A novel magnetic hydrogel is formed via the field-directed assembly of magnetic nanomaterials during the gelation process. The novel magnetic hydrogel exhibits direction-dependent thermogenesis in an alternating magnetic field. The specific absorption rate value in the direction along the assemblies can be 2.1-fold as much as that in the direction normal to the assemblies while the heating rate is 6-8-fold. Due to the anisotropic thermogenesis, the novel magnetic hydrogel also shows a direction-dependent release of drugs that has a 3.4-fold difference between the two directions.

SignificanceIn proliferative diabetic retinopathy (PDR), the most vision-threatening sequela of diabetic eye disease, retinal ischemia leads to increased expression of angiogenic factors that promote neovascularization. Although therapies targeting the potent angiogenic mediator vascular endothelial growth factor have been remarkably successful for the treatment of diabetic macular edema, this approach has not proven sufficient to prevent the development of retinal neovascularization, implicating additional angiogenic factor(s) in PDR pathogenesis. We demonstrate here that angiopoietin-like 4 is a potent angiogenic mediator with markedly increased expression in the eyes of PDR patients. Our studies identify a novel therapeutic target for the treatment of ocular neovascular disease and may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis.

Background: The Covid-19 pandemic restricts children and adolescents from doing normal daily activities such as playing outdoors and going to school. The incidence and prevalence of myopia have increased during the COVID-19 pandemic. The aim of this study was to investigate and evaluate the impact of the home confinement during the COVID-19 pandemic on the progression of myopia among children and adolescents in Chongqing, China.Methods: The survey was conducted by using stratified samplings. Samples were randomly selected from the 2019 National Student Physique and Health Survey database, and their visual function and refractive data were compared with those in 2020. Vision-related behavior questionnaire including digital screen exposure was applied to investigate the correlation between eye parameter and eye health-related behavior.Results: A total of 1,733 and 1,728 students were enrolled in 2020 and 2019, respectively. The percentage of myopia students was 55.02% in 2020, which was higher than that in 2019 (44.62%). The mean uncorrected visual acuity (UCVA, LogMAR, 0.35 ± 0.42) in 2020 was higher than that in 2019 (0.27 ± 0.36, P < 0.001). The mean spherical equivalent (SE) refraction (−1.94 ± 2.13 D) in 2020 was lower than that in 2019 (−1.64 ± 5.49 D, P < 0.001). For students who used digital devices for online courses, the mean SE in the television group (−1.10 ± 1.49 D) was better than that in the computer group (−2.03 ± 2.37 D, P = 0.0017) and in the cell phone group (−2.02 ± 2.09 D, P = 0.0028). The average duration of online classes (r = −0.27, P < 0.0001), the number of online classes per day (r = −0.33, P < 0.0001), as well as digital screen exposure time (r = −0.20, P < 0.0001) were negatively correlated with SE, and the average time of outdoor activity (r = 0.20, P < 0.0001) was positively correlated with SE.Conclusions: Increased digital screen exposure contributes to myopic progression in children and adolescents of Chongqing during the COVID-19 pandemic. Suitable digital devices should be provided for online classes and outdoor activity should be advocated to prevent myopic pandemic.

PurposeExpression of the hypoxia-inducible factor (HIF)-1-regulated gene product, vascular endothelial growth factor (VEGF), correlates with tumor vascularity in patients with uveal melanoma (UM). While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution to the angiogenic phenotype in UM has not previously been interrogated. Here we evaluate the contribution of HIF-1, VEGF, and a second HIF-1-regulated gene product, angiopoietin-like 4 (ANGPTL4), to angiogenesis in UM.Experimental DesignUM cells were examined for expression of HIF-1α, VEGF, and ANGPTL4. Their contribution to the angiogenic potential of UM cells was assessed using the endothelial cell tubule formation and directed in vivo angiogenesis assays. These results were corroborated in tissue from UM animal models and in tissue from patients with UM.ResultsInhibition of VEGF partially reduced tubule formation promoted by conditioned medium from UM cells. Inhibition of ANGPTL4, which was highly expressed in hypoxic UM cells, a UM orthotopic transplant model, a UM tumor array, and vitreous samples from UM patients, inhibited the angiogenic potential of UM cells in vitro and in vivo; this effect was additive to VEGF inhibition.ConclusionsTargeting both ANGPTL4 and VEGF may be required for the effective inhibition of angiogenesis in UM.

Glutathione peroxidase-1 (GPx1) is a pivotal intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. This study aims to identify a microRNA (miRNA) that targets GPx1 to maintain redox homeostasis. Dual luciferase assays combined with mutational analysis and immunoblotting were used to validate the bioinformatically predicted miRNAs. We sought to select miRNAs that were responsive to oxidative stress induced by hydrogen peroxide (H2O2) in the H9c2 rat cardiomyocyte cell line. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-181a in H2O2-treated H9c2 cells was markedly upregulated. The downregulation of miR-181a significantly inhibited H2O2-induced cellular apoptosis, ROS production, the increase in malondialdehyde (MDA) levels, the disruption of mitochondrial structure, and the activation of key signaling proteins in the mitochondrial apoptotic pathway. Our results suggest that miR-181a plays an important role in regulating the mitochondrial apoptotic pathway in cardiomyocytes challenged with oxidative stress. MiR-181a may represent a potential therapeutic target for the treatment of oxidative stress-associated cardiovascular diseases.

To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, P(combined) = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P(combined) = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P(combined) = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.

During activity-guided fractionations to screen for antineoplastic agents, further studies by means of preparative HPLC led to the isolation of four known furostanol saponins: protoneodioscin, protodioscin, protoneogracillin, protogracillin, along with their corresponding artifacts: methyl protoneodioscin, methyl protodioscin, methyl protoneogracillin, and methyl protogracillin, from the rhizomes of Dioscorea collettii var. hypoglauca. Among them, protoneodioscin, protodioscin, and protoneogracillin are first reported from the title plant. The structures of the compounds were established on the basis of chemical evidence and spectral analysis (1H-NMR, 13C-IMMR, 1H-1H COSY, HMQC, HMBC, and FAB-MS). These eight compounds all caused morphological abnormality of Pyricularia oryzae mycelia. They also showed cytotoxic activities against the cancer cell line of K562 in vitro as antineoplastic agents.

By activity-guided fractionation, three known steroidal saponins, prosapogenin A of dioscin, dioscin and gracillin, were isolated from the total saponin fraction of Dioscorea coiletti var. hypoglauca as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic activity against the cancer cell line K562 in vitro. The structures of the compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H-NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis.