Breast cancer is a significant health issue for women, and human epidermal growth factor receptor-2 (HER2) plays a crucial role as a vital prognostic and predictive factor. The HER2 status is essential for formulating effective treatment plans for breast cancer. However, the assessment of HER2 status using immunohistochemistry (IHC) is time-consuming and costly. Existing computational methods for evaluating HER2 status have limitations and lack sufficient accuracy. Therefore, there is an urgent need for an improved computational method to better assess HER2 status, which holds significant importance in saving lives and alleviating the burden on pathologists.This paper analyzes the characteristics of histological images of breast cancer and proposes a neural network model named HAHNet that combines multi-scale features with attention mechanisms for HER2 status classification. HAHNet directly classifies the HER2 status from hematoxylin and eosin (H&E) stained histological images, reducing additional costs. It achieves superior performance compared to other computational methods.According to our experimental results, the proposed HAHNet achieved high performance in classifying the HER2 status of breast cancer using only H&E stained samples. It can be applied in case classification, benefiting the work of pathologists and potentially helping more breast cancer patients.
Abstract Background Osteoarthritis (OA) is one of the most common degenerative diseases. Accumulating evidence suggests that ferroptosis may be important in the progression of OA. Angelica Sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses antioxidative, anti-inflammatory and anti-apoptotic properties. However, it is unclear whether ASP can slow down the progression of osteoarthritis by suppressing ferroptosis. Methods Collection of postoperative joint cartilage from patients who underwent total knee arthroplasty (TKA), detection of ferroptosis-related markers including glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1) expression, as well as glutathione (GSH) and malondialdehyde (MDA) levels, and investigation of the correlation between ferroptosis and osteoarthritis. Chondrocytes were isolated and cultured, stimulated separately with IL-1β or erastin, rescued by ASP and ferroptosis inhibitors, and changes in cell viability and ferroptosis were detected. A destabilization of the medial meniscus surgical model (DMM) model was established in mice, and ASP was administered orally at different dosages to evaluate its therapeutic effect and level of ferroptosis. Results First, the expression of GPX4, FTH1 and reduced GSH was lower while the MDA level was up-regulated in cartilage of the OA group as compared to the control group. Moreover, chondrocyte ferroptosis induced by Erastin or IL-1β was rescued by the application of ASP or ferroptosis inhibitors in vitro . Further, the anti-ferroptotic effect of ASP was related to enhanced nuclear transfer of Nrf2 and decreased activation of NF-κB as indicated by down-regulated expression of p-p65. Next, the in vivo experiments showed that ASP alleviated the cartilage damage of mice joints induced by DMM. Conclusions In summary, ASP can attenuate chondrocyte ferroptosis through the Nrf2/NF-κB pathway in the progression of OA, suggesting that ASP may a potential inhibitor of ferroptosis for the treatment of OA.
Reducing the toxicity of silver-based antibacterial agents used in gels and improving their biocompatibility are of great significance in the development of wound dressings. Thus, a highly crosslinked organic–inorganic hybrid porous polyphosphazene nanospheres (PRV-HMSs) were prepared via precipitation polymerization. The structures and properties were investigated. The results indicated that PRV-HMSs have uniform particle size about 500 nm, excellent thermal stability, high silver loading (26.5 wt.%) and remarkable sustained-release properties after loading AgNO 3 (up to 2 weeks). The antibacterial effects were investigated with zone of inhibition testing, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), Live/Dead bacterial staining assay and bacterial growth curve assays. The silver-loaded nanospheres have excellent bactericidal effects for E. coli or S. aureus and an average bactericidal rate of 94.02% and 94.67% in the 120 hour long-acting antibacterial test. The cytotoxicity and laser confocal immunofluorescence staining experiments indicate that the simple combination of nanospheres and agar not only give low cytotoxicity, but also significantly promote the activation of macrophages, which showing potential application in the wound dressings based on hydrogel.
Grounded Multimodal Named Entity Recognition (GMNER) is a nascent multimodal task that aims to identify named entities, entity types and their corresponding visual regions. GMNER task exhibits two challenging properties: 1) The weak correlation between image-text pairs in social media results in a significant portion of named entities being ungroundable. 2) There exists a distinction between coarse-grained referring expressions commonly used in similar tasks (e.g., phrase localization, referring expression comprehension) and fine-grained named entities. In this paper, we propose RiVEG, a unified framework that reformulates GMNER into a joint MNER-VE-VG task by leveraging large language models (LLMs) as a connecting bridge. This reformulation brings two benefits: 1) It maintains the optimal MNER performance and eliminates the need for employing object detection methods to pre-extract regional features, thereby naturally addressing two major limitations of existing GMNER methods. 2) The introduction of entity expansion expression and Visual Entailment (VE) Module unifies Visual Grounding (VG) and Entity Grounding (EG). It enables RiVEG to effortlessly inherit the Visual Entailment and Visual Grounding capabilities of any current or prospective multimodal pretraining models. Extensive experiments demonstrate that RiVEG outperforms state-of-the-art methods on the existing GMNER dataset and achieves absolute leads of 10.65%, 6.21%, and 8.83% in all three subtasks.
Siamese fighting fish Betta splendens are notorious for their aggressiveness and accordingly have been widely used to study aggression. However, the lack of a reference genome has so far limited the understanding of the genetic basis of aggression in this species. Here we present the first reference genome assembly of the Siamese fighting fish.<br>We first sequenced and de novo assembled a 465.24 Mb genome for the B. splendens variety Giant, with a weighted average (N50) scaffold size of 949.03 Kb and an N50 contig size of 19.01 Kb, covering 99.93% of the estimated genome size. To obtain a chromosome-level genome assembly, we constructed one Hi-C library and sequenced 75.24 Gb reads using the BGISEQ-500 platform. We anchored approximately 93% of the scaffold sequences into 21 chromosomes and evaluated the quality of our assembly using the high contact frequency heatmap and BUSCO. We also performed comparative chromosome analyses between Oryzias latipes and B. splendens, revealing a chromosome conservation evolution in B. splendens. We predicted a total of 23,981 genes assisted by RNA-seq data generated from brain, liver, muscle and heart tissues of Giant, and annotated 15% repetitive sequences in the genome. Additionally, we resequenced other five B. splendens varieties and detected ~3.4M single-nucleotide variations (SNVs) and 27,305 indels.<br>We provide the first chromosome-level genome for the Siamese fighting fish. The genome will lay a valuable foundation for future research on aggression in B. splendens.
Abstract Exosomes derived from cancer are regarded as significant mediators of cancer-host crosstalk. Hypoxia, on the other hand, is one of the essential characteristics of solid tumors. This research set out to discover how circulating exosomes from hypoxic esophageal squamous cell carcinoma (ESCC) contribute to the formation of metastatic niches and distant metastasis. First, we noticed that human umbilical vein endothelial cells (HUVECs) had their tight connections disrupted and the expression of proteins involved in angiogenesis boosted by ESCC hypoxic exosomes. Hypoxia significantly induced Circ-ZNF609 expression in exosomes from ESCC, which was then internalized by HUVECs, as determined by circular RNA screening. High Circ-ZNF609 expression in HUVECs facilitated angiogenesis and vascular permeability, thereby promoting pre-metastatic niche formation, and enhancing distant metastasis in vitro and in vivo. Exosomal Circ-ZNF609 activated vascular endothelial growth factor A (VEGFA) mechanistically by sponging miR-150-5p. Exosomal Circ-ZNF609 also interacted with HuR and inhibited HuR binding to ZO-1, Claudin-1, and Occludin mRNAs, thereby reducing their translation. Collectively, our findings identified an essential function for exosomal Circ-ZNF609 from ESCC cells, suggesting the potential therapeutic value of exosomes for ESCC patients.
BGISEQ-500 is a new desktop sequencer developed by BGI. Using DNA nanoball and combinational probe anchor synthesis developed from Complete Genomics™ sequencing technologies, it generates short reads at a large scale.
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