The Annexin A2/S100A10 System in Health and Disease: Emerging Paradigms

Since its discovery as a src kinase substrate more than three decades ago, appreciation for the physiologic functions of annexin A2 and its associated proteins has increased dramatically. With its binding partner S100A10 (p11), A2 forms a cell surface complex that regulates generation of the primary fibrinolytic protease, plasmin, and is dynamically regulated in settings of hemostasis and thrombosis. In addition, the complex is transcriptionally upregulated in hypoxia and promotes pathologic neoangiogenesis in the tissues such as the retina. Dysregulation of both A2 and p11 has been reported in examples of rodent and human cancer. Intracellularly, A2 plays a critical role in endosomal repair in postarthroplastic osteolysis, and intracellular p11 regulates serotonin receptor activity in psychiatric mood disorders. In human studies, the A2 system contributes to the coagulopathy of acute promyelocytic leukemia, and is a target of high-titer autoantibodies in patients with antiphospholipid syndrome, cerebral thrombosis, and possibly preeclampsia. Polymorphisms in the human ANXA2 gene have been associated with stroke and avascular osteonecrosis of bone, two severe complications of sickle cell disease. Together, these new findings suggest that manipulation of the annexin A2/S100A10 system may offer promising new avenues for treatment of a spectrum of human disorders

Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1, Targeting FGFR2IIIc for Skin Wound Healing

Background/Aims: How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small peptide targeting fibroblast growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound healing. Methods: A phage-displayed peptide library was used for biopanning FGFR2IIIc-targeting small peptides. The selected small peptides binding to FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay. Their biological function was detected by a cell proliferation assay. Among them, an optimized small peptide named H1 was selected for further study. The affinity of the H1 peptide and FGFR2IIIc was determined by an isothermal titration calorimetry device. The ability of theH1 peptide to promote skin wound repair was investigated using an endothelial cell tube formation assay and wound healing scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat skin full-thickness wound model and chorioallantoic membrane (CAM) assays in vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR, and western blot assays were performed. Computer molecular simulations were also conducted to analyze the binding model. Results: We identified a novel FGFR2IIIc-targeting small peptide, called H1, with 7 amino acid residues using phage display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the proliferation and motility of fibroblasts and vascular endothelial cells in vitro. In addition, the H1 peptide enhanced angiogenesis in the chick chorioallantoic membrane and accelerated wound healing in a rat full-thickness wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2 pathways and simultaneously increased the secretion of vascular endothelial growth factor. Computer analysis demonstrated that the model of H1 peptide binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc. Conclusion: The H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound healing agent. As a substitute for bFGF, it could be developed into a novel therapeutic candidate for skin wound repair in the future

Molecular definition of group 1 innate lymphoid cells in the mouse uterus

Determining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.This work was funded by a Wellcome Trust Investigator Award 200841/Z/16/Z, the Centre for Trophoblast Research (CTR), and the Cambridge NIHR BRC Cell Phenotyping Hub to FC, the Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) - Special Project 5x1000 no. 9962, AIRC IG 2017 Id.19920 and AIRC 2014 Id. 15283 to LM, and Ministero della Salute RF-2013, GR-2013-02356568 to PV. IF was funded by a CTR PhD fellowship

An Improved 3D Registration Method of Mobile Augmented Reality for Urban Built Environment

3D registration plays a pivotal role in augmented reality (AR) system. The existing methods are not suitable to be applied directly in the mobile AR system for the built environment, with the reasons of poor real-time performance and robustness. This paper proposes an improved 3D registration method of mobile AR for built environment, which is based on SURFREAK and KLT. This method increases the building efficiency of algorithm descriptors and maintains the robustness of the algorithms. To implement and evaluate the registration method, a smart phone-based mobile AR system for built environment is developed. The experimental result shows that the improved method is endowed with higher real-time performance and robustness, and the mobile AR 3D registration can realize a favorable performance and efficiency in the complex built environment. The mobile AR system could be used in building recognition and information augmentation for built environment and further to facilitate location-based games, urban heritage tourism, urban planning, and smart city

UMHexagonS search algorithm for fast motion estimation

Conference Name:2011 3rd International Conference on Computer Research and Development, ICCRD 2011. Conference Address: Shanghai, China. Time:March 11, 2011 - March 15, 2011.In video coding, motion estimation is the most time consuming part due to its high computational complexity. Based on the high temporal and spatial correlation of motion vector (MV), a new fast motion estimation algorithm of UMHexagonS (UMH) has been proposed to reduce computational complexity by using relatively few search points without degrading image quality, in which the modified patterns with new uneven cross, multi-hexagon-grid and hexagon are applied to. The proposed algorithm alleviates the computational burden and maintains the quality of video. Compared with the original UMH algorithm, the proposed algorithm has a better performance, and it reduces the number of search points by 32% at least and preserves similar average peak signal-to-noise ratio (PSNR) value at the same time. ? 2011 IEEE

Synthetic Minority Oversampling Enhanced FEM for Tool Wear Condition Monitoring

Recent advances in artificial intelligence (AI) technology have led to increasing interest in the development of AI-based tool wear condition monitoring methods, heavily relying on large training samples. However, the high cost of tool wear experiment and the uncertainty of tool wear change in the machining process lead to the problems of sample missing and insufficiency in the model training stage, which seriously affects the identification accuracy of many AI models. In this paper, a novel identification method based on finite-element modeling (FEM) and the synthetic minority oversampling technique (SMOTE) is proposed to overcome the problem of sample missing and sample insufficiency. Firstly, a few tool wear monitoring experiments are carried out to obtain experimental samples with low cost. Then, a FEM model based on the Johnson–Cook constitutive model was established and verified according to the experimental samples. Based on the verified FEM model, the simulated missing sample in the experiments can be supplemented to compose a complete training set. Finally, the SMOTE is employed to expand the sample size to construct a perfect training set to train the SVM classification model. End milling tool wear monitoring experiments demonstrate that the proposed FEM-SMOTE method can obtain 98.7% identification accuracy, which is 30% higher than that based on experimental samples. The proposed method provides an effective approach for tool wear condition monitoring with low experimental cost

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of pre-eclampsia. Until now, the mechanisms underlying eclampsia were poorly understood. Brain edema is considered a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9), the glial water channel proteins mainly expressed in the nervous system, play an important role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms involved in brain edema. Using our previous animal models, we found several neuronal deaths in the hippocampal CA1 and CA3 regions after pre-eclampsia and that eclampsia induced more neuronal deaths in both areas by Nissl staining. In the current study, RT-PCR and Western blotting data showed significant upregulation of AQP4 and AQP9 mRNA and protein levels after eclamptic seizures in comparison to pre-eclampsia and at the same time AQP4 and AQP9 immunoreactivity also increased after eclampsia. These findings showed that eclamptic seizures induced cell death and that upregulation of AQP4 and AQP9 may play an important role in this pathophysiological process

Application of Three-Dimensional Printing Technology to the Manufacture of Petroleum Drill Bits

Drill bits are the main rock-breaking tools in the petroleum and gas industry. Their performance directly affects the quality, efficiency, and cost of drilling. Drill bit manufacturing mainly employs traditional mold forming processes such as milling molding and press molding, which have low production efficiency and long processing cycles and are not conducive to rapid responses to field requirements. Inadequate production accuracy makes it difficult to produce drill bits with complex structures. Three-dimensional (3D) printing technology has fast molding speeds and high molding accuracy. In this paper, 3D printing was applied for the first time to the manufacture of molds for carcass polycrystalline diamond compact (PDC) drill bits and PDC–cone hybrid drill bits. In comparison with forging and milling molding, 3D printing improved production efficiency. The manufactured molds had higher machining accuracy. The ability of 3D printing to make molds with complex surfaces enables the development of drill bits with complex structures. A field experiment was conducted on a PDC drill bit produced by 3D printing, which had a higher rate of penetration and was more efficient in breaking rocks than bits manufactured by traditional processes. The ROP of the drill bit increased by 20.1–25.8%, and the drilling depth increased by 7.7–29.5%. It is therefore feasible to apply 3D printing to the manufacture of petroleum drill bits