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Creators/Authors contains: "Chen, Zeyu"

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  1. Abstract The skin is our outer permeability and immune defense barrier against myriad external assaults. Aryl hydrocarbon receptor (AhR) senses environmental factors and regulates barrier robustness and immune homeostasis. AhR agonists have been approved by the FDA for psoriasis treatment and are in clinical trials for the treatment of atopic dermatitis (AD), but the underlying mechanism of action remains poorly defined. Here, we report thatOVOL1/Ovol1is a conserved and direct transcriptional target of AhR in epidermal keratinocytes. We show that OVOL1/Ovol1 influences AhR-mediated regulation of keratinocyte gene expression and thatOVOL1/Ovol1ablation in keratinocytes impairs the barrier-promoting function of AhR, exacerbating AD-like inflammation. Mechanistically, we have identified Ovol1’s direct downstream targets genome-wide and provided in vivo evidence supporting the role ofId1as a functional target in barrier maintenance, disease suppression, and neutrophil accumulation. Furthermore, our findings reveal that an IL-1/dermal γδT cell axis exacerbates type 2 and 3 immune responses downstream of barrier perturbation inOvol1-deficient AD skin. Finally, we present data suggesting the clinical relevance of OVOL1 and ID1 functions in human AD skin. Our study highlights a keratinocyte-intrinsic AhR-Ovol1-Id1 regulatory axis that promotes both epidermal and immune homeostasis in the context of skin inflammation, identifying new therapeutic targets. 
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  2. Abstract Skin epidermis constitutes the outer permeability barrier that protects the body from dehydration, heat loss, and myriad external assaults. Mechanisms that maintain barrier integrity in constantly challenged adult skin and how epidermal dysregulation shapes the local immune microenvironment and whole‐body metabolism remain poorly understood. Here, we demonstrate that inducible and simultaneous ablation of transcription factor‐encodingOvol1andOvol2in adult epidermis results in barrier dysregulation through impacting epithelial‐mesenchymal plasticity and inflammatory gene expression. We find that aberrant skin immune activation then ensues, featuring Langerhans cell mobilization and T cell responses, and leading to elevated levels of secreted inflammatory factors in circulation. Finally, we identify failure to gain body weight and accumulate body fat as long‐term consequences of epidermal‐specificOvol1/2loss and show that these global metabolic changes along with the skin barrier/immune defects are partially rescued by immunosuppressant dexamethasone. Collectively, our study reveals key regulators of adult barrier maintenance and suggests a causal connection between epidermal dysregulation and whole‐body metabolism that is in part mediated through aberrant immune activation. 
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  3. null (Ed.)
  4. Abstract An additive manufacturing-enabled bi-continuous piezocomposite architecture is presented to achieve mechanical flexibility and piezoelectricity simultaneously in piezoelectric materials. This architecture comprises an active ferroelectric ceramic phase and a passive flexible polymer phase, which are separated by a tailorable phase interface. Triply periodic minimal surfaces were used to define the phase interface, due to their excellent elastic properties and load transfer efficiency. A suspension-enclosing projection-stereolithography process was used to additively manufacture this material. Postprocesses including polymer infiltration, electroding, and poling are introduced. Piezoelectric properties of the piezocomposites are numerically and experimentally studied. The results highlight the role of tailorable triply periodic phase interfaces in promoting mechanical flexibility and piezoelectricity of bi-continuous piezocomposites. 
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  5. null (Ed.)
  6. Abstract Nature has developed high‐performance materials and structures over millions of years of evolution and provides valuable sources of inspiration for the design of next‐generation structural materials, given the variety of excellent mechanical, hydrodynamic, optical, and electrical properties. Biomimicry, by learning from nature's concepts and design principles, is driving a paradigm shift in modern materials science and technology. However, the complicated structural architectures in nature far exceed the capability of traditional design and fabrication technologies, which hinders the progress of biomimetic study and its usage in engineering systems. Additive manufacturing (three‐dimensional (3D) printing) has created new opportunities for manipulating and mimicking the intrinsically multiscale, multimaterial, and multifunctional structures in nature. Here, an overview of recent developments in 3D printing of biomimetic reinforced mechanics, shape changing, and hydrodynamic structures, as well as optical and electrical devices is provided. The inspirations are from various creatures such as nacre, lobster claw, pine cone, flowers, octopus, butterfly wing, fly eye, etc., and various 3D‐printing technologies are discussed. Future opportunities for the development of biomimetic 3D‐printing technology to fabricate next‐generation functional materials and structures in mechanical, electrical, optical, and biomedical engineering are also outlined. 
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