Thin-film electronic devices can be integrated with skin for health monitoring and/or for interfacing with machines. Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. Therefore, it is necessary to systematically investigate their long-term physiological and psychological effects. As a demonstration of substrate-free electronics, here we show the successful fabrication of inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time, realized with a conductive nanomesh structure. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. The current strategies to treat AD in Japan from the perspective of evidence‐based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice.

Atopic dermatitis is a common inflammatory skin disease caused by interaction of genetic and environmental factors. On the basis of data from a genome-wide association study (GWAS) and a validation study comprising a total of 3,328 subjects with atopic dermatitis and 14,992 controls in the Japanese population, we report here 8 new susceptibility loci: IL1RL1-IL18R1-IL18RAP (P(combined) = 8.36 × 10(-18)), the major histocompatibility complex (MHC) region (P = 8.38 × 10(-20)), OR10A3-NLRP10 (P = 1.54 × 10(-22)), GLB1 (P = 2.77 × 10(-16)), CCDC80 (P = 1.56 × 10(-19)), CARD11 (P = 7.83 × 10(-9)), ZNF365 (P = 5.85 × 10(-20)) and CYP24A1-PFDN4 (P = 1.65 × 10(-8)). We also replicated the associations of the FLG, C11orf30, TMEM232-SLC25A46, TNFRSF6B-ZGPAT, OVOL1, ACTL9 and KIF3A-IL13 loci that were previously reported in GWAS of European and Chinese individuals and a meta-analysis of GWAS for atopic dermatitis. These findings advance the understanding of the genetic basis of atopic dermatitis.

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The stratum corneum (SC), the outermost layer of the epidermis, acts as a barrier against the external environment. It is hydrated by endogenous humectants to avoid desiccation. However, the molecular mechanisms of SC hydration remain unclear. We report that skin-specific retroviral-like aspartic protease (SASPase) deficiency in hairless mice resulted in dry skin and a thicker and less hydrated SC with an accumulation of aberrantly processed profilaggrin, a marked decrease of filaggrin, but no alteration in free amino acid composition, compared with control hairless mice. We demonstrated that recombinant SASPase directly cleaved a linker peptide of recombinant profilaggrin. Furthermore, missense mutations were detected in 5 of 196 atopic dermatitis (AD) patients and 2 of 28 normal individuals. Among these, the V243A mutation induced complete absence of protease activity in vitro, while the V187I mutation induced a marked decrease in its activity. These findings indicate that SASPase activity is indispensable for processing profilaggrin and maintaining the texture and hydration of the SC. This provides a novel approach for elucidating the complex pathophysiology of atopic dry skin.

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Bullous pemphigoid (BP) is a blistering skin disease in which autoantibodies develop to hemidesmosomal components of the epidermal basement membrane zone, including two major antigenic proteins of the 230-kD antigen (BPAG1 ) and the 180-kD antigen (BPAG2). The present study demonstrated the precise ultrastructural localization of the epitopes for autoantibodies against BPAG1 and BPAG2 in normal skin. Autoantibodies against either BPAG1 or BPAG2 were affinity-purified using nitrocellulose membrane, which was blotted with SDS-PAGEfractionated antigens from human epidermal extract as the immunoabsorbent. Postembedding, immunogold electron microscopy was performed after skin was processed by rapid freezing and freeze substitution fixation without chemical fixatives. Purified autoantibodies against BPAG1 bound only to the intracellular domain of the hemidesmosome, and 80% of the gold labeling was within 40-140 nm from the plasma membrane (mean distance 91 nm inside). In contrast, the autoantibodies against BPAG2 bound along the plasma membrane of the hemidesmosome, and 80% of the gold labeling was within 10 nm outside to 50 nm inside the cells (mean distance 12 nm inside). These results suggest that the autoantibodies against BPAG1 and BPAG2 react with the epitopes localizing in distinct regions of the hemidesmosome complex, and may play different roles in the blister formation in patients with

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