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Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC. [ABSTRACT FROM AUTHOR]

High-quality ontologies are critical to ontology-based applications, such as natural language understanding and information extraction, but logical conflicts naturally occur in the lifecycle of ontology development. To deal with such conflicts, conflict detection and ontology repair become two critical tasks, and we focus on repairing ontologies. Most existing approaches for ontology repair rely on the syntax of axioms or logical consequences but ignore the semantics of axioms. In this paper, we propose an embedding-based approach by considering sentence embeddings of axioms, which translates axioms into semantic vectors and provides facilities to compute semantic similarities among axioms. A threshold-based algorithm and a signature-based algorithm are designed to repair ontologies with the help of detected conflicts and axiom embeddings. In the experiments, our proposed algorithms are compared with existing ones over 20 real-life incoherent ontologies. The threshold-based algorithm with different distance metrics is further evaluated with 10 distinct thresholds and 3 pre-trained models. The experimental results show that the embedding-based algorithms could achieve promising performances. [ABSTRACT FROM AUTHOR]

Experiencing nature can induce the perception of happiness because of mental stress alleviation and well-being restoration. The largeness of green space may not always mean the frequency of experiencing greenery. It is arguing about the probability of positive sentiments in response to an experience of interacting with green nature. In this study, 38 green spaces were investigated in Nanchang City, China, where the green space area was evaluated by the largeness of the landscape metrics of the Normalized Vegetation Index (NDVI), and Green View Index (GVI) data were further obtained using Open Street Maps (OSM). The semantic segmentation method was used by machine learning to analyze a total of 1549 panoramic photos taken in field surveys to assess the Panoramic Green View Index (PGVI) proportion. The photos of 2400 people's facial expressions were obtained from social networks at their check-in visits in green spaces and rated for happy and sad scores using FireFACE software. Split-plot analysis of variance suggested that different categories of NDVI largeness had a significant positive effect on posted positive sentiments. Multivariate linear regression indicated that PGVI was estimated to have a significant contribution to facial expression. Increasing the amount of PGVI promoted happy and PRI scores, while at the same time, neutral sentiments decreased with increasing PGVI. Overall, increasing the PGVI in green spaces, especially in parks with smaller green spaces, can be effective in promoting positive emotions in the visitor experience. [ABSTRACT FROM AUTHOR]

A facile and efficient approach for design and synthesis of organic fluorescent nanogels has been developed by using a pre-synthesized polymeric precursor. This strategy is achieved by two key steps: (i) precise synthesis of core–shell star-shaped block copolymers with crosslinkable AIEgen-precursor (AIEgen: aggregation induced emission luminogen) as pending groups on the inner blocks; (ii) gelation of the inner blocks by coupling the AIEgen-precursor moieties to generate AIE-active spacers, and thus, fluorescent nanogel. By using this strategy, a series of star-shaped block copolymers with benzophenone groups pending on the inner blocks were synthesized by grafting from a hexafunctional initiator through atom transfer radical copolymerization (ATRP) of 4-benzoylphenyl methacrylate (BPMA) or 2-(4-benzoylphenoxy)ethyl methacrylate (BPOEMA) with methyl methacrylate (MMA) and tert-butyldimethylsilyl-protected 2-hydroxyethyl methacrylate (ProHEMA) followed by a sequential ATRP to grow PMMA or PProHEMA. The pendent benzophenone groups were coupled by McMurry reaction to generate tetraphenylethylene (TPE) groups which served as AIE-active spacers, affording a fluorescent nanogel. The nanogel showed strong emission not only at aggregated state but also in dilute solution due to the strongly restricted inter- and intramolecular movement of TPE moiety in the crosslinked polymeric network. The nanogel has been used as a fluorescent macromolecular additive to fabricate fluorescent film. [ABSTRACT FROM AUTHOR]