Lung cancer is a disease that influences human health and has become a leading cause of cancer mortality worldwide. However, it is frequently diagnosed at the advanced stage. It is necessary by means of biology to identify specific lung tumor biomarkers with high sensitivity. Glycosylation is one of the most important post-translational modifications and is related to many different diseases. It is involved in numerous essential biological processes, such as cell proliferation, differentiation, migration, cell-cell integrity and recognition, and immune modulation. However, little was known about deregulation of glycosylation in lung cancer and contribution to tumor–microenvironment interactions. Among the numerous glycosylations, fucosylation is the most common modification of glycoproteins and glycosylated oligosaccharides. Increased levels of fucosylation have been detected in various pathological conditions, as well as in lung cancer. In this article, we reviewed the role of fucosylation in lung cancer. We highlighted some of the fucosylation alterations currently being pursued in sera or tissues of lung cancer patients. Moreover, we elaborated on the regulation mechanism of fucosylation in proliferative invasion and metastasis of lung tumor cells. In summary, alterations in fucosylation provide potential biomarkers and therapeutic targets in lung cancer.
Accurate assessment of renal histopathology is crucial for the clinical management of patients with lupus nephritis (LN). However, the current classification system has poor interpathologist agreement. This paper proposes a deep convolutional neural network (CNN)-based system that detects and classifies glomerular pathological findings in LN. A dataset of 349 renal biopsy whole-slide images (WSIs) (163 patients with LN, periodic acid-Schiff stain, 3906 glomeruli) annotated by three expert nephropathologists was used. The CNN models YOLOv4 and VGG16 were employed to localise the glomeruli and classify glomerular lesions (slight/severe impairments or sclerotic lesions). An additional 321 unannotated WSIs from 161 patients were used for performance evaluation at the per-patient kidney level. The proposed model achieved an accuracy of 0.951 and Cohen’s kappa of 0.932 (95% CI 0.915–0.949) for the entire test set for classifying the glomerular lesions. For multiclass detection at the glomerular level, the mean average precision of the CNN was 0.807, with ‘slight’ and ‘severe’ glomerular lesions being easily identified (F1: 0.924 and 0.952, respectively). At the per-patient kidney level, the model achieved a high agreement with nephropathologist (linear weighted kappa: 0.855, 95% CI: 0.795–0.916, p < 0.001; quadratic weighted kappa: 0.906, 95% CI: 0.873–0.938, p < 0.001). The results suggest that deep learning is a feasible assistive tool for the objective and automatic assessment of pathological LN lesions.
Safe and effective hemostatic materials are important for reducing mortality resulting from excessive hemorrhage. In this work, new biomaterials with hemostatic effects were created by fusing the gene coding for RADA-16, a self-assembling peptide with the sequence RADARADARADARADA, to the 3′-end of the open reading frame (ORF) encoding elastin-like polypeptides through gene recombination. The fusion proteins, termed 36R, 60R and 96R, were solubly over-expressed in Escherichia coli BL21 (DE3) based on genetic manipulation of the high-efficiency prokaryotic expression vector pET28a (+) and bacterial transformation. Western Blot analysis showed that the over-expressed proteins were the target fusion proteins. The target proteins 36R with 94.72% purity, 60R with 96.91% purity and 96R with 96.37% purity were prepared using an inverse phase transition cycle at 65 °C followed by His-tag affinity chromatography. The proliferation results of the mouse fibroblast cell line L929 and hippocampus neuron cell line HT22 indicated that the fusion proteins did not cause obvious cell toxicity. The lyophilized spongy film of the purified 36R, 60R and 96R could stop the hemorrhage of a 2 × 2 mm bleeding wound in the mouse liver after 27.21 ± 1.92 s, 18.65 ± 1.97 s and 15.85 ± 1.21 s, respectively. The hemostasis time was 21.23 ± 1.84 s for rat-tail collagen and 14.44 ± 1.33 s for RADA-16 lyophilized on gauze. The hemostatic time of three treated groups were all significantly superior to that of the negative control without any hemostasis treatment, which spontaneously stopped bleeding after 37.64 ± 1.34 s. Statistical analysis showed that the spongy film with purified 96R exhibited an exciting hemostatic effect that was superior to rat-tail collagen and close to that of RADA-16 lyophilized on gauze. These results revealed that the fusion proteins achieved by gene recombination technology could serve as a promising hemostatic material.
Skin wound repair remains a major challenge in clinical care, and various strategies have been employed to improve the repair process. Recently, it has been reported that macrophages are important for the regeneration of various tissues and organs. However, their influence on wound repair is unclear. Here, we aimed to explore whether macrophages would participate in the wound healing process and to explore new possibilities of treatment for skin defects. We firstly created a mouse full-thickness skin defect model to observe the distribution of macrophages in the regenerating tissue and then detected the influence of macrophages on skin defect repair in both macrophage-depletion and macrophage-mobilization models. We found that the number of macrophages increased significantly after skin defect and persisted during the process of wound repair. The regeneration process was significantly prolonged in macrophage-depleted animals. RT-qPCR and ELISA assays further demonstrated that the expression of growth factors was perturbed in the regenerating tissue. The activation of macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) injection could significantly improve wound healing, accompanied with an upregulation of the expression of various growth factors. In conclusion, the current study demonstrated that macrophages are critical for skin regeneration and that GM-CSF exhibited therapeutic potential for wound healing.