Stensgaardlohse3573
Therefore, upon the irradiation of 808 nm NIR light, the combinatorial photodynamic, photothermal and chemotherapy is achieved, accordingly leading to a highly efficient antitumor outcome in vitro and in vivo. This strategy provides an ideal approach to constructing multimodal cancer therapy system. STATEMENT OF SIGNIFICANCE • Dual-responsive nanohybrids for combinatorial therapy of breast cancer. • The nanohybrids exhibit both HAase and GSH stimuli-responsive behavior. • The nanohybrids exhibit light-activated PDT/PTT/chemotherapy. • The nanohybrids show good biosafety for potential clinical application.Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) show great therapeutic potential for osteoarthritis (OA). However, their low bioavailability through intraarticular injection inhibits the process of clinical application. In the present study, an injectable Diels-Alder crosslinked hyaluronic acid/PEG (DAHP) hydrogel was developed as an intraarticular delivery platform for MSC-sEVs. Our results showed that the DAHP hydrogel could be prepared easily and that its gelation properties were suitable for intraarticular administration. In vitro studies demonstrated that the DAHP hydrogel could achieve sustained release of MSC-sEVs mainly by degradation control and preserve the therapeutic functions of sEVs. click here An in vivo experiment revealed that the DAHP hydrogel could enhance the efficacy of MSC-sEVs for OA improvement. This study provides a suitable delivery platform for MSC-sEVs-based OA therapy. STATEMENT OF SIGNIFICANCE Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) have shown a high potential as a cell-free therapeutic factor for treating osteoarthritis (OA). The sustained release of these MSC-sEVs in the joint space is essential for their clinical application. Herein, an injectable Diels-Alder crosslinked hyaluronic acid/PEG (DAHP) hydrogel was developed for intraarticular release of MSC-sEVs. The properties of the DAHP hydrogel, namely gelation features, cytocompatibility, sustained release, and functional maintenance of MSC-sEVs, make it suitable for intraarticular injection and delivery of sEVs. The efficacy of MSC-sEVs was enhanced by the intraarticularly injected DAHP hydrogel. Our present study provides a promising sustained delivery platform for MSC-sEVs for treating OA.Silk fiber is renowned for its superb mechanical properties, such as over 7 times the toughness of Kevlar 49 Fibre. As the spider silk is tougher than any man-made fiber, there is a lot to be learned from spider silk. Recently, it has been reported that a large portion of the properties of silk is from naturally formed nano-fishnet structures of silk, but neither its formation mechanism nor its formation condition has been explained. Here, we show how the formation and disappearance of nano-fishnet of silk is determined by humidity, and how the humidity-dependency of nano-fishnet formation can be overcome by changing density of Arginine through sequence mutation. We demonstrate that the nano-fishnet-structured silk exhibits higher strength and toughness than its counterparts. This information on controllable nano-fishnet formation of silk is expected to pave the way for development of protein and synthetic fiber design. STATEMENT OF SIGNIFICANCE Silk fibers are a very interesting material in that it exhibits superb mechanical properties such as 7 times the toughness of Kevlar 49 Fibre, despite being only composed of proteins. Therefore, it is important that we understand the principle of its high mechanical properties so that it may be applied in designing synthetic fibers. Recently, it has been reported that a large portion of its mechanical property comes from its nano-fishnet structures, but no detailed explanation on the condition or mechanism of formation. Through molecular dynamic simulations, we simulated the nano-fishnet formation of silk and analyzed the condition and mechanism behind it, and showed how the formation of nano-fishnet structures could be controlled by changing the density of Arginine residues. Our study provides information on fiber enhancement mechanism that could be applied to synthetic and protein fiber design.Nepenthes pitcher plants grow in nutrient-poor soils and produce large pitfall traps to obtain additional nutrients from animal prey. Previous research has shown that the digestive secretion in N. rafflesiana is a sticky viscoelastic fluid that retains insects much more effectively than water, even after significant dilution. Although the retention of prey is known to depend on the fluid's physical properties, the details of how the fluid interacts with insect cuticle and how its sticky nature affects struggling insects are unclear. In this study, we investigated the mechanisms behind the efficient prey retention in N. rafflesiana pitcher fluid. By measuring the attractive forces on insect body parts moved in and out of test fluids, we show that it costs insects more energy to free themselves from pitcher fluid than from water. Moreover, both the maximum force and the energy required for retraction increased after the first contact with the pitcher fluid. We found that insects sink more easily into pitcher fld, the fluid strongly resists dewetting, making it harder for insects to extract themselves and covering their cuticle with residues that facilitate re-wetting. Such striking inhibition of dewetting may represent a previously unrecognised mechanism of prey retention by Nepenthes. Pitcher fluid fulfils a well-defined biological function and may serve as a model for studying the mechanics of complex fluids.Treating infection causing microorganisms is one of the major challenges in wound healing. These may gain resistance due to the overuse of conventional antibiotics. A promising technique is antimicrobial photodynamic therapy (aPDT) used to selectively cause damage to infectious pathogenic cells via generation of reactive oxygen species (ROS). We report on biocompatable nanomaterials that can serve as potential photosensitizers for aPDT. GO/Zn(Cu)O nanocomposite was synthesized by co-precipitation method. Graphene Oxide (GO) is known for its high surface to volume ratio, excellent surface functionality and enhanced antimicrobial property. ZnO nanoparticle induces the generation of reactive oxygen species (ROS) under light irradiation and it leads to recombination of electron-hole pair. Nanocomposites of GO and Cu doped ZnO increases visible light absorption and enhances the photocatalytic property. It generates more ROS and increases the bacterial inhibition. GO/Zn(Cu)O nanocomposite was tested against Staphylococcus aureus (S.