Relationship between nonperfusion area from widefield optical coherence tomography angiography and macular vascular parameters in diabetic retinopathy.

PURPOSE: To evaluate the relationship between the nonperfusion area (NPA) from widefield optical coherence tomography angiography (OCTA) and macular vascular parameters in diabetic retinopathy (DR). METHODS: In total, 51 eyes from 51 patients with proliferative DR (PDR) or moderate/severe non-PDR were included. Widefield OCTA using the Zeiss Plex Elite 9000 was performed. A semi-automatic algorithm calculated the percentages of the NPA within the total image. Macular OCTA (3 × 3 mm and 6 × 6 mm area) was scanned using the RTVue-XR Avanti. Vessel density (VD) was automatically separated into the superficial (SCP) and deep capillary plexus (DCP), and foveal avascular zone (FAZ) measurements were computed according to the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. RESULTS: A negative correlation was found between the average VD of the SCP and DCP obtained 3 × 3 mm and 6 × 6 mm area and the NPA. Multiple regression analysis revealed that the temporal-perifoveal region most negatively correlated with the NPA (r = - 0.55, p < 0.0001). No correlation was found between FAZ measurements and DR severity (area, p = 0.07; perimeter, p = 0.13). CONCLUSION: Diabetic macular nonperfusion was significantly associated with the NPA from widefield OCTA. In particular, the temporal-perifoveal DCP disorder may be a sensitive indicator of wide NPA.

Cellulose Nanocrystal Embedded Composite Foam and Its Carbonization for Energy Application.

In this study, we fabricated a cellulose nanocrystal (CNC)-embedded aerogel-like chitosan foam and carbonized the 3D foam for electrical energy harvesting. The nanocrystal-supported cellulose foam can demonstrate a high surface area and porosity, homogeneous size ranging from various microscales, and a high quality of absorbing external additives. In order to prepare CNC, microcrystalline cellulose (MCC) was chemically treated with sulfuric acid. The CNC incorporates into chitosan, enhancing mechanical properties, crystallization, and generation of the aerogel-like porous structure. The weight percentage of the CNC was 2 wt% in the chitosan composite. The CNC/chitosan foam is produced using the freeze-drying method, and the CNC-embedded CNC/chitosan foam has been carbonized. We found that the degree of crystallization of carbon structure increased, including the CNCs. Both CNC and chitosan are degradable materials when CNC includes chitosan, which can form a high surface area with some typical surface-related morphology. The electrical cyclic voltammetric result shows that the vertical composite specimen had superior electrochemical properties compared to the horizontal composite specimen. In addition, the BET measurement indicated that the CNC/chitosan foam possessed a high porosity, especially mesopores with layer structures. At the same time, the carbonized CNC led to a significant increase in the portion of micropore.

Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells.

Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.

Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort. Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort. Results: A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 µm; P = 0.001-0.038) and marginally associated with decreased SFCT in Malays (-12.7 to -20.6 µm; P = 0.014-0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-µm reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-µm increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (-20.2 to -25.8 µm; P = 0.003-0.027). Conclusions: CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.

Characterization of Phase Change Materials Fabricated with Cross-Linked Graphene Aerogels.

3D porous graphene aerogel exhibits a high surface area which can hold plenty of pure phase change material (PCM) into the internal space. In order to maintain the flexibility of PCM without volume shrinkage under the external force, cross-linked graphene aerogel was prepared by the cysteamine vapor method. The cross-linked graphene aerogel had a high stress-strain durability and chemical stability for infiltrating PCM to produce a form-stable PCM composite. The latent heat of PCM is one of the elements to estimate the capacity of PCM thermal energy storage (TES) during the phase transition process. The cross-linked graphene aerogel-supported PCM composite showed a great TES to be utilized in thermal-to-electrical energy harvesting. The cross-linked graphene aerogel also had an excellent mechanical property of preventing damage at a high temperature.

Phase Change Material (PCM) Composite Supported by 3D Cross-Linked Porous Graphene Aerogel.

Integration of form-stable phase change material (PCM) composites with a pyro system can provide sufficient electrical energy during the light-on/off process. In this work, modified 3D porous graphene aerogel is utilized as a reliable supporting material to effectively reduce volume shrinkage during the infiltration process. Poly(vinylidene difluoride) (PVDF) is used for a transparent pyro film in the pyro system. The temperature fluctuation gives rise to a noise effect that restricts the generation of energy harvesting. The cross-linked graphene aerogel consisting of PCM composites can stabilize the temperature fluctuation in both melting and cooling processes. This shows that PCM composites can be applied to the pyro system under the change of the external environment. To evaluate the experimental results, a numerical simulation was conducted by using the finite element method (FEM).

Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation.

AIM: To investigate changes in extracellular matrix (ECM) gene expression in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation. METHODS: HTM cells were grown on a glass plate coated with 0.02% type I collagen (COL) and exposed to shear stress (0, 0.2, 1.0 dyne/cm2) for 12h. Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction. Phosphorylation of Smad2 protein was investigated by Western blotting. RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control (P<0.05, <0.05, and <0.01, respectively). The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control (P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not significant. The phosphorylation of Smad2 levels was significantly higher compared to the static control cells. CONCLUSION: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical stimulation. The mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

Analysis of Thermoelectric Energy Harvesting with Graphene Aerogel-Supported Form-Stable Phase Change Materials.

Graphene aerogel-supported phase change material (PCM) composites sustain the initial solid state without any leakage problem when they are melted. The high portion of pure PCM in the composite can absorb or release a relatively large amount of heat during heating and cooling. In this study, these form-stable PCM composites were used to construct a thermoelectric power generator for collecting electrical energy under the external temperature change. The Seebeck effect and the temperature difference between the two sides of the thermal device were applied for thermoelectric energy harvesting. Two different PCM composites were used to collect the thermoelectric energy harvesting due to the different phase transition field in the heating and cooling processes. The graphene nano-platelet (GNP) filler was embedded to increase the thermal conductivities of PCM composites. Maximum output current was investigated by utilizing these two PCM composites with different GNP filler ratios. The thermoelectric energy harvesting efficiencies during heating and cooling were 62.26% and 39.96%, respectively. In addition, a finite element method (FEM) numerical analysis was conducted to model the output profiles.

Optorheological Characteristics of Photosynthetic Bacterium Suspension.

Understanding the rheological behavior of materials is of great importance in science. Here, we report a microscopic foundation for optorheology by manipulating the rheological feature through light. A new phenomenon is observed in the photosynthetic bacterial suspension, that the fluid viscosity changes by light-induced electrons. Type IV pili of photosynthetic bacteria is found, and it allows the electron to transport through the exterior of cells and changes the surface potential of cells, which causes an adjustment in the spatial arrangement of cells in the suspension. When an external electric field is applied, the electric dipole of the cells is induced and their dispersion is changed. The rheological properties are measured to evaluate the internal structure of the suspension depending on the light. The photoelectrons enhance the dispersion of the photosynthetic bacteria in the solution, thus leading to a significant increment in the viscosity. We envision that this discovery will provide new applications to the interface of optics, bioengineering, and rheology.

Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus.

Objective: Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model. Methods: To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib. Results: Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway. Conclusions: The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.

Fabrication and Analysis of Sepiolite/Glass Microcapsules/Liquid Crystal Polymer Composites.

Liquid crystal polymer (LCP) composites filled with sepiolite and glass microcapsules were prepared by melt compounding. The composites were extruded using a twin-screw extruder and injection-molded. The objective of this study is to check a possibility of producing a polymeric composite with a low dielectric constant. Physical characteristics of the composites, such as morphological, rheological, mechanical, and electrical properties were analyzed. In particular, the glass microcapsule-reinforced LCP composites showed a significant improvement in lowering the dielectric constant due to its high air content. Additionally, sepiolite could act as an effective filler to improve the mechanical properties of the composites.

Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study.

PURPOSE: Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. STUDY DESIGN: Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. METHODS: Participants were 171 Japanese schoolchildren aged 6 to 12 years, with progressive myopia, spherical equivalence (SE) of -1.00 to -6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24 months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. RESULTS: Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, -1.26 D (95% confidence interval [CI]: -1.35, -1.17) and 0.63 mm (0.59, 0.67) for atropine and -1.48 D (- 1.57, -1.39) and 0.77 mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P < 0.001) for SE and - 0.14 mm (-0.20, -0.08; P < 0.001) for AL. Three patients experienced mild allergic conjunctivitis side effects, with no inter-group difference in incidence (atropine: 2.4%; 2/84 patients; placebo: 1.4%; 1/84 patients). CONCLUSION: With good compliance, 0.01% atropine is effective and safe for preventing the progression of childhood myopia.

Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3.

BACKGROUND: Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus. METHODS: 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization. RESULTS: Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro. CONCLUSIONS: Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.

Fabrication and Characterization of Aluminum Nanoparticle-Reinforced Composites.

With the expanding use of polymers in modern our lives, there is an increasing need to manufacture advanced engineering polymeric parts in a systematic and inexpensive way. Herein, we developed an organic inorganic hybrid composite material with excellent mechanical properties by enhancing the dispersion and moldability of fillers. For this, we prepared and analyzed the physical properties of acrylonitrile butadiene styrene (ABS)/aluminum nanoparticle composites. Al nanoparticles of various sizes (20 nm and 40 nm) and concentrations (3, 6, 9, and 12 wt.%) were employed. The mechanical properties of the prepared composites were measured using a universal testing machine. Rheological and thermal analyses for the composites were carried out with use of a rheometer and a differential thermal calorimeter (DSC). We also conducted optical, chemical, electrical, and morphological property studies of the samples in order to help design and produce high-performance engineering products.

Effective Dispensing Methods for Loading Drugs Only to the Tip of DNA Microneedles.

Here, we propose a novel and simple method to efficiently capture the diffusion of fluorescein isothiocyanate (FITC)-dextran from a biocompatible substance and load the drug only to the tip of DNA microneedles. A dispensing and suction method was chosen to fabricate the designed microneedles with efficient amounts of FITC as the drug model. Importantly, the vacuum process, which could influence the capturing of FITC diffusion from the tip, was evaluated during the manufacturing process. In addition, the simulations were consistent with the experimental results and showed apparent diffusion. Moreover, dextrans of different molecular weights labeled with FITC were chosen to fabricate the tip of microneedles for demonstrating their applicability. Finally, a micro-jetting system with a micro-nozzle (diameter: 80 µm) was developed to achieve the accurate and rapid loading of small amounts of FITC using the anti-diffusion and micro-jetting methods. Our method not only uses a simple and fast manufacturing process, but also fabricates the tips of microneedles more efficiently with FITC compared with the existing methods. We believe that the proposed method is essential for the clinical applications of the microneedle drug delivery platform.

Intrahepatic cholangiocarcinomas with IDH1/2 mutation-associated hypermethylation at selective genes and their clinicopathological features.

Intrahepatic cholangiocarcinoma (ICC) is a rare but fatal tumor. The isocitrate dehydrogenase 1 and 2 (IDH1/2) genes are known to be mutated in ICC. IDH1/2 mutations tend to be accompanied by enhanced hypermethylation at a subset of genomic loci. We sought to clarify the clinicopathological features, including prognostic value, of ICCs with IDH1/2 mutation-associated hypermethylation at a subset of genes. The mutation status of IDH1/2 and methylation status of 30 gene CpG island loci were analyzed in 172 cases of ICC using pyrosequencing and the MethyLight assay, respectively. The mutation status of IDH1/2 was correlated with clinicopathological features and the DNA methylation status at 30 gene loci. Then, the clinicopathological characteristics were analyzed regarding three-tiered methylation statuses in genes showing IDH1/2 mutation-associated methylation. IDH1/2 mutations were found in 9.3% of ICCs, and IDH1/2-mutated tumors were associated with the histological subtype, including the bile ductular type and small duct type, and poor differentiation. Eight DNA methylation markers showed associations with IDH1/2 mutations, and ICCs with > 5/8 methylated markers were associated with the bile ductular type or small duct type, absence of mucin production, absence of biliary intraepithelial neoplasia, and presence of chronic liver disease. > 5/8 methylated markers were an independent prognostic marker associated with better survival in both cancer-specific survival and recurrence-free survival. In summary, by analyzing the association between IDH1/2 mutations and DNA methylation in individual genes, we developed a panel of DNA methylation markers that were significantly associated with IDH1/2 mutations and were able to identify a subset of ICC with better clinical outcomes.

Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using OCT angiography.

PURPOSE: It has been reported that peripapillary loops develop after central retinal artery occlusion (CRAO). Although cilioretinal anastomoses have been shown by fluorescein angiography (FA) and indocyanine green angiography, these examinations cannot confirm the structural continuity between the retinal arteries and the posterior ciliary arteries. In the current report, we followed a patient with iatrogenic CRAO in which circumpapillary collaterals formed and assessed the connection between these two vascular systems using optical coherence tomography angiography (OCTA). OBSERVATION: Iatrogenic CRAO developed in the left eye of a 30-year-old woman during preoperative embolization of a convexity meningioma. FA and OCTA showed complete impairment of the retinal circulation. Two weeks after this event, OCTA images showed flow in the retinal vessels and the beginning of collateral vessel development on the optic disc margin. Six months later, OCTA images showed that these circumpapillary collaterals connected branches of the retinal arteries with the vessels supplying the optic disc, which originate from the posterior ciliary arteries. CONCLUSION AND IMPORTANCE: OCTA aided our understanding of the three-dimensional configuration of the circumpapillary collaterals that developed after iatrogenic CRAO, which included anastomosis of the retinal and posterior ciliary artery systems. OCTA is useful for noninvasively monitoring the status of retinal circulatory dynamics after iatrogenic CRAO.

A Broadband Multiplex Living Solar Cell.

Developing renewable and sustainable energy sources is a compelling goal in materials science and engineering. In particular, natural photosynthesis with its infinite energy reservoir provides profound inspiration for energy conversion and storage systems. Here, we report a multiplex living solar cell that offers a drastic power enhancement by harnessing the broadband spectra of the visible wavelength range for photosynthesis. Cyanobacteria are embedded into a nanostructural complex composed of Au nanoparticles (NPs) and ZnO nanorods (NRs). This nanocomposite system is capable of not only generating excitons but also amplifying the photosynthetic performance of the cell via a far-field scattering effect in the broadband region of the light, resulting in multiplex energy harvesting with a peak power density of 6.15 mW/m2. We envision that this study will provide a strategic way to enhance the performance of biophotovoltaics, enabling efficient and durable energy generation.

Carrier transport of all carbonized ß-glucosic eco-materials.

Attempts have been made to bring eco-friendly biomaterials into high-end electronic devices that require both high performance and durability. Polysaccharides, glycosidically linked monosaccharide units, are of particular interest because they serve as a promising material, owing to their environmentally friendly and adaptable features. We used a carbonized polysaccharide eco-material encompassing nanoparticles and chitosan to study the carrier-transport behavior of ß-glucosic materials. Chitosan composites incorporating nanoparticles were prepared and then carbonized to control the crystal structure of the material. Three kinds of metal-insulator-metal devices were fabricated using carbonized materials, and their carrier-transport properties were analyzed. The results showed that the addition of cellulose nano-whiskers (CNWs) into chitosan leads to a more ordered carbon structure, increasing the charge transport in the carbonized material. We anticipate that carbonizing nanoparticle dispersed green composites provides a new pathway for the development of sustainable and environmentally benign material systems.

Improved performance of carbon nanotubes embedded photomicrobial solar cell.

Enhancing the energy efficiency of power out is a key issue of microorganisms based energy harvesting. Here, we introduced carbon nanotubes (CNTs) into a photomicrobial solar cell (PMSC) system in order to increase the harvesting energy power. Microcystis aeruginosa was used as a solar energy converter, microorganism. It revealed that when a small amount of CNTs (e.g. 0.001 wt%) were added in the cyanobacterium suspension, the photocurrents were enhanced dramatically. The optical and electrical properties of the CNT suspension were analyzed. The biochemical features of the PMSC were evaluated under dark and light conditions. This study is expected to offer a strategic way for harvesting living cell-based solar energy in a more efficient manner.