Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-19 [1][2][3][4] . Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators [5][6][7] . COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue 1,8,9 , in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.The pandemic human pathogenic SARS-CoV-2 coronavirus causes upper respiratory infections and subsequently COVID-19 lung disease that may get further complicated by septic multi-organ failure and comes with significant mortality 10,11 . Escalating immune activation with massive cytokine release seems to drive severe COVID-19 1-3 , possibly more than the virus infection itself. Mechanisms of viral
Biodegradable and biocompatible elastic materials for soft robotics, tissue engineering or stretchable electronics with good mechanical properties, tunability, modifiability, or healing properties drive technological advance, yet they are not durable under ambient conditions nor combine all attributes in a single platform. We have developed a versatile gelatin-based biogel, which is highly resilient with outstanding elastic characteristics yet degrades fully when disposed. It self-adheres, is rapidly healable and derived entirely from natural and food-safe constituents. We merge for the first time all favorable attributes in one material that is easy to reproduce, scalable and low-cost in production under ambient conditions. This biogel is a step towards durable, lifelike soft robotic and electronic systems that are sustainable and closely mimic their natural antetypes. Main: In 2025, an estimated 6 million tons of garbage will be generated per day 1 , with tech disposables being a rapidly growing contributor. End-of-lifetime appliances contain valuable materials that are laborious in recovery or toxic substances that are readily released into nature through landfilling or improper treatment 2. Biodegradable 3-6 and transient systems 7 are promising routes towards closing the loop on waste generation and create new opportunities for secure systems, but often at the cost of compromises in performance. Complex biological systems bridge this gap. They unite seemingly antagonistic properties-tough yet adaptive, durable and self-healing yet degradable-allowing them to perform a myriad of intricate tasks. Embodiments of technologies that intimately interface with humans naturally benefit from mimicking such soft, functional forms. A range of biomimetic systems 8 including soft machines 9 and electronic skins 10 achieve a high level of functionality by introducing self-healing 11,12 , intrinsic stretchability 13 , or the insightful merging of soft-to-hard materials 14. Waste flow issues and in vivo applications that avoid multiple surgeries are tackled with inextensible devices in the form of edible 3,15 and transient electronics 7,16. However, introducing stretchability to degradable devices remains challenging. Recent approaches focusing on stretchable biodegradable sensors 5 require expensive materials and are still wired to bulky measurement systems hindering implementation as wearable devices. Challenges here stem from the diverse material requirements,
Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a real-life clinical setting. Effectiveness and safety outcomes were collected at baseline and after 2, 6, 10, 24, 39, and 52 weeks by using clinical scores for disease activity, as well as serological markers. Ninety-four patients from five dermatological hospitals were included. After 24 weeks of treatment, the median Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI) showed a significant reduction compared to baseline (3.9 ± 0.7 vs. 1.4 ± 0.8 and 26.5 ± 12.5 vs. 6.4 ± 6.5). Interestingly, we observed rosacea-like folliculitis as an unexpected side effect in 6.4% of patients. Dupilumab proves to be an effective and well-tolerated treatment under real-life conditions. The occurrence of rosacea-like folliculitis warrants further mechanistic investigation.
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