Exosome-Mediated Crosstalk between Keratinocytes and Macrophages in Cutaneous Wound Healing

Bidirectional cell–cell communication involving exosome-borne cargo such as miRNA has emerged as a critical mechanism for wound healing. Unlike other shedding vesicles, exosomes selectively package miRNA by SUMOylation of heterogeneous nuclear ribonucleoproteinA2B1 (hnRNPA2B1). In this work, we elucidate the significance of exosome in keratinocyte–macrophage crosstalk following injury. Keratinocyte-derived exosomes were genetically labeled with GFP-reporter (Exoκ-GFP) using tissue nanotransfection (TNT), and they were isolated from dorsal murine skin and wound-edge tissue by affinity selection using magnetic beads. Surface N-glycans of Exoκ-GFP were also characterized. Unlike skin exosome, wound-edge Exoκ-GFP demonstrated characteristic N-glycan ions with abundance of low-base-pair RNA and was selectively engulfed by wound macrophages (ωmϕ) in granulation tissue. In vitro addition of wound-edge Exoκ-GFP to proinflammatory ωmϕ resulted in conversion to a proresolution phenotype. To selectively inhibit miRNA packaging within Exoκ-GFPin vivo, pH-responsive keratinocyte-targeted siRNA-hnRNPA2B1 functionalized lipid nanoparticles (TLNPκ) were designed with 94.3% encapsulation efficiency. Application of TLNPκ/si-hnRNPA2B1 to the murine dorsal wound-edge significantly inhibited expression of hnRNPA2B1 by 80% in epidermis compared to the TLNPκ/si-control group. Although no significant difference in wound closure or re-epithelialization was observed, the TLNPκ/si-hnRNPA2B1 treated group showed a significant increase in ωmϕ displaying proinflammatory markers in the granulation tissue at day 10 post-wounding compared to the TLNPκ/si-control group. Furthermore, TLNPκ/si-hnRNPA2B1 treated mice showed impaired barrier function with diminished expression of epithelial junctional proteins, lending credence to the notion that unresolved inflammation results in leaky skin. This work provides insight wherein Exoκ-GFP is recognized as a major contributor that regulates macrophage trafficking and epithelial barrier properties postinjury

An Urban Composite Development Index based on China's Five Development Concepts

10.1108/CR-08-2019-0079Competitiveness Review302137-14

Investigation of High-Temperature Normal Infrared Spectral Emissivity of ZrO2 Thermal Barrier Coating Artefacts by the Modified Integrated Blackbody Method

Zirconium oxide (ZrO2) is widely used as the thermal barrier coating in turbines and engines. Accurate emissivity measurement of ZrO2 coating at high temperatures, especially above 1000 °C, plays a vital role in thermal modelling and radiation thermometry. However, it is an extremely challenging enterprise, and very few high temperature emissivity results with rigorously estimated uncertainties have been published to date. The key issue for accurately measuring the high temperature emissivity is maintaining a hot surface without reflection from the hot environment, and avoiding passive or active oxidation of material, which will modify the emissivity. In this paper, a novel modified integrated blackbody method is reported to measure the high temperature normal spectral emissivity of ZrO2 coating in the temperature range 1000 °C to 1200 °C and spectral range 8 μm to 14 μm. The results and the associated uncertainty of the measurement were estimated and a relative standard uncertainty better than 7% (k = 2) is achieved

Targeting TNFα Ameliorated Cationic PAMAM Dendrimer-Induced Hepatotoxicity via Regulating NLRP3 Inflammasomes Pathway

Hepatotoxicity of cationic poly amidoamine (PAMAM) dendrimers is one of the most urgent challenges to their medicinal application. Recent studies have indicated that proinflammatory cytokines were critical in nanomaterials-induced toxicity. However, little is known about the roles and underlying regulatory mechanisms of proinflammatory cytokines in cationic PAMAM dendrimer-induced hepatotoxicity. Thus, the aim of the current study was to explore the role of proinflammatory cytokine tumor necrosis factor alpha (TNFα) in cationic PAMAM dendrimer-induced liver injury and its underlying mechanism and develop novel strategies to reduce hepatotoxicity of cationic PAMAM dendrimers through regulating TNFα. In this study, we verified the significant overexpression of TNFα in cationic PAMAM dendrimer-induced hepatotoxicity in mice and found that targeting TNFα by etanercept could protect against cationic PAMAM dendrimer-induced liver injury. Interestingly, etanercept suppressed cationic PAMAM dendrimer-induced inflammasome signaling as demonstrated by reduced activation of NALP3, cleavage of Caspase-1, and maturation of interleukin (IL)-1β. Moreover, suppression of NLRP3 inflammasomes by belnacasan could also protect against cationic PAMAM dendrimer-induced hepatotoxicity and TNFα-induced acute hepatotoxicity. Notably, targeting either TNFα or inflammasomes reduced autophagy activation in hepatotoxicity triggered by cationic PAMAM dendrimers. In general, these findings revealed that targeting TNFα could ameliorate cationic PAMAM dendrimer-induced hepatotoxicity via regulating NLRP3 inflammasome pathway, underscoring that TNFα antagonism by etanercept could be used as an effective pharmacological approach to control hepatotoxicity of cationic PAMAM dendrimers and thus providing novel therapeutic strategies for managing liver toxicity of nanomaterials via regulating inflammatory mediators