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Collectively, SA3K protects against oxidative stress by targeting the ROS generation/degradation system and modulating the KEAP1-NRF2 signaling pathway.

Purpose: To evaluate the anti-neovascularization effects and investigate the possible mechanisms of SERPINA3K, a member of serine proteinase inhibitor family, using a specific rat model of suture-induced corneal neovascularization. Methods: A rat corneal suture model was set up and SERPINA3K was topically administered three times daily for 7 days. The clinical indications were evaluated on day 2, 5 and 7, including area of neovascularization and inflammation index. The eyeballs were collected after day 7 and the following examinations were performed: histological investigation, immunostaining, western blot and quantitative real-time polymerase chain reaction (PCR) assay. Wnt3a, a Wnt pathway ligand, was added to cultured Human Umbilical Vein Endothelial Cells (HUVEC), followed by detecting cell migration and western blot. Meanwhile, an in vitro VEGF165-stimulated HUVEC model was applied and the following measurements were conducted: cell proliferation, cell migration and tube formation. Results: SERPINA3K significantly suppressed corneal neovascularization and inhibited corneal inflammation. SERPINA3K downregulated the levels of β-catenin, non-pi-β-catenin and transcription factor 4 (TCF4), but upregulated the level of pi-β-catenin of the corneas induced by suture. SERPINA3K also decreased the gene expression and protein level of VEGF. Meanwhile, induction of Wnt3a increased the cell migration, activated the Wnt signaling and upregulated VEGF in cultured HUVEC, which were antagonized by SERPINA3K. In addition, SERPINA3K significantly inhibited VEGF165-induced cell proliferation and migration of HUVEC, SERPINA3K also specifically suppressed the VEGF165-induced tube formation of HUVEC. Conclusions: SERPINA3K has therapeutic potential for corneal neovascularization. The underlying mechanism may be through inhibiting Wnt signaling pathway and VEGF.

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We recently demonstrated that SERPINA3K, a serine proteinase inhibitor, has antioxidant activity in the cornea. Here we investigated the antioxidant effects of SERPINA3K on the pterygial, which is partially caused by oxidative stress in pathogenesis. The head part of primary pterygial tissue was dissected and then cultured in keratinocyte serum-free defined medium (KSFM). The cultured pterygial epithelial cells (PECs) were treated with SERPINA3K. The cell proliferation and migration of PECs were measured and analyzed. Western blot and quantitative real-time polymerase chain reaction (PCR) assay were performed. It showed that SERPINA3K significantly suppressed the cell proliferation of PECs in a concentration-dependent manner, compared with cultured human conjunctival epithelial cells. SERPINA3K also inhibited the cell migration of PECs. Towards its underlying mechanism, SERPINA3K had antioxidant activities on the PECs by significantly inhibiting NADPH oxidase 4 (NOX4), which is an important enzyme of ROS generation, and by elevating the levels of key antioxidant factors of ROS: such as NAD(P)H dehydrogenase (quinone 1) (NQO1), NF-E2–related factor-2 (NRF2) and superoxide dismutases (SOD2). Meanwhile, SERPINA3K down-regulated the key effectors of Wnt signaling pathway: β-catenin, nonphospho-β-catenin, and low-density lipoprotein receptor-related protein 6 (LRP6). We provided novel evidence that SERPINA3K had inhibitory effects on pterygium and SERPINA3K played antioxidant role via regulating the ROS system and antioxidants.

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This work extends the matrix pencil method (MPM)-based synthesis technique to the case of nonuniformly spaced linear arrays with wideband frequency-invariant (FI) patterns. A new sampling strategy is proposed to obtain multiple pattern data of different frequencies having the same poles that correspond to the FI element positions. The obtained multiple pattern sequences have the same shape for the FI pattern requirement, but with different lengths. The generalized MPM (GMPM) and its forward-backward version (GFBMPM) are developed to estimate the best common element positions for different frequencies, which can significantly reduce the number of elements required for the specified wideband pattern shape. The element excitations are solved by the regularized least-square (LS) method at each frequency. Then an efficient method by utilizing the FFT is presented to obtain real-coefficient finite-impulse-response (FIR) filters for implementing the frequency-varying excitations. A set of numerical examples for the FI synthesis of pencil-beams, shaped patterns, scannable patterns and Taylor patterns with low sidelobe levels, are presented to validate the effectiveness and advantages of the proposed methods. The element saving is about 11.2% − 49.4% for usual cases.Index Terms-Nonuniformly spaced array, wideband array, frequency-invariant pattern, generalized matrix pencil method.