell compartment and the differentiating cell layers; the ability of differentiated cells to dedifferentiate into stem cells; and the epigenetic memory of epidermal cells following wounding. [Display omitted] • Switch between planar and perpendicular cell divisions during development. • Epidermal signalling is integrated at the cellular and supracellular levels. • Epigenetic environmental and lineage memory of wounding. [ABSTRACT FROM AUTHOR]

Terminal differentiation of epithelial cells is critical for the barrier function of the skin, the growth of skin appendages, such as hair and nails, and the development of the skin of amniotes. Here, we present the hypothesis that the differentiation of cells in the embryonic periderm shares characteristic features with the differentiation of epithelial cells that support the morphogenesis of cornified skin appendages during postnatal life. The periderm prevents aberrant fusion of adjacent epithelial sites during early skin development. It is shed off when keratinocytes of the epidermis form the cornified layer, the stratum corneum. A similar role is played by epithelia that ensheath cornifying skin appendages until they disintegrate to allow the separation of the mature part of the skin appendage from the adjacent tissue. These epithelia, exemplified by the inner root sheath of hair follicles and the epithelia close to the free edge of nails or claws, are referred to as scaffolding epithelia. The periderm and scaffolding epithelia are similar with regard to their transient functions in separating tissues and the conserved expression of trichohyalin and trichohyalin-like genes in mammals and birds. Thus, we propose that parts of the peridermal differentiation program were coopted to a new postnatal function during the evolution of cornified skin appendages in amniotes. [Display omitted] • The periderm prevents adhesion of adjacent stratified epithelia during development • Cornified skin appendages require scaffolding epithelia for morphogenesis • The inner root sheath of the hair follicle is an example a scaffolding epithelium • Scaffoldin is a marker of the periderm and scaffolding epithelia of birds • Trichohyalin is the mammalian homolog of scaffoldin [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the body and forms the interface between the body and the environment. Its structure is highly adapted to protect the body from many forms of noxious agents, to maintain homeostasis in several physiologic domains and to allow the individual to appreciate various modalities of sensation. The skin is divided into three layers – the epidermis, dermis and hypodermis (or subcutaneous tissue). The epidermis is a continually regenerating structure formed mainly from keratinocytes which account for the majority of cells in the epidermis. The pigment melanin, produced in the melanocyte cells of the epidermis is a major factor in determining skin colour. The dermis supports and gives strength and flexibility to the epidermis. It contains multiple blood vessels, lymphatics and nerves within its connective tissue architecture. The hypodermis is composed of various amounts of subcutaneous fat which plays a role in thermoregulation and water storage. It is essential that surgeons have a good knowledge of the structure of skin in order to choose the optimum site for surgical incisions, to understand the best methods of wound closure and to anticipate potential problems with wound healing. Furthermore, recognizing the role of specialist advice from plastic, reconstructive, or trauma surgeons is crucial for managing wounds that are complex, large, involve underlying structures, or are located on exposed skin such as the face and neck. [ABSTRACT FROM AUTHOR]

Forest trees generate substantial quantities of organic carbon, recognized as a renewable and economically viable resource for applications in bioenergy and industry. This study specifically focuses on xylan, a major hemicellulose component in poplar, and on the role of PtrPARVUS2—a member of the glycosyltransferase 8 family genes involved in xylan biosynthesis. PtrPARVUS2 is hypothesized to exhibit tissue-specific activity, and here we assessed its promoter via bioinformatic analysis, revealing motifs associated with responsiveness to hormones including Gibberellic Acid (GA), Methyl Jasmonate (MeJA), Auxin, and Abscisic Acid (ABA), among others. Treatment with hormones, including ABA, 1-naphthaleneacetic acid, a synthetic auxin, MeJA, and GA, demonstrated a swift inhibition of PtrPARVUS2 transcription. Analysis of expression patterns in wildtype trees indicated heightened expression in vascular tissues, particularly the bark. Transgenic lines expressing Enhanced Green Fluorescent Protein and β-glucuronidase under the control of the PtrPARVUS2 promoter confirmed tissue-specific activity, particularly in guard cells, stem epidermis, and developing xylem. These results offer understanding into the potential functions of PtrPARVUS2 in terms of phytohormone response and the formation of guard cell walls. The investigation introduces a valuable promoter for specific biotechnological applications in guard cells and stem epidermal cells. Additional research is required to elucidate the precise regulatory mechanisms of PtrPARVUS2 in the future.Key message: This study uncovers tissue-specific and hormone-responsive activity of the PtrPARVUS2 promoter, providing insights into xylan biosynthesis and offering a valuable tool for targeted poplar guard cells and stem epidermis expression. [ABSTRACT FROM AUTHOR]

Because the earthworm tegument represents their first barrier against environmental aggressions, we hypothesised that substrate-induced changes in earthworm growth would also alter the morphology of this protective layer. Therefore, a histological and morphometric study was performed on Eisenia fetida specimens that have been grown in five different organic residues: cow manure, horse manure, grape marc, coffee grounds, and a mixture of coffee grounds and cooking oil. The results showed that, across all treatments, both cuticle and epidermis were significantly thicker in the pre-clitellar region than after the clitellum, attributed to the fact that the former region is responsible for breaking up the soil. Notably, the growing media significantly altered the thickness of these two integumentary layers, and the greatest thicknesses were measured in grape marc and in the mixture coffee grounds + cooking oil, which makes them suitable organic residues for vermicomposting. By contrary, a significant epidermal thinning was observed when growing on coffee grounds alone, clearly indicating that it is a hostile environment for earthworms. Overall, these results reveal that tegument thickness can be used not only as a trait indicator of substrate quality but also of earthworm welfare, and it should be integrated in future toxicity assessment and captive breeding guidelines. [ABSTRACT FROM AUTHOR]

GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to enhanced yellow fluorescent protein (EYFP) show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent with tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell type differentiation of the epidermis. [ABSTRACT FROM AUTHOR]

Stomatal pores in leaves mediate CO2 uptake into the plant and water loss via transpiration. Most plants are hypostomatous with stomata present only in the lower leaf surface (abaxial epidermis). Many herbs, including the model plant Arabidopsis, have substantial numbers of stomata also on the upper (adaxial) leaf surface. Studies of stomatal development have mostly focused on abaxial stomata and very little is known of adaxial stomatal formation. We analysed the role of leaf number in determining stomatal density and stomatal ratio, and studied adaxial and abaxial stomatal patterns in Arabidopsis mutants deficient in known abaxial stomatal development regulators. We found that stomatal density in some genetic backgrounds varies between different fully expanded leaves, and thus we recommend using defined leaves for analyses of stomatal patterning. Our results indicate that stomatal development is at least partly independently regulated in adaxial and abaxial epidermis, as (i) plants deficient in ABA biosynthesis and perception have increased stomatal ratios, (ii) the epf1epf2 , tmm , and sdd1 mutants have reduced stomatal ratios, (iii) erl2 mutants have increased adaxial but not abaxial stomatal index, and (iv) stomatal precursors preferentially occur in abaxial epidermis. Further studies of adaxial stomata can reveal new insights into stomatal form and function. [ABSTRACT FROM AUTHOR]

ABSTRACT Post‐inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti‐melanogenic and anti‐inflammatory effects of Bay 11‐7082, an NF‐κB inhibitor, using small‐molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated in vitro and ex vivo in epidermis‐humanized mice using melanin content, RT‐PCR, and immunoblotting. Bay 11‐7082 suppressed proinflammatory cytokines and ameliorated 2,4‐dinitrofluorobenzene (DNFB)‐induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11‐7082 was attributed to the reduction of MITF, which was induced by extracellular signal‐regulated kinase activation. Bay 11‐7082 reduced epidermal melanin accumulation in UVB‐stimulated ex vivo human epidermis as well as in the ear and tail skin of K14‐stem cell factor (SCF) transgenic mice. Topical administration of Bay 11‐7082 improved PIH on day 35 in the post‐DNFB dorsal skin of K14‐SCF transgenic mice. In conclusion, Bay 11‐7082 can be considered a promising candidate for the development of a preventive topical agent for PIH. [ABSTRACT FROM AUTHOR]

This article presents the results of a study of the influence of radionuclide and chemical pollution on the morphological and anatomical parameters of Calamagróstis epigéjos plants growing in the territory of "Degelen" at the Semipalatinsk Test Site (STS). Quantitative data of morphological and anatomical parameters are given, and the content of radionuclides and toxic elements in samples of plants obtained. Statistical processing of the obtained data was conducted. The results revealed that elevated concentrations of radionuclides 137Cs and 90Sr, and the calculated absorbed dose, do not have effects on plants. Changes in the anatomical parameters of leaves and stems were observed at elevated concentrations of the elements: for leaves—Al, Pb, Sr, U, Ni, Rb, Sm; for stems—Al, Cr, Cd, U, Cu, Be, Ni, Sm, Fe. The mesophyll of the leaves and the epidermis of the stems were the most exposed to toxic elements. The data of the anatomical parameters are recommended to be used as indicative parameters of plants grown in chemically contaminated areas. [ABSTRACT FROM AUTHOR]

Single‐cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell‐intrinsic and ‐extrinsic stressors. With an atlas of single‐cell RNA‐sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging. A skin‐specific cellular senescence gene set, termed SenSkin™, was curated and confirmed to be elevated in the context of photoaging, chronological aging, and non‐replicating CDKN1A+ (p21) cells. In the epidermis, senescent melanocytes were associated with elevated melanin synthesis, suggesting haphazard pigmentation, while in the dermis, senescent reticular dermal fibroblasts were associated with decreased collagen and elastic fiber synthesis. Spatial analysis revealed the tendency for senescent cells to cluster, particularly in photoaged skin. This work proposes a strategy for characterizing age‐related skin dysfunction through the lens of cellular senescence and suggests a role for senescent epidermal cells (i.e., melanocytes) and senescent dermal cells (i.e., reticular dermal fibroblasts) in age‐related skin sequelae. [ABSTRACT FROM AUTHOR]

Persistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro‐inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge‐like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4‐arm PEG‐NH2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP‐1. Enrichment of MCP‐1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP‐1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard‐of‐care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

One of the rarest and most unusual iguanas on the planet is the Galápagos pink land iguana (Conolophus marthae). There have been a number of hypotheses on the source of their pink coloration, including that the colour is from blood and a relative lack of dermal pigmentation. We obtained full thickness skin biopsies of three species and compared tissue from darkly pigmented areas and lightly pigmented surfaces. "Pink" areas of pink iguanas are devoid of pigment cells (e.g. melanophores) and the dermal tissue is rich with aggregates of confluent capillaries. This was in sharp contrast to the minimally vascular (only capillaries were observed) dermal areas of the marine and yellow iguanas. The dermal stratum laxum of every biopsy site contained melanophores except for the pink skin of pink iguanas. Interestingly, marine iguanas have a much thicker epidermal stratum germinativum/granulosum, between 2 and 10 cells thick depending on location, compared to the thinner epidermal stratum germinativum/granulosum of land iguanas (one to three cells thick with most areas possessing just one or two cell layers). These microscopic differences might reflect differences in habitat and ecology of the three species. [ABSTRACT FROM AUTHOR]

Simple Summary: The skin microclimate can be defined as the relationship between temperature and moisture of the skin surface, being considered a risk factor for the development of pressure injuries. The objective was to evaluate the effect of pressure loading on skin temperature and moisture in the heel region of healthy adults. The study was performed at the University of Passo Fundo, Brazil, in October 2022. Ten individuals were evaluated. The pressure loading leads to a decrease in temperature and changes the skin moisture of the heels of healthy individuals. Recent studies emphasize the significance of skin microclimate in the prevention of pressure injuries (PI). The objective was to evaluate the effect of pressure loading on skin temperature and moisture in the heels of healthy adults. This is a before-and-after study performed at Brazil, in October 2022. Skin temperature (°C) was measured by an infrared digital thermometer, and skin moisture (%) using electrical bioimpedance. Ten individuals/twenty heels were evaluated. The average temperature of the right and left heel was the same at baseline (27.2 °C). It was recognized that after 30 min of pressure loading on the heels, there was a decrease in temperature, and after 15 min of pressure offloading, the temperature decreased again. It was found that at t0, the moisture of the right heel (12.6%) was lower than the left heel (15.6%). The median moisture in the right heel increased from t0 to t1 and decreased in t2, while in the left heel, there was a small variation of the median from t0 to t1, as well as to t2. The pressure loading leads to a decrease in temperature and changes the skin moisture of the heels of healthy individuals. [ABSTRACT FROM AUTHOR]

Aseptic pustulosis involves inflammatory skin conditions with nonbacterial pustules on erythema, accompanied by neutrophil and eosinophil infiltration in the epidermis. Dysregulation of the interleukin (IL)-36 pathway leads to neutrophil aggregation and pustule formation. Variants in IL36RN , CARD14 , AP1S3 , MPO , SERPINA3 and BTN3A3 have been identified in generalized pustular psoriasis (GPP) in the past. Some patients with acrodermatitis continua of Hallopeau (ACH), palmoplantar pustulosis and acute generalized exanthematous pustulosis (AGEP) also exhibit mutations in IL36RN , CARD14 and AP1S3 , albeit with regional and population-specific variations. This study aims to explore a shared genetic foundation among those with aseptic pustulosis. We performed Sanger sequencing on six genes in 126 patients with aseptic pustulosis. Genetic analysis identified IL36RN variants strongly associated with ACH, AGEP and subcorneal pustular dermatosis (SPD). Immunohistochemistry revealed elevated inflammatory cytokines in all subtypes. This study establishes a significant association between IL36RN variants and ACH, AGEP and SPD, emphasizing the IL-1/IL-36–chemokine–neutrophil axis as a common pathogenic mechanism. Targeting this axis holds promise for therapeutic interventions for aseptic pustulosis. [ABSTRACT FROM AUTHOR]

Neurons are highly polarized cells with dendrites and axons. Dendrites, which receive sensory information or input from other neurons, often display elaborately branched morphologies. While mechanisms that promote dendrite branching have been widely studied, less is known about the mechanisms that restrict branching. Using the nematode Caenorhabditis elegans , we identify rabr-1 (for Rab - related gene 1) as a factor that restricts branching of the elaborately branched dendritic trees of PVD and FLP somatosensory neurons. Animals mutant for rabr-1 show excessively branched dendrites throughout development and into adulthood in areas where the dendrites overlay epidermal tissues. Phylogenetic analyses show that RABR-1 displays similarity to small GTPases of the Rab - type, although based on sequence alone, no clear vertebrate ortholog of RABR-1 can be identified. We find that rabr-1 is expressed and can function in epidermal tissues, suggesting that rabr-1 restricts dendritic branching cell-nonautonomously. Genetic experiments further indicate that for the formation of ectopic branches rabr-1 mutants require the genes of the Menorin pathway, which have been previously shown to mediate dendrite morphogenesis of somatosensory neurons. A translational reporter for RABR-1 reveals a subcellular localization to punctate, perinuclear structures, which correlates with endosomal and autophagosomal markers, but anticorrelates with lysosomal markers suggesting an amphisomal character. Point mutations in rabr-1 analogous to key residues of small GTPases suggest that rabr-1 functions in a GTP-bound form independently of GTPase activity. Taken together, rabr-1 encodes for an atypical small GTPase of the Rab - type that cell-nonautonomously restricts dendritic branching of somatosensory neurons, likely independently of GTPase activity. [ABSTRACT FROM AUTHOR]

Background: Conspicuous facial pores are benign but represent a cosmetic concern for men and women. Recent works described dermal and epidermal impairments as clinical causes of enlarged pores. Morphological modifications of skin at the site of pores were associated with collagen density loss, possible alteration of extracellular matrix and abnormal differentiation of keratinocytes. Aims: A composition containing mannose‐6‐phosphate (Active Complex) was designed to address these different aspects of pore enlargement. In vitro and ex vivo evaluations were conducted in different models mimicking disturbance of dermal and epidermal functions. The pore refining activity of Active Complex was assessed in two clinical trials studying a Caucasian women cohort and an Asian men cohort. Results: At the dermal level, Active Complex upregulated collagen I and decorin synthesis, and genes encoding collagens I, III, V, VII, XVII; suggesting its ability to favor collagen fiber organization and anchorage. The downregulation of matrix metalloprotease, involved in extracellular matrix degradation, reinforced the protective effect of Active Complex in the dermis. Active Complex down modulated differentiation markers in keratinocytes as well as genes involved in cell renewal. Study of reconstructed human epidermis modeling keratinocyte hyperproliferation revealed that Active Complex mitigated two markers of this state: number of nuclei in the stratum corneum and involucrin expression. Clinical trials confirmed the pore refining activity of Active Complex on men and women of different ages and ethnicities; −24% total skin pore area after 56 days of application on women, and −30.2% on men after 7 days. Conclusions: This work demonstrates the interest to target dermal and epidermal modifications described in conspicuous pore area, especially dermis fiber organization, to address this cosmetic concern. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Pododermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal phalanx in the claw capsule. Pressure from the tuberculum flexorium on the sole epidermis and dermis produces hemorrhagic tissue injury and defective horn production appearing as yellow-red, softened claw horn in region 4 of the sole. A model of the MAPK/ERK signal cascade orchestrating epidermal-dermal homeostasis was employed to determine if sterile inflammatory responses are linked to disturbed signal transduction for epidermal homeostasis in sole epidermis and dermis. The objective was to assess shifts in target genes of inflammation, up- and downstream MAPK/ERK signal elements, and targeted genes supporting epidermal proliferation and differentiation. Sole epidermis and dermis were removed from lateral claws bearing lesions of PAHC, medial claws from the same limb and lateral claws from completely normal limbs of multiparous, lactating Holstein cows. The abundance levels of targeted transcripts were evaluated by real-time PCR. Lesion effects were assessed by ANOVA, and mean comparisons were performed with t -tests to assess variations between mean expression in ulcer-bearing or medial claw dermis and epidermis and completely normal lateral claw dermis and epidermis or between ulcer-bearing dermis and epidermis and medial claw dermis and epidermis. The lesions were sterile and showed losses across multiple growth factors, their receptors, several downstream AP1 transcription components, CMYC, multiple cell-cycle and terminal differentiation elements conducted by MAPK/ERK signals and β 4, α 6, and collagen 17A hemidesmosome components. These losses coincided with increased cytokeratin 6, β 1 integrin, proinflammatory metalloproteinases 2 and 9, IL1B and physiologic inhibitors of IL1B, the decoy receptor, and receptor antagonist. Medial claw epidermis and dermis from limbs with lateral claws bearing PAHC showed reductions in upstream MAPK/ERK signal elements and downstream targets that paralleled those in hemorrhagic lesions. Inhibitors of IL1B increased in the absence of real increases in inflammatory targets in the medial claw dermis and epidermis. Losses across multiple signal path elements and downstream targets were associated with negative effects on targeted transcripts supporting claw horn production and wound repair across lesion-bearing lateral claws and lesion-free medial claw dermis and epidermis. It was unclear if the sterile inflammation was causative or a consequence of these perturbations. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disorder characterized by epidermal melanocyte damage, with the typical clinical manifestation of white patches of skin. Keratinocytes, which work in concert with melanocytes to maintain the structural and functional integrity of the skin, are implicated in the progression of vitiligo. Recent studies have reported abnormal keratinocyte proliferation and epidermal thickening in some patients with vitiligo; however, the relationship between these changes and the clinical characteristics of vitiligo remains unclear. We assessed the changes in epidermal thickness in patients with vitiligo and their correlation with clinical characteristics. Compared to the non-lesional skins, the stratum corneum, viable epidermis, and full epidermis in the lesional skins were all significantly thicker. The thickness of the stratum corneum in the head, neck, and trunk was greatly lower than that in the extremities. The thickness of the stratum corneum in the sun-exposed area was higher than that in the sun-protected area, whereas the thickness of the viable epidermis decreased. In conclusion, our study found that the epidermis in the lesional skins of patients with vitiligo was significantly thickened, especially in the sun-exposed areas and extremities. [ABSTRACT FROM AUTHOR]

The primary line of defense against pathogens from the environment is often fish epidermis tissue. Nevertheless, little is understood about the physiological mechanisms that underlie the non-specific and/or specific protection that these cells can offer. The exact nature of the relationship between the evolution of ostariophysan fish club cells and chemical warning signals is still unknown and controversial. Fish epidermis layer cells comprise mucus cells, lymphocytes, macrophage cells, cuboidal and squamous epithelial cells, and cells specific to certain fish species. Club cells, also called "alarm cells," are chemical alarms that sound in the event of a potentially hazardous scenario. These cells will burst in the presence of a predator, releasing pheromones that, if the skin is physically damaged, trigger an avoidance and terror reaction. In sturgeon larvae, mucus cells were visible in week 1, but club cells did not appear until week 4. Due to their later development during ontogenesis and after wounding, club cells may not have as much of a protective effect during wound healing as filament or mucus cells. Club cells are mostly found in the epidermis of the skin, and it is thought that when they work in tandem with mucus and goblet cells to fight infections, they serve as the body's first line of defense. [ABSTRACT FROM AUTHOR]

There is growing interest in the roles of temperature, epidermal hydration (EH) and pain in pressure ulcer (PU) development. Investigating correlations between these measures and sub‐epidermal moisture (SEM) will address this knowledge deficit. A prospective observational study enrolled 60 surgical patients from February to November 2021. SEM, temperature, EH and pain were assessed using a SEM scanner, thermography imaging, skin hydration device and numeric pain intensity scale, respectively. Measurements were taken at the sacrum, both heels and a control site, before and after surgery for 3 days. Data were analysed using Pearson or Spearman's correlation. Of the participants, 50% were male with a mean age of 58 years (±13.46). Low positive/negative correlations between SEM and temperature were found at the sacrum. However, after removing outliers, these results were not statistically significant. Other sites and follow‐up days showed negligible correlations. No evidence of a correlation, to low correlations between SEM and EH were observed, but unreliable due to little variation in EH at the heels. Pain showed negligible correlations with SEM. This study did not find consistent evidence of a correlation between SEM, temperature, EH and pain, highlighting the unreliability of temperature and EH for early PU detection. Post‐operative pain may also confound accurate pain assessments. [ABSTRACT FROM AUTHOR]

Tardigrades possess the ability to enter an almost completely dehydrated state, anhydrobiosis. The CAHS (cytosolic abundant heat‐soluble) protein family has been identified as one of the anhydrobiosis‐related proteins. In particular, CAHS3 protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus, shows heat‐solubility and reversible condensation and is one of the most highly expressed among the CAHS paralogs. A recently developed tardigrade‐specific vector showed tissue‐specific expression of RvCAHS3 most pronounced in the epidermis in vivo, contrary to the idea that anhydrobiotic genes are uniformly expressed in all tardigrade cells. In this study, we investigated the regulation of RvCAHS3 gene expression through in vivo expression experiments using tardigrade vectors with a series of truncated upstream regions coupled with in silico analysis to identify the anhydrobiosis‐related genes that are expressed under the same regulatory system as RvCAHS3. As a result, the 300–350 bp region upstream of RvCAHS3 is critical for regulating gene expression in tardigrade vector experiments, and three motifs conserved between two species of anhydrobiotic tardigrades were identified within a 500 bp region directly upstream of RvCAHS3 start codon. These motifs, which have also been identified upstream of other CAHS genes, could be associated with the regulatory system of anhydrobiosis‐related genes in tardigrades. [ABSTRACT FROM AUTHOR]

Background: Epidermal remodeling and hypertrophy are hallmarks of skin fibrotic disorders, and keratinocyte to mesenchymal (EMT)-like transformations drive epidermis alteration in skin fibrosis such as keloids and hypertrophic scars (HTS). While phosphodiesterase 4 (PDE4) inhibitors have shown effectiveness in various fibrotic disorders, their role in skin fibrosis is not fully understood. This study aimed to explore the specific role of PDE4B in epidermal remodeling and hypertrophy seen in skin fibrosis. Methods: In vitro experiments examined the effects of inhibiting PDE4A-D (with Roflumilast) or PDE4B (with siRNA) on TGFβ1-induced EMT differentiation and dedifferentiation in human 3D epidermis. In vivo studies investigated the impact of PDE4 inhibition on HOCl-induced skin fibrosis and epidermal hypertrophy in mice, employing both preventive and therapeutic approaches. Results: The study found increased levels of PDE4B (mRNA, protein) in keloids > HTS compared to healthy epidermis, as well as in TGFβ-stimulated 3D epidermis. Keloids and HTS epidermis exhibited elevated levels of collagen Iα1, fibronectin, αSMA, N-cadherin, and NOX4 mRNA, along with decreased levels of E-cadherin and ZO-1, confirming an EMT process. Inhibition of both PDE4A-D and PDE4B prevented TGFβ1-induced Smad3 and ERK1/2 phosphorylation and mesenchymal differentiation in vitro. PDE4A-D inhibition also promoted mesenchymal dedifferentiation and reduced TGFβ1-induced ROS and keratinocyte senescence by rescuing PPM1A, a Smad3 phosphatase. In vivo, PDE4 inhibition mitigated HOCl-induced epidermal hypertrophy in mice in both preventive and therapeutic settings. Conclusions: Overall, the study supports the potential of PDE4 inhibitors, particularly PDE4B, in treating skin fibrosis, including keloids and HTS, shedding light on their functional role in this condition. [ABSTRACT FROM AUTHOR]

Introduction With similar prevalence to injuries from fires, stings, and natural disasters, soft tissue injuries may occur from fireworks, industrial accidents, or other explosives. Surgeons are less familiar with treating high-velocity penetration from small debris, which may increase the chance of infection and subsequent fatality. Penetration risk curves have been developed to predict V50, the velocity with 50% probability of penetration, for various sized projectiles. However, there has been limited research using nonmetallic materials to achieve lower density projectiles less than 1 g cm−2, such as sand or rocks. Material and Methods To emulate the size and density of these energized particles, 14 ball bearings of stainless steel, silicon nitride, or Delrin acetal plastic ranging from 1.59 mm (1/16") to 9.53 mm (3/8") with sectional densities between 0.3 g cm−2 and 5  g cm−2 were launched toward porcine legs at a range of velocities to determine the penetration thresholds. High-speed videography was captured laterally at 40 kHz and impact velocity was captured using a physics-based tracking software. A generalized linear model with repeated measures and a logit link function was used to predict probability of penetration for each projectile. A total of 600 impacts were conducted to achieve at least 15 penetrating impacts for each projectile over a range of velocities. Results Higher impact velocities were required to penetrate the skin as sectional density of the projectile decreased, and the relationship between velocity and sectional density exhibited an exponential relationship (V 50, |$ = 184.6*S{D^{ - 0.385}}$|⁠ , R 2 = 0.95) with substantial change for nonlinearity in sectional densities ranging from 0.3 g cm−2 to 1  g cm−2. Compared to previous studies, the empirical relationship was consistent in the linear region (2-5  g cm−2), and novel experimentation filled in the gaps for sectional densities less than 1  g cm−2, which expressed more nonlinearity than previously estimated. For low-density projectiles with diameters of 1.59 (1/16") or 3.18 (1/8"), 32 impacts were lodged into the epidermis but did not penetrate through the dermis; however, penetration was defined as displacement into or through the dermis. Conclusions These experimental results may be used to develop and validate finite element simulations of low-density projectile impacts to address complex, multivariate loading conditions for the development of protective clothing to reduce wounding and subsequent infection rates. [ABSTRACT FROM AUTHOR]

Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin. [ABSTRACT FROM AUTHOR]

The epidermal differentiation complex (EDC) is a cluster of genes that code for protein components of cornified cells on the skin surface of amniotes. Squamates are the most species-rich clade of reptiles with skin adaptations to many different environments. As the genetic regulation of the skin epidermis and its evolution has been characterized for only a few species so far, we aimed to determine the organization of the EDC in a model species of squamates, the common wall lizard (Podarcis muralis). By comparative genomics, we identified EDC genes of the wall lizard and compared them with homologs in other amniotes. We found that the EDC of the wall lizard has undergone a major rearrangement leading to a unique order of three ancestral EDC segments. Several subfamilies of EDC genes, such as those encoding epidermal differentiation proteins containing PCCC motifs (EDPCCC) and loricrins, have expanded by gene duplications. Most of the EDPCCC proteins have cysteine contents higher than 50%, whereas glycine constitutes more than 50% of the amino acid residues of loricrin 1. The extremely biased amino acid compositions indicate unique structural properties of these EDC proteins. This study demonstrates that cornification proteins of the common wall lizard differ from homologous proteins of other reptiles, illustrating the evolutionary dynamics of diversifying evolution in squamates. [ABSTRACT FROM AUTHOR]

Background: The emergence of horizontal neck wrinkles is increasingly becoming a focal point for both cosmetic professionals and clients. Various treatment approaches must be considered to address this issue effectively, owing to its diverse underlying causes. The study explores the potential of utilizing the Endolift laser in conjunction with nanofat injection as a viable treatment option. Methods: Twenty patients with horizontal neck wrinkles involved in the study. Ten patients underwent treatment with a combination of Endolift laser and nanofat injection and 10 patients treated with nanofat injection alone. The participants were monitored for 6 months post‐treatment. Biometric measurements were utilized to assess outcomes, including changes in volume, depth, and area of the wrinkles, skin elasticity, as well as the diameter and density of the epidermis and dermis in the treated area. Skin improvement was evaluated by two independent dermatologists, who compared before and after photos in a blinded manner. Patient satisfaction levels were also documented. Results: The Visioface analysis showed a notable decrease in neck wrinkle depth and area in both groups. However, the group receiving the combination treatment of Endolift laser and nanofat exhibited a significantly greater improvement compared to the group treated with nanofat alone. Skin ultrasonography results demonstrated an increase in thickness and density of the dermis and epidermis in both groups. Particularly, the group treated with Endolift laser‐nanofat displayed significant enhancements in dermis and epidermis density and thickness when contrasted with the nanofat‐only group. Analysis with Cutometer revealed a marked enhancement in skin elasticity in the Endolift‐nanofat treated group in comparison to the nanofat‐only treated group. Furthermore, in the Endolift‐nanofat treated group, a substantial majority (90%) of patients exhibited improvement. Patient evaluations highlighted significant distinctions between the two groups, with 95% of patients in the Endolift‐nanofat treated group demonstrating enhancement. Conclusion: Both methods notably enhance horizontal neck wrinkles; nevertheless, the combination of endolift laser and nanofat seems to be more efficient for treating horizontal neck wrinkles. [ABSTRACT FROM AUTHOR]

Background: Bipolar microneedling radiofrequency (RF) treatment generates different patterns of thermal reactions, depending on the skin impedance and RF treatment parameters, including the frequency, power, conduction time, settings of sub‐pulse packs, and penetrating depth and type of microneedles used. We compared the effect of sequential delivery of 1‐ and 2‐MHz bipolar RF energy to in vivo minipig skin on thermal tissue reaction. Methods: RF treatments at frequencies of 1 and 2 MHz were sequentially delivered to minipigs' skin in vivo. A histological study was performed to analyze RF‐induced skin reactions at 1‐h and at 3‐, 7‐, and 14‐days post‐treatment. Results: The skin specimens demonstrated that the two different frequencies of RF treatment generated mixed patterns of the peri‐electrode coagulative necrosis (PECN) according to the experimental settings and tissue impedance. In the PECN zone, the tissue coagulation induced by the first RF treatment was surrounded by the effect of the later RF treatment at the other RF frequency. In the inter‐electrode non‐necrotic thermal reaction zone, the effect of the latter RF treatment was widespread and deep through the dermis, which had received RF treatment at the other frequency first. The delivery of pulsed‐type RF energy at sub‐pulse packs of 6 or 10 provided effective RF delivery over long conduction time without excessive thermal damage of the epidermis. Nonetheless, by sequential delivery of two different RF frequencies, RF‐induced tissue reactions were found to be markedly enhanced. Conclusion: The sequential delivery of 1‐ and 2‐MHz RF energy induces novel histological patterns of tissue reactions, which can synergistically enhance the thermostimulatory effects of each RF setting. Moreover, variations in patterns of tissue reactions can be generated by regulating the order of frequencies and the number of sub‐pulse packs of RF used. [ABSTRACT FROM AUTHOR]

Objective: This study explores the application of Line‐field Confocal Optical Coherence Tomography (LC‐OCT) imaging coupled with artificial intelligence (AI)‐based algorithms to investigate atopic dermatitis (AD), a common inflammatory dermatosis. Materials and methods: AD acute and chronic lesions (ADL) were compared to clinically healthy‐looking skin (ADNL). LC‐OCT was used noninvasively and in real‐time to image the skin of AD patients during flare‐ups and monitor remissions under topical steroid treatment for 2 weeks. Quantitative parameters were extracted from the images, including morphological and cellular‐level markers of epidermal architecture. A novel cellular‐level parameter, nuclei "atypia," which quantifies the orderliness of epidermal renewal, was used to highlight abnormal maturation processes. Results: Compared to healthy skin, AD lesions exhibited significant increases in both epidermal and stratum corneum (SC) thickness, along with a more undulated dermo‐epidermal junction (DEJ). Additionally, keratinocyte nuclei (KN) were larger, less compact, and less organized in lesional areas, as indicated by the atypia parameter. A higher degree of atypia was observed in chronic lesions compared to acute ones. Following treatment, all the parameters normalized to levels observed in healthy skin within 2 weeks, mirroring clinical improvements. Conclusion: This study provides insights into the quantification of epidermal renewal using a noninvasive imaging technique, highlighting differences between ADL/ADNL and acute/chronic lesions. It also presents the AD treatment mechanism, paving the way for future investigations on AD and other skin barrier function‐related conditions. [ABSTRACT FROM AUTHOR]

Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies. • A novel AAV capsid termed AAVDJK2 was developed and was superior to existing AAVs in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • A novel tissue-specific promotor termed K14 SCP3 promotor was developed and was superior to existing promoters in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • The novel AAV system benefits experimental research and development of new epidermis-targeted gene therapies. [ABSTRACT FROM AUTHOR]

The elongation of Caenorhabditis elegans embryos allows examination of mechanical interactions between adjacent tissues. Muscle contractions during late elongation induce the remodeling of epidermal circumferential actin filaments through mechanotransduction. Force inputs from the muscles deform circumferential epidermal actin filament, which causes them to be severed, eventually reformed, and shortened. This squeezing force drives embryonic elongation. We investigated the possible role of the nonmuscle myosins NMY-1 and NMY-2 in this process using nmy-1 and nmy-2 thermosensitive alleles. Our findings show these myosins act redundantly in late elongation, since double nmy-2(ts); nmy-1(ts) mutants immediately stop elongation when raised to 25°C. Their inactivation does not reduce muscle activity, as measured from epidermis deformation, suggesting that they are directly involved in the multistep process of epidermal remodeling. Furthermore, NMY-1 and NMY-2 inactivation is reversible when embryos are kept at the nonpermissive temperature for a few hours. However, after longer exposure to 25°C double mutant embryos fail to resume elongation, presumably because NMY-1 was seen to form protein aggregates. We propose that the two C. elegans nonmuscle myosin II act during actin remodeling either to bring severed ends or hold them. [ABSTRACT FROM AUTHOR]

Background Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti–vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab. Methods Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months). Results Of the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2 months, respectively (hazard ratio = 0.75, P = .07; statistically significant by study design for P  < .128). Response rate was 23% vs 36% (P = .27), and disease-control rate was 52% vs 73% (P  = .05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19 months. Conclusion Previous phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780) [ABSTRACT FROM AUTHOR]

Aims: To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra‐epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. Methods: Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two‐way mixed‐effects model to evaluate inter‐ and intra‐observer variability. Results: The automated staining system reproduced intra‐epidermal nerve fibre density (IENFD) counts consistent with free‐floating sections (mean ± standard deviation: free‐floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at −0.00005 established non‐inferiority against a margin of −0.4 (p =.08). Specifically, the inter‐class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9–1), indicating excellent agreement between free‐floating and automated methods. The inter‐ and intra‐class coefficient between examiners were both 99% (95% CI: 0.9–0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. Interpretation: Automated immunohistochemistry provides high‐throughput reliable and reproducible intra‐epidermal nerve fibre quantification. This method, although currently proof‐of‐concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies. [ABSTRACT FROM AUTHOR]

The ultrastructure of the leaf epidermis and the localization and content of silicon in epidermal cells of the psammophyte Alyssum desertorum Stapf (Brassicaceae) were investigated using electron microscopy and laser confocal microscopy. The study aimed to examine the effect of flooding on the epidermal structure of the leaves, study the presence, localization, and content of silicon in the epidermal cells and determine whether changes in soil moisture affect the silicon content in the leaf epidermis. Silicon inclusions were observed in trichomes and typical epidermal cells on both leaf surfaces, with varying content depending on the cell type, leaf surface, and conditions growth. Soil flooding was found to influence the leaf epidermis ultrastructure and the silicon content in the epidermal cells of A. desertorum. Trichomes and pavement cells were identified as the main accumulators of silicon inclusions and wax-like structures. These findings suggest that changes in leaf microstructure and silicon content contribute to the normal functioning of psammophyte plants and can be considered signs of plant phenotypic plasticity and adaptive markers depending on water supply conditions. [ABSTRACT FROM AUTHOR]

Haematomas of the lower limb are traumatic wounds that can have serious and often debilitating consequences; especially in the aged. Wound healing may be protracted due to multiple factors including disruptive consumer behaviours from poor cognition from dementia. This case study describes the management of an elderly consumer with dementia in a nursing home who sustained an extensive haematoma that resulted in a complex wound. Wound management was provided under local restrictions imposed by COVID-19. The importance of using holistic wound assessment frameworks and evidence-based approaches to wound management to achieve positive wound healing outcomes are emphasised. [ABSTRACT FROM AUTHOR]

Significance: Aquaporins and ion channels establish and regulate gradients of calcium, sodium, potassium, chloride, water, and protons in the epidermis. These elements have been found to play significant roles in skin biology and wound healing. In this study, we review our understanding of these channels and ion gradients, with a special emphasis on their role in acute wound healing. Recent Advances: Specifically, we assess the temporal and spatial arrangements of ions and their respective channels in the intact skin and during wound and healing to provide a novel perspective of the role of ionic gradients through the various stages of wound healing. Critical Issues: The roles of gradients of ions and channels in wound healing are currently not well understood. A collective analysis of their traits and arrangements in the skin during wound healing may provide a new perspective and understanding of the functionality of gradients of ions and channels in skin biology and wound healing. Future Directions: It is important to elucidate how the gradients of ions and ion channels regulate and facilitate wound healing. A better understanding of the ionic environments may identify novel therapeutic targets and improved strategies to promote wound healing and possibly treat other cutaneous diseases.

Skin expands and regenerates in response to mechanical stretch. This important homeostasis process is critical for skin biology and can be exploited to generate extra skin for reconstructive surgery. Atmospheric oxygen uptake is important in skin homeostasis. However, whether and how cutaneous atmospheric oxygen uptake changes during mechanical stretch remains unclear, and relevant research tools to quantify oxygen flux are limited. Herein, we used the scanning micro-optrode technique (SMOT), a non-invasive self-referencing optical fiber microsensor, to achieve real-time measurement of cutaneous oxygen uptake from the atmosphere. An in vivo mechanical stretch-induced skin expansion model was established, and an in vitro Flexcell Tension system was used to stretch epidermal cells. We found that oxygen influx of skin increased dramatically after stretching for 1 to 3 days and decreased to the non-stretched level after 7 days. The enhanced oxygen influx of stretched skin was associated with increased epidermal basal cell proliferation and impaired epidermal barrier. In conclusion, mechanical stretch increases cutaneous oxygen uptake with spatial-temporal characteristics, correlating with cell proliferation and barrier changes, suggesting a fundamental mechanistic role of oxygen uptake in the skin in response to mechanical stretch. Optical fiber microsensor-based oxygen uptake detection provides a non-invasive approach to understand skin homeostasis.

Abstract The avian skin is a vital barrier against external effects and undergoes modification to adapt to the different ecosystems. The current study focused on the comprehensive study of the scaly shank skin of aquatic birds, Egyptian Balady Duck (EBD) as well as terrestrial birds, Broad Breasted White Turkey (BBWT) via gross anatomy, histology, and scanning electron microscopy with ED-XRF analysis. The shank skin color was yellow to black in EBD and creamy-white in BBWT. Gross anatomy exhibited two types of scales around the shank: scute and scutella scales in EBD and four types: scute, scutella, reticula, and cancella (interstitial) scales in BBWT. Most scales were non-overlapped and separated by sulci in both birds except those on the dorsum of the shank of BBWT. SEM of the descaled skin revealed an irregular surface due to keratinocytes defining a polygonal texture in EBD and Langerhans cells (a large oval-shaped cell body with abundant long projections) attached to neighboring keratinocytes in BBWT. Histologically, the epidermal and dermal layers varied among the different skin aspects of the shanks of both birds. Langerhans cells were seen within the basal cell layer of the stratum germinativum and collagen fibers of the dermal stratum superficiale. Melanocytes were observed in the stratum basale in EBD. In both birds, abundant telocytes and fibroblasts were distributed within the dermal layers, with excessive adipose tissue in the dermis of the shank skin of EBD. According to the results of the ED-XRF analysis of the scaly shank skin, elements and oxides were present in both species. In conclusion, the findings of the present study reflect the correlations between the functional morphology of shank skin and the bird habitats.

Abstract Mammalian wounds leave visible scars, and there are no methods for complete regeneration. However, mouse fetuses regenerate their skin, including epidermal and dermal structures, up to embryonic day (E)13. This regeneration pattern requires the formation of actin cables in the wound margin epithelium; however, the molecular mechanisms are not fully understood. Rac1 alters actin in cells and is involved in the formation of filopodia. We investigated whether actin remodeling and skin regeneration patterns can be reproduced through the regulation of Rac1 signaling. Rac1 expression was downregulated in E13 wounds and upregulated after E15 when scars remained. NSC23766, a Rac1-specific inhibitor, altered actin dynamics at the cell margin from filopodia formation to cable formation and inhibited the migration of mouse epidermal keratinocyte, PAM212, by Rac1 signaling suppression. NSC23766 suppressed Rac1 activity and completely regenerated the fetal mouse wounds, even at E14, by changing actin dynamics. Knocked-out Rac1 transgenic mice experienced delayed epithelialization of wounds with suppressed epidermal migration in adults; however, in fetuses, complete wound regeneration via Rac1 signal suppression was observed. Therefore, Rac1 suppression in the wound epidermis can achieve regenerative wound healing in fetuses and may be a potential candidate for healing scars.

Peucedanum L. (Apiaceae) is broadly distributed in the Old World, and 11 taxa, including five endemic species, have been reported in Korea. In this study, we used scanning electron microscopy to describe petal epidermal cell patterns and evaluated their systematic implications for all Korean Peucedanum species except for one. This included two recently reported endemic species, P. miroense and P. tongkangense, which are closely associated with Heracleum moellendorffii. The epidermal characteristics of the petals, including cell type (papillose conical, papillose knobby rugose, tabular conical, or tabular rugose), anticlinal wall shape (straight, sinuous, or curved), cuticle sculpture (striate or wrinkled), and stomata (presence or absence) were observed. The petal epidermis could be categorized into three types and two subtypes. We concluded that petal epidermal characteristics provide evidence supporting the recent robust phylogeny that suggests the non-monophyly of the genus Peucedanum. In particular, P. japonicum and P. praeruptorum, which are positioned in different clades to the other species in the recent phylogeny, had different types of petal epidermis among the studied species. These petal epidermal micro-characteristics were evaluated as possible consistent parameters for the taxonomic delimitation of species of the genus Peucedanum.

The human body exhibits complex, spatially distributed chemo-electro-mechanical processes that must be properly captured for emerging applications in virtual/augmented reality, precision health, activity monitoring, bionics, and more. A key factor in enabling such applications involves the seamless integration of multipurpose wearable sensors across the human body in different environments, spanning from indoor settings to outdoor landscapes. Here, we report a versatile epidermal body area network ecosystem that enables wireless power and data transmission to and from battery-free wearable sensors with continuous functionality from dry to underwater settings. This is achieved through an artificial near field propagation across the chain of biocompatible, magneto-inductive metamaterials in the form of stretchable waterborne skin patches-these are fully compatible with pre-existing consumer electronics. Our approach offers uninterrupted, self-powered communication for human status monitoring in harsh environments where traditional wireless solutions (such as Bluetooth, Wi-Fi or cellular) are unable to communicate reliably.

Triphenyl phosphate (TPHP) - a widely used organophosphate-based flame retardant - blocks cardiac looping during zebrafish development in a concentration-dependent manner, a phenotype that is dependent on disruption of embryonic osmoregulation and pericardial edema formation. However, its currently unclear whether (1) TPHP-induced effects on osmoregulation are driven by direct TPHP-induced injury to the embryonic epidermis and (2) whether TPHP-induced pericardial edema is reversible or irreversible following cessation of exposure. Therefore, the objectives of this study were to determine whether TPHP-induced pericardial edema is reversible and whether TPHP causes injury to the embryonic epidermis by quantifying the number of DAPI-positive epidermal cells and analyzing the morphology of the yolk sac epithelium using scanning electron microscopy. First, we found that exposure to 5 μM TPHP from 24-72 h post-fertilization (hpf) did not increase prolactin - a hormone that regulates ions and water levels - in embryonic zebrafish, whereas high ionic strength exposure media was associated with elevated levels of prolactin. Second, we found that exposure to 5 μM TPHP from 24-72 hpf did not decrease DAPI-positive epidermal cells within the embryonic epithelium, and that co-exposure with 2.14 μM fenretinide - a synthetic retinoid that promotes epithelial wound repair - from 24-72 hpf did not mitigate the prevalence of TPHP-induced epidermal folds within the yolk sac epithelium when embryos were exposed within high ionic strength exposure media. Finally, we found that the pericardial area and body length of embryos exposed to 5 μM TPHP from 24-72 hpf were similar to vehicle-treated embryos at 120 hpf following transfer to clean water and depuration of TPHP from 72-120 hpf. Overall, our findings suggest that (1) the ionic strength of exposure media may influence the baseline physiology of zebrafish embryos; (2) TPHP does not cause direct injury to the embryonic epidermis; and (3) TPHP-induced effects on pericardial area and body length are reversible 48 h after transferring embryos to clean water.

Objective: 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. Methods: 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. Results: 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. Conclusion: 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]