The incidence of breast cancer is increasing rapidly around the world. Accurate classification of the breast cancer subtype from hematoxylin and eosin images is the key to improve the precision of treatment. However, the high consistency of disease subtypes and uneven distribution of cancer cells seriously affect the performance of multi-classification methods. Furthermore, it is difficult to apply existing classification methods to multiple datasets. In this article, we propose a collaborative transfer network (CTransNet) for multi-classification of breast cancer histopathological images. CTransNet consists of a transfer learning backbone branch, a residual collaborative branch, and a feature fusion module. The transfer learning branch adopts the pre-trained DenseNet structure to extract image features from ImageNet. The residual branch extracts target features from pathological images in a collaborative manner. The feature fusion strategy of optimizing these two branches is used to train and fine-tune CTransNet. Experiments show that CTransNet achieves 98.29% classification accuracy on the public BreaKHis breast cancer dataset, exceeding the performance of state-of-the-art methods. Visual analysis is carried out under the guidance of oncologists. Based on the training parameters of the BreaKHis dataset, CTransNet achieves superior performance on other two public breast cancer datasets (breast-cancer-grade-ICT and ICIAR2018_BACH_Challenge), indicating that CTransNet has good generalization performance.

Stroke is a cerebrovascular disease with high mortality and disability rates. The occurrence of the stroke typically produces lesions of different sizes, with the accurate segmentation and detection of small-size stroke lesions being closely related to the prognosis of patients. However, the large lesions are usually correctly identified, the small-size lesions are usually ignored. This article provides a hybrid contextual semantic network (HCSNet) that can accurately and simultaneously segment and detect small-size stroke lesions from magnetic resonance images. HCSNet inherits the advantages of the encoder-decoder architecture and applies a novel hybrid contextual semantic module that generates high-quality contextual semantic features from the spatial and channel contextual semantic features through the skip connection layer. Moreover, a mixing-loss function is proposed to optimize HCSNet for unbalanced small-size lesions. HCSNet is trained and evaluated on 2D magnetic resonance images produced from the Anatomical Tracings of Lesions After Stroke challenge (ATLAS R2.0). Extensive experiments demonstrate that HCSNet outperforms several other state-of-the-art methods in its ability to segment and detect small-size stroke lesions. Visualization and ablation experiments reveal that the hybrid semantic module improves the segmentation and detection performance of HCSNet.

Drug-induced liver injury (DILI) has always been the focus of clinicians and drug researchers. How to improve the performance of the DILI prediction model to accurately predict liver injury was an urgent problem for researchers in the field of medical research. In order to solve this scientific problem, this research collected a comprehensive and accurate dataset of DILI with high recognition and high quality based on clinically confirmed DILI compound datasets, including 1446 chemical compounds. Then, the residual neural network with 18-layer by using more 5-layer blocks (ResNet18) with deep neural network (ResNet18DNN) model was proposed to predict DILI, which was an improved model for DILI prediction through vectorization of compound structure image. In predicting DILI, the ResNet18DNN learned greatly and outperformed the existing state-of-the-art DILI predictors. The results of DILI prediction model based on ResNet18DNN showed that the AUC (area under the curve), accuracy, recall, precision, F1-score and specificity of the training set were 0.973, 0.992, 0.995, 0.994, 0.995 and 0.975; those of test set were, respectively, 0.958, 0.976, 0.935, 0.947, 0.926 and 0.913, which were better than the performance of previously published described DILI prediction models. This method adopted ResNet18 embedding method to vectorize molecular structure images and the evaluation indicators of Resnet18DNN were obtained after 10 000 iterations. This prediction approach will greatly improve the performance of the predictive model of DILI and provide an accurate and precise early warning method for DILI in drug development and clinical medication.

In the previous study, we developed the generalized drug-induced liver injury (DILI) prediction model-ResNet18DNN to predict DILI based on multi-source combined DILI dataset and achieved better performance than that of previously published described DILI prediction models. Recently, we were honored to receive the invitation from the editor to response the Letter to Editor by Liu Zhichao, et al. We were glad that our research has attracted the attention of Liu's team and they has put forward their opinions on our research. In this response to Letter to the Editor, we will respond to these comments.

Target identification of small molecules is an important and still changeling work in the area of drug discovery, especially for botanical drug development. Indistinct understanding of the relationships of ligand-protein interactions is one of the main obstacles for drug repurposing and identification of off-targets. In this study, we collected 9063 crystal structures of ligand-binding proteins released from January, 1995 to April, 2021 in PDB bank, and split the complexes into 5133 interaction pairs of ligand atoms and protein fragments (covalently linked three heavy atoms) with interatomic distance ≤5 Å. The interaction pairs were grouped into ligand atoms with the same SYBYL atom type surrounding each type of protein fragment, which were further clustered via Bayesian Gaussian Mixture Model (BGMM). Gaussian distributions with ligand atoms ≥20 were identified as significant interaction patterns. Reliability of the significant interaction patterns was validated by comparing the difference of number of significant interaction patterns between the docked poses with higher and lower similarity to the native crystal structures. Fifty-one candidate targets of brucine, strychnine and icajine involved in Semen Strychni (Mǎ Qián Zǐ) and eight candidate targets of astragaloside-IV, formononetin and calycosin-7-glucoside involved in Astragalus (Huáng Qí) were predicted by the significant interaction patterns, in combination with docking, which were consistent with the therapeutic effects of Semen Strychni and Astragalus for cancer and chronic pain. The new strategy in this study improves the accuracy of target identification for small molecules, which will facilitate discovery of botanical drugs.