Drug delivery systems responsive to physicochemical stimuli allow spatiotemporal control over drug activity to overcome limitations of systemic drug administration. Alongside, the non-invasive ...real-time tracking of drug release and uptake remains challenging as pharmacophore and reporter function are rarely unified within one molecule. Here, we present an ultrasound-responsive release system based on the mechanochemically induced 5-
exo-trig
cyclization upon scission of disulfides bearing cargo molecules attached
via
β-carbonate linker within the center of a water soluble polymer. In this bifunctional theranostic approach, we release one reporter molecule per drug molecule to quantitatively track drug release and distribution within the cell in real-time. We use
N
-butyl-4-hydroxy-1,8-naphthalimide and umbelliferone as fluorescent reporter molecules to accompany the release of camptothecin and gemcitabine as clinically employed anticancer agents. The generality of this approach paves the way for the theranostic release of a variety of probes and drugs by ultrasound.
A theranostic approach for the mechanochemically induced release of drugs is presented to track drug release and uptake in real-time.
Pharmaceutical drug therapy is often hindered by issues caused by poor drug selectivity, including unwanted side effects and drug resistance. Spatial and temporal control over drug activation in ...response to stimuli is a promising strategy to attenuate and circumvent these problems. Here we use ultrasound to activate drugs from inactive macromolecules or nano-assemblies through the controlled scission of mechanochemically labile covalent bonds and weak non-covalent bonds. We show that a polymer with a disulfide motif at the centre of the main chain releases an alkaloid-based anticancer drug from its β-carbonate linker by a force-induced intramolecular 5-exo-trig cyclization. Second, aminoglycoside antibiotics complexed by a multi-aptamer RNA structure are activated by the mechanochemical opening and scission of the nucleic acid backbone. Lastly, nanoparticle-polymer and nanoparticle-nanoparticle assemblies held together by hydrogen bonds between the peptide antibiotic vancomycin and its complementary peptide target are activated by force-induced scission of hydrogen bonds. This work demonstrates the potential of ultrasound to activate mechanoresponsive prodrug systems.
Learning semantic attributes for person re-identification and description-based person search has gained increasing interest due to attributes' great potential as a pose and view-invariant ...representation. However, existing attribute-centric approaches have thus far underperformed state-of-the-art conventional approaches. This is due to their nonscalable need for extensive domain (camera) specific annotation. In this paper we present a new semantic attribute learning approach for person re-identification and search. Our model is trained on existing fashion photography datasets - either weakly or strongly labelled. It can then be transferred and adapted to provide a powerful semantic description of surveillance person detections, without requiring any surveillance domain supervision. The resulting representation is useful for both unsupervised and supervised person re-identification, achieving state-of-the-art and near state-of-the-art performance respectively. Furthermore, as a semantic representation it allows description-based person search to be integrated within the same framework.
The challenge of eradicating cancer is that cancer cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown to exhibit appreciable ...anti-tumor activity that could be harnessed for cancer therapy in the future. Ferroptosis is an iron-dependent form of regulated cell death that is characterized by the oxidization of polyunsaturated fatty acids (PUFAs) and accumulation of lipid peroxides. Ferroptosis has been closely correlated with numerous biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism, as well as key regulators including GPX4, FSP1, NRF2, and p53. Although ferroptosis could be involved in killing various cancer cells, multiple aspects of this phenomenon remain unresolved. In this review, we summarize the biochemistry and biology of ferroptosis in diverse cancers and discuss the potential mechanisms of ferroptosis, which might pave the way for guiding cancer therapeutics.
We propose to model complex visual scenes using a non-parametric Bayesian model learned from weakly labelled images abundant on media sharing sites such as Flickr. Given weak image-level annotations ...of objects and attributes without locations or associations between them, our model aims to learn the appearance of object and attribute classes as well as their association on each object instance. Once learned, given an image, our model can be deployed to tackle a number of vision problems in a joint and coherent manner, including recognising objects in the scene (automatic object annotation), describing objects using their attributes (attribute prediction and association), and localising and delineating the objects (object detection and semantic segmentation). This is achieved by developing a novel Weakly Supervised Markov Random Field Stacked Indian Buffet Process (WS-MRF-SIBP) that models objects and attributes as latent factors and explicitly captures their correlations within and across superpixels. Extensive experiments on benchmark datasets demonstrate that our weakly supervised model significantly outperforms weakly supervised alternatives and is often comparable with existing strongly supervised models on a variety of tasks including semantic segmentation, automatic image annotation and retrieval based on object-attribute associations.
Conventional point cloud simplification algorithms have problems including nonuniform simplification, a deficient reflection of point cloud characteristics, unreasonable weight distribution, and high ...computational complexity. A simplification algorithm, namely, the multi-index weighting simplification algorithm (MIWSA), is proposed in this paper. First, the point cloud is organized with a bounding box and kd-trees to find the neighborhood of each point, and the points are divided into small segments. Second, the feature index of each point is calculated to indicate the characteristics of the points. Third, the analytic hierarchy process (AHP) and criteria importance through intercriteria correlation (CRITIC) are applied to weight these indexes to determine whether each point is a feature point. Fourth, non-feature points are judged as saved or abandoned according to their spatial relationship with the feature points. To verify the effect of the MIWSA, 3D model scanning datasets are calculated and analyzed, as well as field area scanning datasets. The accuracy for the 3D model scanning datasets is assessed by the surface area and patch numbers of the encapsulated surfaces, and that for field area scanning datasets is evaluated by the DEM error statistics. Compared with existing algorithms, the overall accuracy of the MIWSA is 5% to 15% better. Additionally, the running time is shorter than most. The experimental results illustrate that the MIWSA can simplify point clouds more precisely and uniformly.
Multilayer hexagonal boron nitride (h-BN) is highly desirable as a dielectric substrate for the fabrication of two-dimensional (2D) electronic and optoelectronic devices. However, the controllable ...synthesis of multilayer h-BN in large areas is still limited in terms of crystallinity, thickness and stacking order. Here, we report a vapor-liquid-solid growth (VLSG) method to achieve uniform multilayer h-BN by using a molten Fe
B
alloy and N
as reactants. Liquid Fe
B
not only supplies boron but also continuously dissociates nitrogen atoms from the N
vapor to support direct h-BN growth on a sapphire substrate; therefore, the VLSG method delivers high-quality h-BN multilayers with a controllable thickness. Further investigation of the phase evolution of the Fe-B-N system reveals that isothermal segregation dominates the growth of the h-BN. The approach herein demonstrates the feasibility for large-area fabrication of van der Waals 2D materials and heterostructures.
We address the problem of localisation of objects as bounding boxes in images with weak labels. This weakly supervised object localisation problem has been tackled in the past using discriminative ...models where each object class is localised independently from other classes. We propose a novel framework based on Bayesian joint topic modelling. Our framework has three distinctive advantages over previous works: (1) All object classes and image backgrounds are modelled jointly together in a single generative model so that "explaining away" inference can resolve ambiguity and lead to better learning and localisation. (2) The Bayesian formulation of the model enables easy integration of prior knowledge about object appearance to compensate for limited supervision. (3) Our model can be learned with a mixture of weakly labelled and unlabelled data, allowing the large volume of unlabelled images on the Internet to be exploited for learning. Extensive experiments on the challenging VOC dataset demonstrate that our approach outperforms the state-of-the-art competitors.
Although stag beetles are a popular saprophytic insect, their gut microbiome has been poorly studied. Here, 16 S rRNA gene sequencing was employed to reveal the gut microbiota composition and ...functional variations between wild and domestic Dorcus hopei hopei (Dhh) larval individuals.
The results indicated a significant difference between the wild and domestic Dhh gut microbiota., the domestic Dhh individuals contained more gut microbial taxa (e.g. genera Ralstonia and Methyloversatilis) with xenobiotic degrading functions. The wild Dhh possesses gut microbiota compositions (e.g. Turicibacter and Tyzzerella ) more appropriate for energy metabolism and potential growth. This study furthermore assigned all Dhh individuals by size into groups for data analysis; which indicated limited disparities between the gut microbiota of different-sized D. hopei hopei larvae.
The outcome of this study illustrated that there exists a significant discrepancy in gut microbiota composition between wild and domestic Dhh larvae. In addition, the assemblage of gut microbiome in Dhh was primarily attributed to environmental influences instead of individual differences such as developmental potential or size. These findings will provide a valuable theoretical foundation for the protection of wild saprophytic insects and the potential utilization of the insect-associated intestinal microbiome in the future.
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