DME-DeepLabV3+: a lightweight model for diabetic macular edema extraction based on DeepLabV3+ architecture.

Introduction: Diabetic macular edema (DME) is a major cause of vision impairment in the patients with diabetes. Optical Coherence Tomography (OCT) is an important ophthalmic imaging method, which can enable early detection of DME. However, it is difficult to achieve high-efficiency and high-precision extraction of DME in OCT images because the sources of OCT images are diverse and the quality of OCT images is not stable. Thus, it is still required to design a model to improve the accuracy of DME extraction in OCT images. Methods: A lightweight model (DME-DeepLabV3+) was proposed for DME extraction using a DeepLabV3+ architecture. In this model, MobileNetV2 model was used as the backbone for extracting low-level features of DME. The improved ASPP with sawtooth wave-like dilation rate was used for extracting high-level features of DME. Then, the decoder was used to fuse and refine low-level and high-level features of DME. Finally, 1711 OCT images were collected from the Kermany dataset and the Affiliated Eye Hospital. 1369, 171, and 171 OCT images were randomly selected for training, validation, and testing, respectively. Conclusion: In ablation experiment, the proposed DME-DeepLabV3+ model was compared against DeepLabV3+ model with different setting to evaluate the effects of MobileNetV2 and improved ASPP on DME extraction. DME-DeepLabV3+ had better extraction performance, especially in small-scale macular edema regions. The extraction results of DME-DeepLabV3+ were close to ground truth. In comparative experiment, the proposed DME-DeepLabV3+ model was compared against other models, including FCN, UNet, PSPNet, ICNet, and DANet, to evaluate DME extraction performance. DME-DeepLabV3+ model had better DME extraction performance than other models as shown by greater pixel accuracy (PA), mean pixel accuracy (MPA), precision (Pre), recall (Re), F1-score (F1), and mean Intersection over Union (MIoU), which were 98.71%, 95.23%, 91.19%, 91.12%, 91.15%, and 91.18%, respectively. Discussion: DME-DeepLabV3+ model is suitable for DME extraction in OCT images and can assist the ophthalmologists in the management of ocular diseases.

Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization.

Long non-coding RNAs (lncRNAs) have been widely implicated in human diseases. Our aim was to explore the regulatory role of changes in the expression levels of PNKY and its linked signaling networks in mediating stress-induced choroidal neovascularization. PNKY expression levels were reduced in mice by laser and exposure of endothelial cell to hypoxic stress. PNKY silencing exacerbated the formation of CNV in a laser-induced CNV model and an ex vivo model, while overexpression inhibited CNV development. Silencing or overexpression of PNKY altered the viability, proliferation, migration, and tube-forming capacity of endothelial cells in vitro. Mechanistically, through the lncRNA-RNA binding protein-miRNA interaction analysis involving loss of function and gain-of-function experiments, we found that lncRNA PNKY inhibited the binding of miR124 to PTBP1 and maintained the homeostasis of choroidal vascular function by promoting Bcl-2 like protein 11 (BIM), and its dysfunction led to exacerbation of CNV lesion. Therefore, this study suggests that the lncPNKY/PTBP1-miR-124 axis is involved in regulating the development of CNV, providing a potential therapeutic target for the treatment of CNV.

Novel 3D cross-shaped Zn/Co bimetallic zeolite imidazolate frameworks for simultaneous removal Cr(VI) and Congo Red.

The photocatalytic properties of Zn/Co zeolite imidazolate frameworks (ZIF-ZnCo) prepared by various Zn/Co ratio are of significantly diversity due to the morphology structure of the ZIF-ZnCo. Thereinto, the prepared ZIF-ZnCO-8:1 is excellent capability by virtue of its 3D cross-shaped structure. Spectral test results show that as-prepared novel 3D cross-shaped ZIF-ZnCo has a lower recombination rate of electron and hole pairs than the lamellar and dodecahedral, thus improving the photocatalytic ability. The photocatalytic ability of 3D cross-shaped ZIF-ZnCo was carefully investigated for removing mixed solution of Congo Red (CR) and Cr(VI). The photocatalytic reduction ability of 3D cross-shaped ZIF-ZnCo was 22% higher than ZIF-8 for Cr(VI). Meanwhile, CR was altogether removed at dark processing and Cr(VI) was removed 70% after dark processing 120 min and photocatalytic 240 min. Therefore, the high adsorption and photocatalytic capacity denote the potential application of 3D cross-shaped ZIF-ZnCo.

Circular RNA-ZBTB44 regulates the development of choroidal neovascularization.

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.

Microarray Analysis of circRNA Expression Pattern in Corneal Neovascularization.

PURPOSE: To identify differentially expressed circular RNAs (circRNAs) in corneal neovascularization. METHODS: We established an alkali burn-induced corneal neovascularization model and performed circRNA expression profiling to identify differentially expressed circRNAs between avascular corneas and vascularized corneas. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses of the host genes of dysregulated circRNAs were performed to determine the related biological modules and pathological pathways. Real-time polymerase chain reactions were performed to detect the expression pattern of circRNAs in the clinical samples. In vitro experiments were performed to determine the role of circRNAs in vascular endothelial angiogenic effects. RESULTS: Two hundred twenty-nine circRNAs were differentially expressed between avascular corneas and vascularized corneas. The host genes of dysregulated circRNAs were targeted to cell cycle (biologic process), cytoplasm (cellular component), and protein binding (molecular function). Rap1 signaling was identified as the most enriched signaling pathway. Clinical studies showed that the human ortholog of cZFP609 and cKifap3 was dysregulated in the vascularized human corneas. cKifap3 silencing facilitated vascular endothelial angiogenic effects by regulating endothelial cell proliferation, migration, and tube formation. CONCLUSIONS: This study suggests that circRNAs are involved in the pathogenesis of corneal neovascularization. cZFP609 and cKifap3 may serve as promising targets for the treatment of corneal neovascularization.

Development of a combination microbicide gel formulation containing IQP-0528 and tenofovir for the prevention of HIV infection.

In light of the increasing worldwide AIDS pandemic, there is a continuing need to develop new prevention strategies to inhibit the transmission of HIV-1. In the absence of a successful vaccine, topical microbicides represent the best strategies to reduce the epidemic. Following the success of HIV therapeutic cocktail strategies, combinations of microbicides including nucleotide reverse transcriptase inhibitors (NtRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) may offer significant protection from infection over single agents. We have developed a combination microbicide gel formulation for the delivery of IQP-0528, a novel NNRTI, and tenofovir (TFV), a NtRTI. Gel formulations were evaluated based on quantitative viscoelastic and physiochemical evaluations defined by a target product profile (TPP). For the majority of the evaluations, the gel formulations behaved similarly; all showed shear thinning behavior, were stable, nontoxic, and active against HIV-1 infection. Gel formulation F2759 displayed increased drug release of 289 ± 100 µg/(cm(2) h(1/2) ) and a tissue permeability of 60 times the half maximal effective concentration (EC(50) ) of TFV and 800 times the EC(50) of IQP-0528. In addition, F2759 showed osmolality within TPP and the highest performance in gel spreading. We have identified a gel formulation to deliver a combination microbicide of IQP-0528 and TFV that has significant potential to prevent infection of HIV-1.

Biodegradable nanoparticle flocculates for dry powder aerosol formulation.

Uncontrolled agglomeration presents a formidable encumbrance to nanoparticle formulation as a dry powder for inhalation therapy. Spray-drying and freeze-drying of nanosuspensions has demonstrated some success in creating dry powders composed of agglomerated nanoparticles with appropriate aerodynamic properties. These controlled drying processes, however, may require an undesirable amount of excipient to maintain an active therapeutic while generating dry powders and may not offer the desired control over agglomerate size and aerosolizability. As a potential alternative approach, a method for flocculating nanoparticles in solution followed by freeze-drying is reported. Biodegradable poly(DL-lactic-co-glycolic acid) nanoparticles were self-assembled into flocs via electrostatic interactions between nanoparticles coated with oppositely charged polyelectrolytes. The size of the nanoparticle flocs was readily controlled by manipulating the mixing ratio of charged nanoparticles. Freeze-drying the flocculated nanoparticles produced dry powders exhibiting low density (approximately 0.1 g/cm3), a weblike morphology, and desirable aerodynamic properties suited for dry powder aerosols.

Acid-Labile Polyvinylamine Micro- and Nanogel Capsules.

Hollow nanoparticles represent an emerging area of development for the encapsulation of active ingredients. Expanding the capabilities of these nanomaterials will require continued efforts to infill properties such as size control, biodegradability, and environmental responsiveness. Acid-labile poly(N-vinylformamide) (PNVF) nanocapsules were synthesized by free radical polymerization of N-vinylformamide on the surface of silica nanoparticles. Polymerization in the presence of a novel crosslinker that contains an acid-labile ketal facilitated stable etching of silica nanoparticle templates using sodium hydroxide and recovery of degradable PNVF nanocapsules. The formamido side group of PNVF was then hydrolyzed by extended exposure to sodium hydroxide to produce polyvinylamine (PVAm) micro- and nanocapsules. Both capsule types demonstrated an increasing dissolution rate as pH decreased. In addition, PVAm nanocapsules exhibited swelling in proportion to the relative charge density of the PVAm network (a function of the degree of formamide hydrolysis and pH), presumably due to the repulsion of positively charged amino groups within the elastic shell network. The synthetic approaches reported provide methods to endow nanocapsules with key attributes such as size control, pH sensitive degradation, swelling in response to pH, and amine functionality.

A general photonic crystal sensing motif: creatinine in bodily fluids.

We developed a new sensing motif for the detection and quantification of creatinine, which is an important small molecule marker of renal dysfunction. This novel sensor motif is based on our intelligent polymerized crystalline colloidal array (IPCCA) materials, in which a three-dimensional crystalline colloidal array (CCA) of monodisperse, highly charged polystyrene latex particles are polymerized within lightly cross-linked polyacrylamide hydrogels. These composite hydrogels are photonic crystals in which the embedded CCA diffracts visible light and appears intensely colored. Volume phase transitions of the hydrogel cause changes in the CCA lattice spacings which change the diffracted wavelength of light. We functionalized the hydrogel with two coupled recognition modules, a creatinine deiminase (CD) enzyme and a 2-nitrophenol (2NPh) titrating group. Creatinine within the gel is rapidly hydrolyzed by the CD enzyme in a reaction which releases OH(-). This elevates the steady-state pH within the hydrogel as compared to the exterior solution. In response, the 2NPh is deprotonated. The increased solubility of the phenolate species as compared to that of the neutral phenols causes a hydrogel swelling which red-shifts the IPCCA diffraction. This photonic crystal IPCCA senses physiologically relevant creatinine levels, with a detection limit of 6 microM, at physiological pH and salinity. This sensor also determines physiological levels of creatinine in human blood serum samples. This sensing technology platform is quite general. It may be used to fabricate photonic crystal sensors for any species for which there exists an enzyme which catalyzes it to release H(+) or OH(-).

Synthesis of poly(maleimide-co-2-ethylacrylic acid) and its properties of suppressing metastasis and growth of carcinoma.

A series of copolymers is prepared using maleimide and 2-ethylacrylic acid as comonomer. This kind of copolymer shows low toxicity (LD50: 601-798 mg/kg) and significant curative effect on Lewis lung carcinoma and S180.