Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR Are Based on Highly Similar Proteome and Degradome Alterations.

Keratinocyte-specific deletion of ADAM17 in mice impairs terminal differentiation of keratinocytes leading to severe epidermal barrier defects. Mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of epidermal growth factor receptor (EGFR), which highlights the role of ADAM17 as a "ligand sheddase" of EGFR ligands. In this study, we aim for the first proteomic/degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its consequences for epidermal barrier formation. Proteomic profiling of the epidermal proteome of mice deficient for either ADAM17 or EGFR in keratinocytes at postnatal days 3 and 10 revealed highly similar protein alterations for ADAM17 and EGFR deficiency. These include massive proteome alterations of structural and regulatory components important for barrier formation such as transglutaminases, involucrin, filaggrin, and filaggrin-2. Cleavage site analysis using terminal amine isotopic labeling of substrates revealed increased proteolytic processing of S100 fused-type proteins including filaggrin-2. Alterations in proteolytic processing are supported by altered abundance of numerous proteases upon keratinocyte-specific Adam17 or Egfr deletion, among them kallikreins, cathepsins, and their inhibitors. This study highlights the essential role of proteolytic processing for maintenance of a functional epidermal barrier. Furthermore, it suggests that most defects in formation of the postnatal epidermal barrier upon keratinocyte-specific ADAM17 deletion are mediated via EGFR.

A study on smart home use intention of elderly consumers based on technology acceptance models.

PURPOSE: Smart home devices have great potential to improve the quality of life and independence of older people, positively impacting their health, safety, and comfort. However, Chinese research in this field is still in its early stages. Therefore, more comprehensive and in-depth studies are needed to comprehend the various aspects influencing the acceptance and use of smart homes by older users. PATIENTS AND METHODS: This study adopted the Technology Acceptance Model (TAM) and included perceived usefulness, perceived ease of use, usage intention, intergenerational technology support, perceived value, and perceived risk as extension variables to delve deeper into the behavioral intentions of older users in smart home services. The study used a convenience sampling method to randomly distribute 236 questionnaires among older adults over the age of 60 in the school's community and neighboring urban communities who have experience in smart home use and who can complete human-computer interactions either independently or with the help of others, mainly focusing on the four sections: user characteristics, family situation, experience of use, and usage intention. The study used structural equation modeling (SEM) and factor analysis to analyze the completion of questionnaires. Finally, we conducted a validation analysis of the rationality and scientificity of the model and derived the six dimensions of the model of the influencing factors on the use of smart home products by the elderly and the weight sizes of their corresponding 13 influencing factors. RESULTS: The results show that perceived usefulness and perceived ease of use have a positive effect on users' intention to use smart homes. Perceived ease of use has a positive effect on the perceived usefulness of smart homes. In addition, intergenerational technology support, perceived value, and perceived risk impact users' perceived usefulness and perceived ease of use of the smart home. CONCLUSION: This research aims to describe the factors influencing older users' willingness to use smart homes. The findings are not only significant for the elderly in China but also of broad value to other regions and countries facing similar demographic challenges. The development of smart homes not only involves the elderly but is also closely related to all segments of society. The government should increase policy support and guide more social forces to participate in the development of the smart home industry. Service providers and designers should fully understand the demand situation and user experience of target users to develop easy-to-use smart home solutions. At the same time, smart homes, as intelligent products for the elderly, need to focus not only on the basic needs of the elderly such as material life and home safety, but also on the spiritual needs of elderly users. Children or caregivers should always pay attention to the psychological state of the elderly and actively guide them to use smart homes to help them realize their self-worth. We look forward to more research focusing on this area in the future and further exploring the specific issues and solutions involved.

The impact of different age-friendly smart home interface styles on the interaction behavior of elderly users.

Smart homes create a beneficial environment for the lives of elderly people and enhance the quality of their home lives. This study aims to explore the design of age-friendly interfaces that can meet the emotional needs of self-care elderly people from the perspective of functional realization of the operating interface. Sixteen elderly users aged fifty-five and above were selected as subjects with healthy eyes and no excessive drooping eyelids to obscure them. Four representative age-friendly applications with different interface designs were selected from the Android application market as the stimulus material for the experiment, and a total of fifteen pages were browsed independently. During the experiment, the ErgoLAB human-computer environment synchronization cloud platform was used to monitor and record the subjects' multidimensional physiological indicators of eye movements, skin electricity, and heart rate variability when using different styles of mobile application interfaces. Combined with the post-experimental PAD emotion scale data, the preferences of emotional interface design elements of the self-care elderly were analyzed to guide the subsequent design practice. The results show that: on the layout characteristics of the home page, a simple and intuitive multi-column layout or card layout combined with a bottom navigation bar type main navigation is used; on the choice of the main color, a single color with low saturation is used as the main color, with high saturation color accents to play a role in highlighting key information; on the information density of the home page, a moderate proportion of graphics and text is adopted, with low information density; on the arrangement of the page content, they try to give priority to information content with high user relevance.

ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways.

The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression. Restored TG1 expression of EGF-stimulated differentiated Adam17-/- keratinocytes was strongly repressed by inhibitors for PLCγ1 or protein kinase C (PKC) pathways, while treatment with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate restored TG activity in the epidermis of keratinocyte-specific Adam17-/- (AD17ΔKC) mice. Further investigations emphasized the expression of PKCη, a mediator of TGM1 transcription, to be sensitive to EGFR activation. In agreement, topical skin application of cholesterol sulfate, an activator of PKCη, significantly improved TG activity in epidermis of AD17ΔKC mice. Our results suggest ADAM17/EGFR-driven PLCγ1 and PKC pathways as important promoters of TG1 expression during terminal keratinocyte differentiation. These findings may help to identify new therapeutic targets for inflammatory skin diseases related to epidermal barrier defects.