pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery

AbstractMost of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy. Based on physiological differences between the normal tissue and the tumor tissue, one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems. The copolymers with reversible protonation–deprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release. These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect, or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway. The pH-sensitive micelles have been proved the specific tumor cell targeting, enhanced cellular internalization, rapid drug release, and multidrug resistance reversal. The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting. The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells, which reverses multidrug resistance. The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy, and is a novel promising platform for tumor-targeting drug delivery

Faster OreFSDet : A Lightweight and Effective Few-shot Object Detector for Ore Images

For the ore particle size detection, obtaining a sizable amount of high-quality ore labeled data is time-consuming and expensive. General object detection methods often suffer from severe over-fitting with scarce labeled data. Despite their ability to eliminate over-fitting, existing few-shot object detectors encounter drawbacks such as slow detection speed and high memory requirements, making them difficult to implement in a real-world deployment scenario. To this end, we propose a lightweight and effective few-shot detector to achieve competitive performance with general object detection with only a few samples for ore images. First, the proposed support feature mining block characterizes the importance of location information in support features. Next, the relationship guidance block makes full use of support features to guide the generation of accurate candidate proposals. Finally, the dual-scale semantic aggregation module retrieves detailed features at different resolutions to contribute with the prediction process. Experimental results show that our method consistently exceeds the few-shot detectors with an excellent performance gap on all metrics. Moreover, our method achieves the smallest model size of 19MB as well as being competitive at 50 FPS detection speed compared with general object detectors. The source code is available at https://github.com/MVME-HBUT/Faster-OreFSDet.Comment: 18 pages, 11 figure

Knowledge Graph Alignment Network with Gated Multi-hop Neighborhood Aggregation

Graph neural networks (GNNs) have emerged as a powerful paradigm for embedding-based entity alignment due to their capability of identifying isomorphic subgraphs. However, in real knowledge graphs (KGs), the counterpart entities usually have non-isomorphic neighborhood structures, which easily causes GNNs to yield different representations for them. To tackle this problem, we propose a new KG alignment network, namely AliNet, aiming at mitigating the non-isomorphism of neighborhood structures in an end-to-end manner. As the direct neighbors of counterpart entities are usually dissimilar due to the schema heterogeneity, AliNet introduces distant neighbors to expand the overlap between their neighborhood structures. It employs an attention mechanism to highlight helpful distant neighbors and reduce noises. Then, it controls the aggregation of both direct and distant neighborhood information using a gating mechanism. We further propose a relation loss to refine entity representations. We perform thorough experiments with detailed ablation studies and analyses on five entity alignment datasets, demonstrating the effectiveness of AliNet.Comment: Accepted by the 34th AAAI Conference on Artificial Intelligence (AAAI 2020

SOLAR: A Highly Optimized Data Loading Framework for Distributed Training of CNN-based Scientific Surrogates

CNN-based surrogates have become prevalent in scientific applications to replace conventional time-consuming physical approaches. Although these surrogates can yield satisfactory results with significantly lower computation costs over small training datasets, our benchmarking results show that data-loading overhead becomes the major performance bottleneck when training surrogates with large datasets. In practice, surrogates are usually trained with high-resolution scientific data, which can easily reach the terabyte scale. Several state-of-the-art data loaders are proposed to improve the loading throughput in general CNN training; however, they are sub-optimal when applied to the surrogate training. In this work, we propose SOLAR, a surrogate data loader, that can ultimately increase loading throughput during the training. It leverages our three key observations during the benchmarking and contains three novel designs. Specifically, SOLAR first generates a pre-determined shuffled index list and accordingly optimizes the global access order and the buffer eviction scheme to maximize the data reuse and the buffer hit rate. It then proposes a tradeoff between lightweight computational imbalance and heavyweight loading workload imbalance to speed up the overall training. It finally optimizes its data access pattern with HDF5 to achieve a better parallel I/O throughput. Our evaluation with three scientific surrogates and 32 GPUs illustrates that SOLAR can achieve up to 24.4X speedup over PyTorch Data Loader and 3.52X speedup over state-of-the-art data loaders.Comment: 14 pages, 15 figures, 5 tables, submitted to VLDB '2

Integrating optical imaging techniques for a novel approach to evaluate Siberian wild rye seed maturity

Advances in optical imaging technology using rapid and non-destructive methods have led to improvements in the efficiency of seed quality detection. Accurately timing the harvest is crucial for maximizing the yield of higher-quality Siberian wild rye seeds by minimizing excessive shattering during harvesting. This research applied integrated optical imaging techniques and machine learning algorithms to develop different models for classifying Siberian wild rye seeds based on different maturity stages and grain positions. The multi-source fusion of morphological, multispectral, and autofluorescence data provided more comprehensive information but also increases the performance requirements of the equipment. Therefore, we employed three filtering algorithms, namely minimal joint mutual information maximization (JMIM), information gain, and Gini impurity, and set up two control methods (feature union and no-filtering) to assess the impact of retaining only 20% of the features on the model performance. Both JMIM and information gain revealed autofluorescence and morphological features (CIELab A, CIELab B, hue and saturation), with these two filtering algorithms showing shorter run times. Furthermore, a strong correlation was observed between shoot length and morphological and autofluorescence spectral features. Machine learning models based on linear discriminant analysis (LDA), random forests (RF) and support vector machines (SVM) showed high performance (>0.78 accuracies) in classifying seeds at different maturity stages. Furthermore, it was found that there was considerable variation in the different grain positions at the maturity stage, and the K-means approach was used to improve the model performance by 5.8%-9.24%. In conclusion, our study demonstrated that feature filtering algorithms combined with machine learning algorithms offer high performance and low cost in identifying seed maturity stages and that the application of k-means techniques for inconsistent maturity improves classification accuracy. Therefore, this technique could be employed classification of seed maturity and superior physiological quality for Siberian wild rye seeds

Effect of Functional Oligosaccharides and Ordinary Dietary Fiber on Intestinal Microbiota Diversity

Functional oligosaccharides, known as prebiotics, and ordinary dietary fiber have important roles in modulating the structure of intestinal microbiota. To investigate their effects on the intestinal microecosystem, three kinds of diets containing different prebiotics were used to feed mice for 3 weeks, as follows: GI (galacto-oligosaccharides and inulin), PF (polydextrose and insoluble dietary fiber from bran), and a GI/PF mixture (GI and PF, 1:1), 16S rRNA gene sequencing and metabolic analysis of mice feces were then conducted. Compared to the control group, the different prebiotics diets had varying effects on the structure and diversity of intestinal microbiota. GI and PF supplementation led to significant changes in intestinal microbiota, including an increase of Bacteroides and a decrease of Alloprevotella in the GI-fed, but those changes were opposite in PF fed group. Intriguing, in the GI/PF mixture-fed group, intestinal microbiota had the similar structure as the control groups, and flora diversity was upregulated. Fecal metabolic profiling showed that the diversity of intestinal microbiota was helpful in maintaining the stability of fecal metabolites. Our results showed that a single type of oligosaccharides or dietary fiber caused the reduction of bacteria species, and selectively promoted the growth of Bacteroides or Alloprevotella bacteria, resulting in an increase in diamine oxidase (DAO) and/or trimethylamine N-oxide (TMAO) values which was detrimental to health. However, the flora diversity was improved and the DAO values was significantly decreased when the addition of nutritionally balanced GI/PF mixture. Thus, we suggested that maintaining microbiota diversity and the abundance of dominant bacteria in the intestine is extremely important for the health, and that the addition of a combination of oligosaccharides and dietary fiber helps maintain the health of the intestinal microecosystem

Panicle Nitrogen Strategies for Nitrogen-Efficient Rice Varieties at a Moderate Nitrogen Application Rate in the Lower Reaches of the Yangtze River, China

Nitrogen (N) management is of great importance in rice production, but most previous studies have focused on high N rates and there is a lack of research on management plans under a moderate N rate. This study aimed to explore the agronomic and physiological traits of N-efficient rice varieties (NEVs) and to optimize the management strategy at an N rate below the inflection point of the parabolic curve between N rate and grain yield. Two NEVs and two N-inefficient rice varieties (NIVs) were planted, and three treatments were designed according to the panicle N application method. A larger amount of N applied at panicle initiation (PI) led to higher rice yield and N-use efficiency (NUE). This was mainly due to increases in the total number of spikelets per unit area, root oxidation activity, leaf area duration, and leaf photosynthesis rate as well as to the increased carbon (C) and N utilization rates. Compared with NIVs, NEVs exhibited improved root and shoot functions and higher C and N transport characteristics at the moderate N rate. We suggest that increasing the application of N at PI and that planting of NEVs are important ways to increase rice yield and NUE when adopting moderate N rates