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Abstract: In this paper, we study the following Linear Complementarity problem: f : R n →R n , find x ≥0, such that f(x)≥0, x T f (x)=0.We use Poineare-Bohn''s homotopy invariance theorem of degree to derive an alternative theorem, and give a new exceptional families. Based on this result, for the nonlinear complementarity problems with a quasi- P * -mapping or a P(τ, α, β) -mapping or a semi-monotone mapping, a sufficiently condition is established to assure the existence and boundedness of solution curve [Copyright &y& Elsevier]

Abstract: In this paper, a combined interior point homotopy method is used to solve constrained nonconvex programming problems. Some results for the homotopy pathway are obtained. It is known that a K–K–T point can be obtained from this homotopy method, and it proves that, when the homotopy map is a regular map, the K–K–T point must be a local minimum point on choosing a proper homotopy equation. [Copyright &y& Elsevier]

• MiRNA sequencing for exosomes. • Some selective exosomal miRNAs from retinal pigment epithelial cells expressed by oxidative stress. • Potential functions and targets of the differentially expressed exosomal miRNAs. The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1β, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy. [ABSTRACT FROM AUTHOR]

Aims Proliferative diabetic retinopathy (PDR), characterized by angiogenesis, can cause serve vision loss and even blindness. Recent studies have suggested a pivotal role of vasohibin-2 (VASH2) in the promotion of angiogenesis in tumor tissues. Here we further investigated the role of VASH2 in the proliferation and migration of retinal endothelial cells. Main methods The expression of VASH2 in vascular endothelial cells of epiretinal fibrovascular membranes (FVMs) from PDR patients were detected by immunofluorescence. VASH2 gene interfering lentiviral vectors ( VASH2 -shRNA) and miR-200b/c were constructed for the evaluation of the VASH2 effect on high glucose induced human retinal microvascular endothelial cell line (HRMECs). Cell proliferation, cell cycle and cell migration were carried out subsequently. The relationship between VASH2 and miR-200b/c was determined by luciferase reporter gene assays. Key findings A positive expression of VASH2 was identified in vascular endothelial cells of FVMs from PDR patients. In HRMECs, cells transfected with shRNA or miR-200b/c mimics showed a significantly reduced VASH2 expression compared with negative control group by real time-polymerase chain reaction and western-blot analysis. Inhibition of VASH2 was demonstrated to suppress cell proliferation and migration from Day 2 to Day 4. The luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200b/c in HRMECs. Significance The present study suggests a protective effect of miR-200b/c on high glucose induced HRMECs dysfunction by inhibiting VASH2. It could be a potential therapeutic strategy to inhibit angiogenesis for the treatment of retinal vascular disease. [ABSTRACT FROM AUTHOR]

Recent studies were mainly focus on the cytidine deaminase family genes, which contained a lot of members that varied on the function of catalytic deamination in RNA or DNA and were involved in the process of growth maintenance, host immunity, retroviral infection, tumorigenesis, and drug resistance with a feature of C-U deamination. In this study, we identified a new member of cytidine deaminase family, NYD-SP15. Previous work showed that the deduced structure of the protein contained two dCMP_cyt_deam domains, which were involved in zinc ion binding. NYD-SP15 was expressed variably in a wide range of tissues, indicating its worthy biological function and creative significances. Sequence analysis, RT-PCR, western blot, flow cytometry, direct-site mutation and GST pull-down assay were performed to analyze the construction and function of NYD-SP15. The results in our studies showed that NYD-SP15 was closely related to deoxycytidylate deaminase and cytidine deaminase, with authentic cytidine deaminase activity in vivo and vitro as well as homo dimerization effects. NYD-SP15 contained nuclear localization sequence (NLS) and nuclear export-signal (NES) and could dynamically shuttle between the nucleus and cytoplasm. Furthermore, NYD-SP15 gene over-expression reduced the cells growth and blocked G1 to S phase, which implied a potential inhibition effect on cell growth. [ABSTRACT FROM AUTHOR]

Objective: To assess the role of the age-related maculopathy susceptibility 2 (ARMS2) A69S polymorphism as a risk factor for polypoidal choroidal vasculopathy (PCV) in Asian populations. Methods: We performed a meta-analysis of the association of the A69S variant with PCV in Asian populations using data available from 14 case-control studies involving 6552 subjects. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. Sensitivity analysis also was performed. Main Outcome Measures: Understanding the relationship between the A69S variant and PCV is essential to provide new insights into pathophysiology and potential targets for intervention of PCV. Results: The pooled OR in random-effects models for genotype TG+TT versus wild homozygous genotype GG is 2.39 (95% CI, 1.98–2.89), the OR of heterozygous genotype TG versus GG is 1.66 (95% CI, 1.37–2.00), the OR of homozygous genotype TT versus GG is 4.74 (95% CI, 3.94–5.70), and the OR of allele T versus G is 2.14 (95% CI, 1.79–2.56). A sensitivity analysis indicated the robustness of our findings. Conclusions: Our analysis provides evidence that the A69S variant is associated with an increased risk of PCV in Asian populations. The variant of A69S could be a promising genetic biomarker of PCV. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]