RESUMEN
Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2-hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two-step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re-epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual-enhanced cell and tissue penetration and multistep interventions.
Asunto(s)
Diabetes Mellitus Experimental , Sistemas de Liberación de Medicamentos , Vesículas Extracelulares , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Vesículas Extracelulares/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Humanos , Modelos Animales de Enfermedad , Ratones , Quitosano/química , Robótica/métodos , RatasRESUMEN
Fluorescent RNAs (FRs) provide an attractive approach to visualizing RNAs in live cells. Although the color palette of FRs has been greatly expanded recently, a green FR with high cellular brightness and photostability is still highly desired. Here we develop a fluorogenic RNA aptamer, termed Okra, that can bind and activate the fluorophore ligand ACE to emit bright green fluorescence. Okra has an order of magnitude enhanced cellular brightness than currently available green FRs, allowing the robust imaging of messenger RNA in both live bacterial and mammalian cells. We further demonstrate the usefulness of Okra for time-resolved measurements of ACTB mRNA trafficking to stress granules, as well as live-cell dual-color superresolution imaging of RNA in combination with Pepper620, revealing nonuniform and distinct distributions of different RNAs throughout the granules. The favorable properties of Okra make it a versatile tool for the study of RNA dynamics and subcellular localization.
RESUMEN
Existing cross-domain classification and detection methods usually apply a consistency constraint between the target sample and its self-augmentation for unsupervised learning without considering the essential source knowledge. In this paper, we propose a Source-guided Target Feature Reconstruction (STFR) module for cross-domain visual tasks, which applies source visual words to reconstruct the target features. Since the reconstructed target features contain the source knowledge, they can be treated as a bridge to connect the source and target domains. Therefore, using them for consistency learning can enhance the target representation and reduce the domain bias. Technically, source visual words are selected and updated according to the source feature distribution, and applied to reconstruct the given target feature via a weighted combination strategy. After that, consistency constraints are built between the reconstructed and original target features for domain alignment. Furthermore, STFR is connected with the optimal transportation algorithm theoretically, which explains the rationality of the proposed module. Extensive experiments on nine benchmarks and two cross-domain visual tasks prove the effectiveness of the proposed STFR module, e.g., 1) cross-domain image classification: obtaining average accuracy of 91.0%, 73.9%, and 87.4% on Office-31, Office-Home, and VisDA-2017, respectively; 2) cross-domain object detection: obtaining mAP of 44.50% on Cityscapes â Foggy Cityscapes, AP on car of 78.10% on Cityscapes â KITTI, MR -2 of 8.63%, 12.27%, 22.10%, and 40.58% on COCOPersons â Caltech, CityPersons â Caltech, COCOPersons â CityPersons, and Caltech â CityPersons, respectively.