Cerium Methacrylate Assisted Preparation of Highly Thermally Conductive and Anticorrosive Multifunctional Coatings for Heat Conduction Metals Protection.

Preparing polymeric coatings with well corrosion resistance and high thermal conductivity (TC) to prolong operational life and ensure service reliability of heat conductive metallic materials has long been a substantive and urgent need while a difficult task. Here we report a multifunctional epoxy composite coating (F-CB/CEP) by synthesizing cerium methacrylate and ingeniously using it as a novel curing agent with corrosion inhibit for epoxy resin and modifier for boron nitride through "cation-π" interaction. The prepared F-CB/CEP coating presents a high TC of 4.29 W m-1 K-1, which is much higher than other reported anti-corrosion polymer coatings and thereby endowing metal materials coated by this coating with outstanding thermal management performance compared with those coated by pure epoxy coating. Meanwhile, the low-frequency impedance remains at 5.1 × 1011 Ω cm2 even after 181 days of immersion in 3.5 wt% NaCl solution. Besides, the coating also exhibits well hydrophobicity, self-cleaning properties, temperature resistance and adhesion. This work provides valuable insights for the preparation of high-performance composite coatings with potential to be used as advanced multifunctional thermal management materials, especially for heat conduction metals protection.

Inhibition of vascular endothelial growth factor alleviates neovascular retinopathy with regulated neurotrophic/proinflammatory cytokines through the modulation of DBI-TSPO signaling.

Diazepam binding inhibitor (DBI)-translocator protein (18kDa) (TSPO) signaling in the retina was reported to possess coordinated macroglia-microglia interactions. We investigated DBI-TSPO signaling and its correlation with vascular endothelial growth factor (VEGF), neurotrophic or inflammatory cytokines in neovascular retinopathy, and under hypoxic conditions. The vitreous expression of DBI, VEGF, nerve growth factor (NGF), and interleukin-1beta (IL-1ß) were examined in proliferative diabetic retinopathy (PDR) patients with or without anti-VEGF therapy and nondiabetic controls. Retinal DBI-TSPO signaling and the effect of the anti-VEGF agent were evaluated in a mouse model of oxygen-induced retinopathy (OIR). Interactions between Müller cell-derived VEGF and DBI, as well as cocultured microglial cells under hypoxic conditions, were studied, using Western blot, real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunofluorescent labeling. Results showed that vitreous levels of DBI, VEGF, NGF, and IL-1ß were significantly higher in PDR patients compared with controls, which further changed after anti-VEGF therapy. A statistical association was found between vitreous DBI and VEGF, NGF, IL-1ß, and age. The application of the anti-VEGF agent in the OIR model induced retinal expression of DBI and NGF, and attenuated inflammation and microglial cell activation. Inhibition of Müller cell-derived VEGF could increase its DBI expression under hypoxic conditions, while the DBI-TSPO signaling pathway is essential for anti-VEGF agents exerting anti-inflammatory and neuroprotective effects, as well as limiting inflammatory magnitude, promoting its neurotrophin production and anti-inflammatory (M2) polarization in microglial cells. These findings suggest the beneficial effect of anti-VEGF therapy on inflammation and neurotrophy of retinal glial cells through modulation of the DBI-TSPO signaling pathway.

CXCL16/ERK1/2 pathway regulates human podocytes growth, migration, apoptosis and epithelial mesenchymal transition.

Primary nephrotic syndrome (PNS) is the commonest glomerular disease affecting children. Previous studies have confirmed that CXC motif chemokine ligand 16 (CXCL16) is involved in the pathogenesis of PNS. However, the exact mechanisms underlying the pathogenesis of PNS remain to be elucidated. Thus, the present study aimed to elucidate the role of CXCL16 in PNS. It was found that the expression of CXCL16 and extracellular signal­regulated kinases 1 and 2 (ERK1/2) were significantly increased in clinical PNS renal tissues using reverse transcription­quantitative PCR, western blot analysis and immunohistochemistry. Lentivirus overexpression or short hairpin RNA vector was used to induce the overexpression or knockdown of CXCL16 in podocytes, respectively. Overexpression of CXCL16 in podocytes could decrease the cell proliferation and increase the migration and apoptosis, whereas CXCL16 knockdown increased cell proliferation and decreased cell migration and apoptosis. Results of the present study further demonstrated that ERK2 protein expression was regulated by CXCL16. The knockdown of ERK2 expression reversed the effects of CXCL16 on the proliferation, apoptosis, migration and epithelial mesenchymal transition (EMT) of podocytes. Collectively, the findings of the present study highlighted that the CXCL16/ERK1/2 pathway regulates the growth, migration, apoptosis and EMT of human podocytes.

P2X7R antagonist protects against renal injury in mice with adriamycin nephropathy.

Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis. Therefore, the current study aimed to explore the mechanism of P2X7R in renal injured mice with adriamycin (ADR) nephropathy. The protective effect of a P2X7R antagonist on the kidneys of mice with ADR nephropathy was also evaluated. Nephropathy was induced by a single intravenous injection of ADR (10.5 mg/kg). A total of 6 h before the model was established, the P2X7R antagonist A438079 (100, 200 and 300 µmol/kg) was injected into the mice, which was subsequently administered daily for 1 week by intraperitoneal injection. Subsequently, all mice were sacrificed, after which blood, 24 h-urine and the kidneys were collected. The levels of albumin (ALB) and total cholesterol (TC) in the serum, along with urine protein content at 24 h were determined using an automatic biochemical analyzer. The levels of IL-1ß and IL-18 were additionally detected in the renal tissues by ELISA. Moreover, the expression of P2X7R, oxidized (ox)-low density lipoprotein (LDL), C-X-C motif chemokine ligand 16 (CXCL16), Bax, caspase-3 and NLRP3 in renal tissues was detected by immunohistochemistry. Apoptosis in the renal tissues was observed using the TUNEL assay. The results demonstrated that compared with the control group, decreased weight, increased proteinuria, decreased serum ALB and increased serum TC was observed in the ADR group. The expression of IL-1ß, IL-18, P2X7R, ox-LDL, CXCL16, Bax, caspase-3 and NLRP3, as well as cellular apoptosis in the renal tissues of the ADR group, was significantly increased in the ADR group compared with the control. However, compared with the ADR group, the changes in all indices in the ADR + A438079 groups were attenuated. Overall, P2X7R, ox-LDL and CXCL16 may be associated with ADR nephropathy, while inhibition of P2X7R may reduce the expression of ox-LDL by downregulating the CXCL16 pathway to alleviate kidney injury in mice with ADR nephropathy. Furthermore, activated P2X7R may promote the release of inflammatory cytokines IL-1ß and IL-18 through the downstream P2X7R/NLRP3 pathway and upregulate the expression of Bax and caspase-3 to promote apoptosis, which participates in the process of ADR nephropathy. Inhibiting P2X7R may also reduce the release of IL-1ß and IL-18 by downregulating the P2X7R/NLRP3 pathway, downregulating the expression of Bax and caspase-3, and reducing apoptosis, thereby alleviating kidney injury in mice with ADR nephropathy.

P2X7 receptor inhibition attenuates podocyte injury by oxLDL through deregulating CXCL16.

This study aims to evaluate the effect of purinergic ligand-gated ion channel 7 receptor (P2X7R) antagonist A438079 in kidneys of children with primary nephrotic syndrome (PNS). In vitro, human podocytes were respectively stimulated with oxLDL (80 µg/ml), A438079 (10 µmol/L), or the compound oxLDL and A438079 together. CXC chemokine ligand 16 (CXCL16) and P2X7R expression levels were detected by Western blot and immunofluorescence assay, respectively. Immunofluorescence assay was used to detect Dil-oxLDL, and a Colorimetric Cholesterol Detection Kit was used for quantitative determination. Our results demonstrated that CXCL16 and P2X7R expression levels were remarkably increased in the renal tissue from children with PNS, particularly in the same location. Furthermore, in contrast to children with minimal change disease, the expressions of P2X7R and CXCL16 in renal tissue of children with focal segmental glomerulosclerosis were more obvious. In vitro, CXCL16 and P2X7R expression levels in human podocytes stimulated with oxLDL were markedly elevated accompanying higher intracellular lipid accumulation compared with the normal control group. In addition, pretreatment of human podocytes with A438079 before the start of oxLDL stimulation causes a significant reduction in CXCL16 expression and a decrease in lipid accumulation. Overall, CXCL16 and P2X7R may participate in the progression of PNS. The lipid accumulation reduction caused by A438079 may be through deregulating the CXCL16 pathway, suggesting that there is a potential role for P2X7R antagonists to remedy PNS.

Millefeuille-Inspired Thermal Interface Materials based on Double Self-Assembly Technique for Efficient Microelectronic Cooling and Electromagnetic Interference Shielding.

Owing to the increasing power density of miniaturized and high-frequency electronic devices, flexible thermal interface materials (TIMs) with the electromagnetic interference (EMI) shielding property are in urgent demand to maintain the system performance and reliability. Recently, carbon-based TIMs receive considerable attention due to the ultrahigh intrinsic thermal conductivity (TC). However, the large-scale production of such TIMs is restricted by some technical difficulties, such as production-induced defects of graphite sheets, poor microstructure architecture within the matrix, and nonnegligible interfacial thermal resistance result from the strong phono scattering. In this work, inspired by the structure and production process of millefeuille cakes, a unique double self-assembly strategy for fabricating ultrahigh thermal conductive TIMs with superior EMI shielding performance is demonstrated. The percolating and oriented multilayered microstructure enables the TIM to exhibit an ultrahigh in-plane TC of 233.67 W m-1 K-1 together with an outstanding EMI shielding effectiveness of 79.0 dB (at 12.4 GHz). In the TIM evaluation system, a nearly 45 °C decrease is obtained by this TIM when compared to the commercial material. The obtained TIM achieves the desired balance between thermal conduction and EMI shielding performance, indicating broad prospects in the fields of military applications and next-generation thermal management systems.

The IL-23/IL-17 axis promotes the formation of retinal neovascularization by activating the NLRP3 inflammasome in macrophages in an experimental retinopathy mouse model.

Retinal neovascularization (RNV), a pathological process shared among diabetic retinopathy, retinopathy of prematurity and other retinopathies, has been widely studied, but the mechanism remains unclear. In this study, the mechanism by which the interleukin (IL)-23/IL-17 axis regulates RNV in oxygen-induced retinopathy (OIR) model mice and in cell experiments in vitro was characterized. In the retinas of OIR mice, IL-23/IL-17 axis activation was increased and regulated RNV formation, and this effect was accompanied by increased macrophage recruitment and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome activation. Moreover, inhibiting the IL-23/IL-17 axis reduced the number of macrophage and the expression and activation of NLRP3 inflammasome. On the other hand, recombinant (r) IL-23p19 and rIL-17A promoted the expression and activation of NLRP3 inflammasome, and the proliferation and migration of macrophages. Furthermore, macrophage elimination decreased the activation of IL-23/IL-17 axis and the expression and activation of NLRP3 inflammasome. In summary, our experiments showed that the IL-23/IL-17 axis promoted the formation of RNV by activating the NLRP3 inflammasome in retinal macrophages of an OIR mouse model.

Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization.

PURPOSE: The formation of retinal neovascularization (RNV) is the primary pathological process underlying retinopathy of prematurity (ROP). Previous studies have shown that inflammatory factors are related to the formation of RNV. Tumor necrosis factor-α (TNF-α), as an important factor in the inflammatory response, is involved in the regulation of RNV formation. However, the mechanism through which TNF-α inhibition reduces RNV formation is not fully clarified. Therefore, the purpose of this study was to explore the effect of etanercept, an inhibitor of TNF-α, on RNV, and its possible mechanism. METHODS: In vivo, an oxygen-induced retinopathy (OIR) mouse model was used to determine the effect of etanercept on the formation of RNV by performing immunostaining. The effect of etanercept on tumor necrosis factor receptor-associated factor 2 (TRAF2), pro-angiogenic-related factors, and pro/anti-inflammatory factors in OIR mice was assessed by real-time PCR and Western blotting. In vitro, the effect of etanercept on TNF-α-induced human retinal microvascular endothelial cell tube formation was evaluated by tube formation assays, and the potential mechanism of etanercept was explored by Western blotting. RESULTS: In vivo, etanercept reduced the area of RNV and decreased the expression of TRAF2 in the OIR mouse model. Etanercept also suppressed the expression of several pro-angiogenic factors and regulated the pro/anti-inflammatory factors. In vitro, etanercept reduced endothelial cell tube formation by inhibiting activation of the NF-κB signaling pathway. CONCLUSION: Etanercept can regulate pro/anti-inflammatory factors and reduce the expression of pro-angiogenic factors by inhibiting NF-κB phosphorylation, thereby reducing RNV formation.

Evaluation of retinal and choroidal variations in thyroid-associated ophthalmopathy using optical coherence tomography angiography.

BACKGROUND: To investigate the difference in retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT) and superficial retinal vessels between thyroid-associated ophthalmopathy (TAO) patients and healthy controls. To identify the potential influencing factors for these parameters and evaluate their diagnostic abilities in TAO. METHODS: Twenty active TAO patients, 33 inactive TAO patients and 29 healthy participants were enrolled. TAO patients were divided according to the clinical activity score (CAS). RNFL thickness and CT were measured by HD-OCT, while foveal avascular zone (FAZ), vascular density and perfusion density were measured by optical coherence tomography angiography (OCTA). SPSS software was used for statistical analysis. RESULTS: Active TAO patients had thinner RNFL thickness than the other two groups (P < 0.001, P < 0.001). Both active and inactive TAO patients had significantly higher CT in the macular region (all P < 0.05). The FAZ area in the active TAO group was significantly larger than the other two groups (P = 0.045, P = 0.001). The inactive TAO group had significantly higher vascular density than the other two groups (all P < 0.05). With regard to the perfusion density, significant differences were observed in the temporal and inferior areas (P = 0.045, P = 0.001), as well as the average values (P = 0.032). The FAZ area was positively correlated with intraocular pressure (r = 0.274, P = 0.013), while it was negatively correlated with axial length (r = - 0.344, P = 0.002). The vascular density and perfusion density were not significantly correlated with different clinical variables (all P > 0.05). The AUC analysis indicated these parameters also exhibited a significant discriminatory power in TAO diagnosis. CONCLUSIONS: TAO patients had significant variations in RNFL thickness, choroidal thickness, FAZ area and superficial retinal vessels. These parameters appeared to be potential adjuncts in the evaluation of TAO patients.

Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1ß/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model.

Activation of the nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome plays an important role in ocular neovascularization. In our study, we found that the expression and activation levels of NLRP3 inflammasome components, including NLRP3, an apoptosis-associated speck-like protein (ASC) containing caspase activation and recruitment domain (CARD) and caspase-1 (CAS1), were significantly upregulated. In addition, we found interleukin (IL)-1ß activity increased while IL-18 activity decreased in the retinas of oxygen-induced ischemic retinopathy (OIR) mice. MCC950, an inhibitor of NLRP3, reversed the IL-1ß/IL-18 activation pattern, inhibited the formation of retinal neovascularization (RNV), decreased the number of acellular capillaries and reduced leakage of retinal vessels. Moreover, MCC950 could regulate the expression of endothelial cell- and pericyte function-associated molecules, such as vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)1, VEGFR2, matrix metalloproteinase (MMP)2, MMP9, tissue inhibitor of metalloproteinases (TIMP)1, TIMP2, platelet-derived growth factor receptor-ß (PDGFR-ß), platelet-derived growth factor-B (PDGF-B), and angiopoietin2 (Ang2). In vitro, recombinant human (r)IL-18 and rIL-1ß regulated the expression of endothelial cell- and pericyte function-associated molecules and the proliferation and migration of endothelial cells and pericytes. We therefore determined that inhibiting the NLRP3 inflammasome with MCC950 can regulate the function of endothelial cells and pericytes by reversing the IL-1ß/IL-18 activation pattern to ameliorate RNV and leakage; thereby opening new avenues to treat RNV-associated ocular diseases.

oxLDL promotes podocyte migration by regulating CXCL16, ADAM10 and ACTN4.

Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in the pediatric population. Hyperlipidemia is one of the main features of NS. The present study investigated the role of CXC motif chemokine ligand 16 (CXCL16) and ADAM metallopeptidase domain 10 (ADAM10) in oxidized low­density lipoprotein (oxLDL)­stimualted podocytes and the underlying mechanisms. CXCL16 and ADAM10 expression levels in oxLDL­treated podocytes were measured via reverse transcription­quantitative PCR and western blotting. Cell migration assays were conducted to assess the migration of oxLDL­treated podocytes. CXCL16 or ADAM10 overexpression and knockdown assays were conducted. The results indicated that oxLDL stimulation increased ADAM10 and CXCL16 expression levels, and enhanced podocyte migration compared with the control group. Moreover, CXCL16 and ADAM10 overexpression significantly increased podocyte migration and the expression of actinin­α4 (ACTN4) compared with the control groups. By contrast, CXCL16 and ADAM10 knockdown significantly reduced podocyte migration and the expression of ACTN4 compared with the control groups. The results suggested that oxLDL promoted podocyte migration by regulating CXCL16 and ADAM10 expression, as well as by modulating the actin cytoskeleton. Therefore, CXCL16 and ADAM10 may serve as novel therapeutic targets for primary nephrotic syndrome in children.

A sustainable dynamic redox reaction passive film for long-term anti-corrosion of carbon steel surface.

CeO2 was used as the only oxidant for aniline polymerization, and polyaniline (PANI) was grown on CeO2 surface to form CeO2@PANI nanocomposites. SEM and TEM showed that the CeO2@PANI composites were nanorods in a core-shell structure. XPS indicated that CeO2-core was reduced by aniline into Ce3+, which was then captured by the PANI-shell. Then the passive ability of CeO2@PANI coating on steels was explored. EIS showed that the impedance modulus of the CeO2@PANI coating exceeded 108 Ω·cm2 after accelerated immersion. The SVET and XPS confirmed that PANI polarized the anodic reaction, Ce3+ suppressed the cathodic reaction, and PO43- formed complex precipitation. Some high-valent metal oxides can directly oxidize the aniline polymerization to form MO@PANI hybrid particles. The cations obtained by the metal oxide reduction can be captured by PANI and participate in passivation together with dopants. This study provides a new kind of nanocomposite fillers that can effectively passivate steel substrates within epoxy coatings for long-time protection.

Inhibiting NF-κB Signaling Activation Reduces Retinal Neovascularization by Promoting a Polarization Shift in Macrophages.

Purpose: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling is involved in regulating tumor angiogenesis and metastasis; however, the exact mechanism of action in retinal neovascularization (RNV) remains unclear. The purpose of this study was to determine the role and underlying mechanism of NF-κB in regulating RNV in retinal neovascularization mice. Methods: Expression levels of NF-κB signaling were detected by immunofluorescence staining and western blotting in retinas of oxygen-induced retinopathy (OIR) mice. OIR mice were treated with either pyrrolidinedithiocarbamate (PDTC), a NF-κB signaling inhibitor, or PBS, and retinal flat-mounts were performed to quantify the area of RNV and the recruitment of retinal macrophages by immunofluorescence staining. Macrophage polarization detected by flow cytometric analysis and the expression of macrophage polarization-associated genes were evaluated by immunofluorescence staining, quantitative RT-PCR, and western blotting. Results: Expression levels of phosphorylated IκBα (p-IκBα) and p-p65 increased in OIR mice. Inhibiting NF-κB signaling activation by PDTC significantly reduced RNV. After treatment with PDTC, a reduction in the quantity of macrophages was observed: M1 polarized macrophages decreased, and M2 polarized macrophages increased; the expression of M1 macrophage-associated cytokines decreased and M2 macrophage-associated cytokines increased in the retinas of OIR mice. Conclusions: Blocking activation of NF-κB signaling reduces RNV by promoting polarization of M1 macrophages to M2 macrophages in OIR mice.

Neutralization of Bombina variegata peptide 8 suppresses retinal neovascularization in two different murine models: The oxygen-induced retinopathy model and the rhodopsin promoter/VEGF transgenic mouse model.

Bombina variegata 8 (Bv8), also known as prokineticin-2 (PK-2), is a potent pro-angiogenic factor. However, its role in retinal neovascularization (RNV) remains unknown. In this study, we explored the role of Bv8 in the pathogenesis of RNV. We found that the expression of Bv8 was significantly increased in two different models of retinal neovascularization: the oxygen-induced retinopathy (OIR) mouse model and the rhodopsin promoter (rho)/VEGF transgenic mouse model. Neutralization of Bv8 by intravitreal injections of its antibody, not only inhibited retinal and subretinal neovascularization but also decreased the mRNA and protein levels of several pro-angiogenic factors. Our in vitro assay showed that recombinant human Bv8 (RhBv8) protein promoted human retinal microvascular endothelial cells (HRECs) tube-formation, cell proliferation and vascular endothelial growth factor receptor 1 (VEGFR1) and receptor 2 (VEGFR2) expression. Our findings suggest that Bv8 could be used as a novel target for the treatment of RNV-related ocular diseases.

Müller cells derived neurotrophin-3 inhibits hypoxia-induced photoreceptor apoptosis via the TrkC/ERK pathway.

Neurotrophin-3 (NT-3), a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC) receptor, has been shown to play a crucial role in proliferation, differentiation, and survival. However, the role of NT-3 in the hypoxia-induced retinopathy has not been investigated extensively. Here, we created a model of hypoxia (1% O2) in vitro and found that hypoxia promoted the apoptosis of mouse cone photoreceptor-derived 661W cells, increased the expression of TrkC and cleaved caspase-3. In contrast, the hypoxia-mediated 661W cell apoptosis was markedly alleviated by co-culturing with primary mouse Müller cells. Further mechanism studies revealed that hypoxia increased the synthesis and secretion of NT-3 by Müller cells, and exogenous NT-3 stimulation increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 by binding to TrkC in 661W cells. Besides, both siRNA knockdown of TrkC expression and incubation with an ERK-specific inhibitor PD98059 triggered apoptosis in hypoxic 661W cells. Altogether, these data suggest that NT-3 originating from Müller cells protects photoreceptors from hypoxia-induced apoptosis through a TrkC/ERK-dependent pathway. Our findings may facilitate future studies on the therapeutic implications of NT-3 in the treatment of hypoxia-relevant retinal diseases.

Ultrahigh-flux (>190,000 L·m-2h-1) separation of oil and water by a robust and durable Cu(OH)2 nanoneedles mesh with inverse wettability.

Single-stage oil/water separation membranes usually suffer from weak chemical stability, susceptible mechanical damage and relatively low permeating flux, and the sophisticated preparation processes also limit their massive utilization. In this work, Cu(OH)2 nanoneedles coated copper mesh (CM) is prepared by simple and eco-friendly anodic oxidation at a current density of 4 mA/cm2 for 6 min, which is the most efficient route reported so far. The mesh exhibits outstanding superhydrophilicity and underwater superoleophobicity towards various oils with contact angles up to 164.9°, achieving superior oil/water separation efficiency of above 99.5% and ultrahigh permeating flux of 191 160 L·m-2h-1 solely driven by gravity. Impressively, the Cu(OH)2/CM demonstrates excellent chemical stability and anti-fouling performance when exposed to acidic and strongly alkaline solutions, saturated NaCl solution and various organic solvents. High durability to withstand mechanical challenges, e.g. high-power sonication and sand abrasion, is experimentally confirmed owing to strong cohesional strength of Cu(OH)2 nanoneedles on CM surface. Importantly, the Cu(OH)2/CM exhibits favorable long-term recyclability with stable microstructure morphologies even after 50 cycles. These distinct advantages endow the Cu(OH)2/CM to be an ideal candidate to efficiently separate oil pollutants from water. The oil/water separation mechanisms are proposed based on the concept of intrusion pressure.

Anti-apoptotic effect of interleukin-17 in a mouse model of oxygen-induced retinopathy.

Retinopathy of prematurity (ROP) is an important cause of visual loss in children born prematurely. Although the involvement of inflammation in the development of ROP is gaining increasing attention, the role of IL-17A in ROP progress remains unclear. The aim of this study was to assess the levels of IL-17A production in the mice model of oxygen-induced retinopathy (OIR) and elucidate its potential roles. Wild-type (WT) and IL-17A knockout (IL-17A-/-) mice were exposed to 75% O2 from postnatal day 7 (P7) to P12. Age-matched controls were maintained in room air. Primary Müller cells isolated from WT or IL-17A-/- mice retina were co-cultured with 661W cells and exposed to hypoxic conditions. Western blotting and immunofluorescent staining were used to assess the expression of target protein. Apoptosis in OIR retinal sections and 661W cells was detected by TUNEL staining. Results turned out that IL-17A expression was increased and reached a peak at P22 in OIR retina and at 8 h in hypoxic-cultured Müller cells. IL-17A knockout decreased the expression of glial fibrillary acidic protein (GFAP) and mature neurotrophin-3 (NT-3) in retina of OIR mice as well as hypoxic-cultured Müller cells. The NT-3 release induced by IL-17 was prevented by an ERK-specific inhibitor. In addition, more apoptosis cells and higher levels of Bax and cleaved caspase-3 was detected in the retina tissues of IL-17A-/- OIR and the 661W cells co-cultured with IL-17A-/- Müller cells. Taken together, our findings suggest that Müller cell was the potential source of IL-17A under the hypoxic conditions. Modulation of the IL-17A/ERK/NT-3 pathway exerts anti-apoptotic effect on photoreceptor cell and may be a novel therapeutic strategy for ROP.

Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis.

The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.

Nanopolyaniline Coupled with an Anticorrosive Graphene as a 3D Film Electrocatalyst for Efficient Oxidation of Toluene Methyl C-H Bonds and Hydrogen Production at Low Voltage.

A graphene-wrapped polyaniline nanoparticles film embedded in carbon cloth (CC/PANI/G) was fabricated and used as a 3D anodic electrocatalyst for oxidation of toluene methyl C-H groups. The methyl C-H bonds can be oxidized effectively at the CC/PANI/G anode with 99.9 % toluene conversion at a low applied voltage of only 1.0 V, which implies low energy input. Importantly, 86.6 % of toluene methyl C-H groups were converted to benzoyl groups (C=O), and hydrogen was produced efficiently at the cathode. The electrocatalytic efficiency at the CC/PANI/G anode was higher at lower voltage (1.0 V) than at higher voltage (1.5 V), and more hydrogen was produced at the corresponding cathode. The synergistic effect between the dynamic redox chemistry of nanoPANI and the excellent conductivity and anticorrosive action of graphene determined the high electrocatalytic efficiency of the oxidation of toluene methyl C-H groups at the CC/PANI/G anode. Owing to the chemical bonding between graphene and PANI, the anticorrosive CC/PANI/G anodic electrocatalyst was durable and effective for oxidation of toluene methyl C-H groups in acidic environment. This approach provides advanced electrode materials for transforming stable chemical bonds (C-H) into useful functional groups (C=O), which will be beneficial for the synthesis of organic intermediates with coupled hydrogen production.

ATN-161 as an Integrin α5ß1 Antagonist Depresses Ocular Neovascularization by Promoting New Vascular Endothelial Cell Apoptosis.

BACKGROUND ATN-161 (Ac-PHSCN-NH2), an antagonist of integrin α5ß1, has shown an important influence in inhibiting tumor angiogenesis and metastasis of other tumor types. However, the mechanism of action of ATN-161 and whether it can inhibit ocular neovascularization (NV) are unclear. This study investigated the role of ATN-161 in regulating ocular angiogenesis in mouse models and explored the underlying signaling pathway. MATERIAL AND METHODS An oxygen-induced retinopathy (OIR) mouse model and a laser-induced choroidal neovascularization (CNV) mouse model were used to test integrin a5b1 expression and the effect of ATN-161 on ocular NV by immunofluorescence staining, Western blot analysis, and flat-mount analysis. The activation of nuclear factor-κB (NF-κB), matrix metalloproteinase-2/9 (MMP-2/9), and cell apoptosis were detected by immunofluorescence staining, Western blot, real-time RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). The cell proliferation was detected by BrdU labeling. RESULTS In OIR and CNV mice, the protein expression level of integrin α5ß1 increased compared with that in age-matched controls. The mice given ATN-161 had significantly reduced retinal neovascularization (RNV) and CNV. Blocking integrin a5b1 by ATN-161 strongly inhibited nuclear factor-κB (NF-κB) activation and matrix metalloproteinase-2/9 (MMP-2/9) expression and promoted cell apoptosis, but the effect of ATN-161 on proliferation in CNV mice was indirect and required the inhibition of neovascularization. Inhibiting NF-κB activation by ammonium pyrrolidinedithiocarbamate (PDTC) reduced RNV and promoted cell apoptosis in ocular NV. CONCLUSIONS Blocking integrin α5ß1 by ATN-161 reduced ocular NV by inhibiting MMP-2/MMP-9 expression and promoting the cell apoptosis of ocular NV.