Smaller Aerobic Granules Significantly Reduce N2O Production by Ammonia-Oxidizing Bacteria: Evidences from Biochemical and Isotopic Analyses.

The mitigation of nitrous oxide (N2O) is of primary significance to offset carbon footprints in aerobic granular sludge (AGS) systems. However, a significant knowledge gap still exists regarding the N2O production mechanism and its pathway contribution. To address this issue, the impact of varying granule sizes, dissolved oxygen (DO), and nitrite (NO2-) levels on N2O production by ammonia-oxidizing bacteria (AOB) during nitrification in AGS systems was comprehensively investigated. Biochemical and isotopic experiments revealed that increasing DO or decreasing NO2- levels reduced N2O emission factors (by 13.8 or 19.5%) and production rates (by 0.08 or 0.35 mg/g VSS/h) via weakening the role of the AOB denitrification pathway since increasing DO competed for more electrons required for AOB denitrification. Smaller granules (0.5 mm) preferred to diminish N2O production via enhancing the role of NH2OH pathway (i.e., 59.4-100% in the absence of NO2-), while larger granules (2.0 mm) induced conspicuously higher N2O production via the AOB denitrification pathway (approximately 100% at higher NO2- levels). Nitrifying AGS systems with a unified size of 0.5 mm achieved 42% N2O footprint reduction compared with the system with mixed sizes (0.5-2.0 mm) under optimal conditions (DO = 3.0 mg-O2/L and NO2- = 0 mg-N/L).

Polyvinyl Chloride Microplastics Facilitate Nitrous Oxide Production in Partial Nitritation Systems.

Partial nitritation (PN) is an important partner with anammox in the sidestream line treating high-strength wastewater and primarily contributes to nitrous oxide (N2O) emissions in such a hybrid system, which also suffers from ubiquitous microplastics because of the growing usage and disposal levels of plastics. In this study, the influences of polyvinyl chloride microplastics (PVC-MPs) on N2O-contributing pathways were experimentally revealed to fill the knowledge gap on N2O emission from the PN system under microplastics stress. The long-term results showed that the overall PN performance was hardly affected by the low-dose PVC-MPs (0.5 mg/L) while obviously deteriorated by the high dose (5 mg/L). According to the batch tests, PVC-MPs reduced biomass-specific ammonia oxidation rates (AORs) by 5.78-21.94% and stimulated aerobic N2O production by 9.22-88.36%. Further, upon increasing dissolved oxygen concentrations from 0.3 to 0.9 mg O2/L, the degree of AOR inhibition increased but that of N2O stimulation was lightened. Site preference analysis in combination with metabolic inhibitors demonstrated that the contributions of hydroxylamine oxidation and heterotrophic denitrification to N2O production at 0.3 mg O2/L were enhanced by 18.84 and 10.34%, respectively, accompanied by a corresponding decreased contribution of nitrifier denitrification. Finally, the underlying mechanisms proposed for negative influences of PVC-MPs were bisphenol A leaching and reactive oxygen species production, which led to more cell death, altered sludge properties, and reshaped microbial communities, further resulting in enhanced N2O emission. Overall, this work implied that the ubiquitous microplastics are a hidden danger that cannot be ignored in the PN system.

Decreased plasma exposure of clopidogrel active metabolite in rats after long-term treatment with clopidogrel.

Clopidogrel (Clop) is oxidized by cytochrome P450s (CYPs) to an active thiol metabolite, Clop-AM, to inhibit platelet activation and aggregation. As an irreversible inhibitor of CYP2B6 and CYP2C19, clopidogrel may inhibit its own metabolism after long-term administration. The study compared the pharmacokinetic profiles of clopidogrel and its metabolites in rats receiving a single or a 2 week administration of Clop. The mRNA and protein levels of hepatic clopidogrel-metabolizing enzymes and their enzymatic activities were analyzed to explore their contribution to any altered plasma exposure of Clop and its metabolites. The results showed that long-term treatment with clopidogrel significantly decreased the AUC(0-t) and Cmax values of Clop-AM in rats, accompanied with markedly impaired catalytic activities of Clop-metabolizing CYPs including CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4. It suggests that consecutive administration of Clop to rats decreases hepatic CYPs activities, which may, in turn, inhibit clopidogrel metabolism and then reduce Clop-AM plasma exposure. Therefore, long-term treatment with clopidogrel has the potential to reduce its anti-platelet activity and to increase the risk of drug-drug interaction.

Antibiotics-induced disruption of gut microbiota increases systemic exposure of clopidogrel active metabolite in type 2 diabetic rats.

Gut microbiota play an important role in the pathophysiology of type 2 diabetic mellitus (T2DM) and biodisposition of drugs. Our previous study demonstrated that T2DM rats had the decreased plasma exposure of clopidogrel active metabolite (Clop-AM) due to upregulation of P-glycoprotein (P-gp). However, whether the change to clopidogrel (Clop) disposition under T2DM condition is associated with gut microbiota needs to be elucidated. In the study, we used an antibiotic cocktail consisting of ampicillin, vancomycin, metronidazole, and neomycin to disrupt gut microbiota and observed their influence on pharmacokinetic profiles of Clop-AM. Antibiotic administration markedly alleviated T2DM rats' phenotype including hyperglycemia, insulin resistance, oxidative stress, inflammation, hyperlipidemia, and liver dysfunction. Meanwhile, treatment with antibiotics significantly reversed the reduced systemic exposure of Clop-AM in T2DM rats relative to control rats, which was associated with the decreased intestinal P-gp level that might promote Clop absorption, resulting in more Clop transformation to Clop-AM. Fecal microbiome analysis exhibited a serious disruption of gut microbiota after antibiotic treatment with the sharply reduced microbial load and the altered microbial composition. Interestingly, an in vitro study showed that antibiotics had no influence on P-gp mRNA leve in SW480 cells, suggesting the microbiome disruption, not the direct role of antibiotics on P-gp expression, contributes to the altered P-gp level and Clop disposition in T2DM rats. The findings add new insights into the potential impact of gut microbiota on Clop biodisposition. Significance Statement 1.Antibiotics increase systemic exposure of Clop-AM in T2DM rats, which is associated with the downregulation of P-gp level.2.Antibiotics-induced disruption of gut microbiota, not direct effect of antibiotics on P-gp and CYPs expression, contributes to the altered Clop disposition.3.Antibiotics also alleviate T2DM phenotype including hyperglycemia, hyperlipidemia, insulin resistance, liver dysfunction and inflammation.

Minimal effect of conditional ferroportin KO in the neural retina implicates ferrous iron in retinal iron overload and degeneration.

Iron-induced oxidative stress can cause or exacerbate retinal degenerative diseases. Retinal iron overload has been reported in several mouse disease models with systemic or neural retina-specific knockout (KO) of homologous ferroxidases ceruloplasmin (Cp) and hephaestin (Heph). Cp and Heph can potentiate ferroportin (Fpn) mediated cellular iron export. Here, we used retina-specific Fpn KO mice to test the hypothesis that retinal iron overload in Cp/Heph DKO mice is caused by impaired iron export from neurons and glia. Surprisingly, there was no indication of retinal iron overload in retina-specific Fpn KO mice: the mRNA levels of transferrin receptor in the retina were not altered at 7-10-months age. Consistent with this, levels and localization of ferritin light chain were unchanged. To "stress the system", we injected iron intraperitoneally into Fpn KO mice with or without Cp KO. Only mice with both retina-specific Fpn KO and Cp KO had modestly elevated retinal iron levels. These results suggest that impaired iron export through Fpn is not sufficient to explain the retinal iron overload in Cp/Heph DKO mice. An increase in the levels of retinal ferrous iron caused by the absence of these ferroxidases, followed by uptake into cells by ferrous iron importers, is most likely necessary.

Association Between Cardiovascular Health and Retinopathy in US Adults: From NHANES 2005-2008.

PURPOSE: Investigating the relationship between cardiovascular health (CVH) and retinopathy in the adult population of the United States. DESIGN: The cross-sectional study. METHODS: The study utilized samples, including the diabetes population, from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008 (N= 4249), to assess cardiovascular health (CVH) using the Life's Essential 8 (LE8) assessment. Retinopathy is determined through imaging assessment by professionals independently grading fundus photographs. Univariable and multivariable weighted logistic regression models, restricted cubic splines (RCS), subgroup analysis and weighted quantile sum (WQS) regression approaches were employed to assess the association between LE8 score-based CVH status and retinopathy. The mediation analysis was conducted to investigate whether serum albumin levels mediated the relationship between LE8 score and retinopathy. RESULTS: In a fully adjusted logistic regression model, participants in the moderate and high CVH groups had a 39% (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.43-0.87, P-value = 0.01) and 56% (OR 0.44, 95% CI 0.25-0.77, P-value < 0.001) lower odds of developing retinopathy compared to the low CVH group. The RCS model indicates a significant non-linear relationship between CVH and retinopathy. The WQS regression analysis suggests that blood glucose (47.65%) and blood pressure (19.41%) have the highest weights in relation to retinopathy. Mediation analysis suggests that serum albumin partially mediates the relationship between LE8 scores and retinopathy. CONCLUSION: This study demonstrates a significant negative correlation between overall cardiovascular health measured by LE8 scores and retinopathy. Public health strategies that promote achieving optimal cardiovascular health indicators may help reduce the burden of retinal microvascular diseases.

Biodegradable microplastics aggravate greenhouse gas emissions from urban lake sediments more severely than conventional microplastics.

Freshwater ecosystems, such as urban lake sediments, have been identified as important sources of greenhouse gases (GHGs) to the atmosphere, as well as persistent sinks for ubiquitous microplastics due to the high population density and frequent anthropogenic activity. The potential impacts of microplastics on GHG production, however, remain underexplored. In this study, four types of common biodegradable microplastics (BMPs) versus four conventional non-biodegradable microplastics (NBMPs) were artificially exposed to urban lake sediments to investigate the responses of nitrous oxide (N2O) and methane (CH4) production, and make a comparison regarding how the biodegradability of microplastics affected GHG emissions. Importantly, results suggested that BMPs aggravated N2O and CH4 production in urban lake sediments more severely than conventional NBMPs. The production rates of N2O and CH4 increased by 48.78-71.88 % and 30.87-69.12 %, respectively, in BMPs groups, while those increased by only 0-25.69 % and 6.46-10.46 % with NBMPs exposure. Moreover, BMPs insignificantly affected nitrification but facilitated denitrification, while NBMPs inhibited both processes. BMPs not only created more oxygen-limited microenvironment, greatly promoting N2O production via nitrifier denitrification pathway, but also provided dissolved organic carbon favoring heterotrophic denitrification, which was primarily supported by the enriched denitrifiers and functional genes. In contrast, NBMPs slightly upregulated nitrifier denitrification pathway to generate N2O, and showed a toxic inhibition on both nitrifiers and denitrifiers. In addition, both BMPs and NBMPs promoted hydrogen-dependent methanogenic pathway but suppressed acetate-dependent pathway. The greater enhancement of CH4 production with BMPs exposure was attributed to the additional organic carbon substrates derived from BMPs and the stimulated microbial methane metabolism activities.

Evaluation of nitrogen removal and nitrous oxide turnovers in granule-based simultaneous nitrification and denitrification system.

Nitrous oxide (N2O) is an inevitable intermediate generated during the nitrogen removal process of granule-based simultaneous nitrification and denitrification (SND) system. In order to alleviate N2O production while maintaining a desired total nitrogen (TN) removal level in this system, a comprehensive evaluation of the contribution pathways and process parameters affecting N2O turnovers is keenly required. Therefore, mathematical models were applied to evaluate the impact of operating conditions and unravel potential mechanisms on TN removal performance and N2O production. Simulation results show that higher N2O production (11.6 %-14.2 %) occurs at higher dissolved oxygen (DO) concentrations, lower chemical oxygen demand (COD) levels, longer hydraulic retention time (HRT) and larger granule size in the granular SND system. The relative conversion rates of nitrogenous components in different regions within the granule influence N2O turnovers, with the nitrification process occurring only in the region 200 µm inward from the granule surface and denitrification working throughout the entire granule. In the inner region of the granule (0-300 µm), the heterotrophic bacteria (HB) denitrification pathway dominates N2O production as a source of N2O. While in the outer region (300-450 µm), HB denitrification acts as a sink for N2O and regulates N2O turnovers (i.e. production and reduction of N2O) together with the hydroxylamine (NH2OH) pathway that is the main contributor of N2O production. Moreover, simultaneous adjustment of multiple operating parameters within a certain range can lower the N2O production factor (<0.5 %) while achieving the desired TN removal efficiency (>80 %), resulting in a feasible N2O mitigation strategy.

Unveiling the roles of biofilm in reducing N2O emission in a nitrifying integrated fixed-film activated sludge (IFAS) system.

Biofilm process such as integrated fixed-film activated sludge (IFAS) system has been preliminarily found to produce less nitrous oxide (N2O) than suspended sludge system. However, the N2O emission behaviors and underlying N2O mitigation mechanism in such hybrid system remain unclear. This study therefore aims to fully unveil the roles of biofilm in reducing N2O emission in a nitrifying IFAS system with the aid of some advanced technologies such as N2O microsensor and site-preference analysis. It was found that ammonia oxidation occurred mostly in the sludge flocs (˃ 86%) and biofilm could reduce N2O emission by 43.77% in a typical operating cycle. Biofilm not only reduced nitrite accumulation in nitrification process, inhibiting N2O production via nitrifier denitrification pathway, but also served as a N2O sink, promoting the reduction of N2O via endogenous denitrification. As a result, N2O emissions from the IFAS system were 50%-83% lower than those from the solo sludge flocs. Further, more N2O emission was reduced in the presence of biofilm with decreasing the dissolved oxygen level in the range of 0.5-3.0 mg O2/L. Microbial community and key enzyme analyses revealed that biofilm had relatively high microbial diversity and unique enzyme composition, providing a reasonable explanation for the changed contributions of different N2O production pathways and reduced N2O emission.

The effect of organic sources on the electron distribution and N2O emission in sulfur-driven autotrophic denitrification biofilters.

Sulfur-driven autotrophic denitrification (SAD) is considered as an effective alternative to traditional heterotrophic denitrification (HD) due to its cheap, low sludge production and non-toxicity. Nitrous oxide (N2O) as an intermediate product inevitably was generated at the limited supply of electron donor or unbalanced electron distribution condition during the denitrification process. Recently, autotrophic denitrification biofilters were conclusively implemented for advanced nitrogen removal in wastewater treatment plant (WWTP). However, residual organic sources after wastewater treatment could affect the electron distribution among denitrifying reductases and few studies are known about this issue. In this study, several lab-scale biofilters packed with elemental sulfur slices were applied to explore the electron distribution characteristics of autotrophic denitrification through the combination of different nitrogen oxides (NOx). The results clearly delineated that the different combination of nitrogen oxides had a remarkable effect on the electron distribution. In any case, the electrons likely flow toward nitrate reductase (Nar) under a single nitrogen oxide combination, followed by nitrite reductase (Nir) and nitrous oxide reductase (Nos). The concurrent presence of multiple electron acceptors resulted in most electrons flowing toward Nar, and least toward Nos. Compared to traditional SAD, the reduction rate of nitrogen oxide in the sulfur-driven autotrophic denitrification with influent of organic source (OSAD) was greatly improved. The maximum value of the true specific rates of NO3- in OSAD process was 9.43 mg-N/g-VSS/h. It was increased by 8.26 folds higher than that in traditional SAD. The electrons were more easily distributed to Nos with the addition of sodium acetate, which further promoted the N2O reduction. This study will provide theoretical support for controlling N2O release in SAD biofilters.

Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.

Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1). In a liver-specific Hepc (Hamp) knockout murine model of systemic iron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes and ceramides. The proteolytic enzyme cathepsin D (CTSD) had impaired maturation. A large proportion of lysosomes were galectin-3 (Lgals3) positive, suggesting cytotoxic lysosomal membrane permeabilization. Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.

Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells.

A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Preliminary research on the mechanism of action showed that the inhibition might perform through combination of apoptosis, autophagy and cell cycle arrest.

Light-introduced partial nitrification in an algal-bacterial granular sludge bioreactor: Performance evolution and microbial community shift.

This objective of study was to evaluate the influence of light on the achievement of partial nitrification algal-bacterial granular bioreactor and its related nitrite accumulation mechanism. After 150-days operation, partial nitrification algal-bacterial granulation bioreactor was achieved under the 200 µmol/(m2·s) illuminance condition. The effluent NH4+-N, NO2--N, NO3--N concentrations were average at 1.1, 61.7 and 8.0 mg/L (n = 21), respectively. The average sphericity of algal-bacterial aerobic granular sludge (AB-AGS) increased from 82.7% to 91.1%, accompanied by the significantly increased diameter. Additionally, extracellular protein increased by 1.5 times and 0.5 times higher in LB-EPS and TB-EPS of AB-AGS, respectively. According to typical cycles, N2O emission amount reactor accounted for 2.4% of the removed nitrogen. Under the combined inhibition of light and free ammonia (FA), Nitrosomonas-related AOB (0.2% to 2.1%) were the predominant functional bacteria, whereas Nitrospira-related NOB (0.07% to below 0.01%) was fully inhibited.

Insights into N2O turnovers under polyethylene terephthalate microplastics stress in mainstream biological nitrogen removal process.

The ubiquitous microplastics in wastewater have raised growing concerns due to their unintended effects on microbial activities. However, whether and how microplastics affect nitrous oxide (N2O) (a potent greenhouse gas) turnovers in mainstream biological nitrogen removal (BNR) process remain unclear. This work therefore aimed to fill such knowledge gap by conducting both long-term and batch tests. After over 100 days of feeding with wastewater containing polyethylene terephthalate (PET) microplastics (0-500 µg/L), the long-term results showed that both production and reduction of N2O during denitrification were reduced, as well as the N2O production during nitrification. Accordingly, 60% reduction in N2O accumulation and 70% reduction in N2O production were observed in the denitrification and nitrification batch tests, respectively. Nevertheless, the long-term N2O emission factors under PET microplastics stress were comparable to that in the control reactor, mainly because PET microplastics led to more nitrite accumulation in anoxic period. With the aid of online N2O sensors and site-preference analysis, it was demonstrated that the heterotrophic bacteria pathway and ammonia oxidizing bacteria denitrification pathway for N2O production were negatively affected by PET microplastics, whereas a clear increase in the contribution of hydroxylamine pathway (+ 22.9%) was observed. Further investigation revealed that PET microplastics even at environmental level (i.e. 10 µg/L) significantly reshaped the BNR sludge characteristics (e.g. much larger particle size) and microbial communities (e.g. Thauera, Rhodobacte and Nitrospira) as well as the nitrogen metabolism pathways, which were chiefly responsible for the changes of N2O turnovers and N2O production pathways under the PET microplastics stress.

Contribution of nitrification and denitrification to nitrous oxide turnovers in membrane-aerated biofilm reactors (MABR): A model-based evaluation.

As a novel and sustainable technology, membrane-aerated biofilm reactors (MABR) performing simultaneous nitrification and denitrification face the challenge of undesirable nitrous oxide (N2O) emission. Thereby, a comprehensive analysis of N2O turnover pathways and the affecting parameters in MABR are demanded for N2O mitigation strategies. In this work, a mathematical model describing three N2O turnovers pathways was studied to uncover the underlying mechanisms and the impacts of operational conditions on N2O turnovers in MABR system performing simultaneous nitrification and denitrification. The modeling results demonstrate that higher oxygen surface loading, longer hydraulic retention time (HRT) and lower influent chemical oxygen demand (COD) significantly induce higher N2O production factor (0.18%-3.3%). N2O turnovers are mainly regulated by the hydroxylamine (NH2OH) pathway and heterotrophic bacteria (HB) denitrification, accounting for 76%-87% and 10%-21%, respectively. In contrast, the thicker biofilm (i.e., 400-600 µm) causes lower N2O production factor (<0.13%), due to the shift of N2O turnover pathways to the ammonium oxidizing bacteria (AOB) denitrification pathway (7.1%-9.3%) and HB denitrification (90.7%-92.9%). Meanwhile, the result of in-biofilm N2O conversion rates shows that the NH2OH pathway and HB denitrification become the predominant N2O production pathway at the inner zone (0-160 µm) and the outer zone (290-350 µm) of the biofilm in MABR, respectively. The biofilm thickness at 160-280 µm can thus be regarded as an optimal zone to reduce N2O production in MABR, due to more electrons preferentially used for N2O reduction. The relatively low N2O production factor (<0.5%) together with >80% total nitrogen (TN) removal in MABR can be achieved by controlling the oxygen surface loading (1.821-3.641 g/m2/d) and influent COD concentrations (285-500 mg/L) within a certain range.

Deuterated docosahexaenoic acid protects against oxidative stress and geographic atrophy-like retinal degeneration in a mouse model with iron overload.

Oxidative stress plays a central role in age-related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes. Oxidation of DHA produces toxic oxidation products including carboxyethylpyrrole (CEP) adducts, which are increased in the retinas of AMD patients. In this study, we hypothesized that deuterium substitution on the bis-allylic sites of DHA in photoreceptor membranes could prevent iron-induced retinal degeneration by inhibiting oxidative stress and lipid peroxidation. Mice were fed with either DHA deuterated at the oxidation-prone positions (D-DHA) or control natural DHA and then given an intravitreal injection of iron or control saline. Orally administered D-DHA caused a dose-dependent increase in D-DHA levels in the neural retina and retinal pigment epithelium (RPE) as measured by mass spectrometry. At 1 week after iron injection, D-DHA provided nearly complete protection against iron-induced retinal autofluorescence and retinal degeneration, as determined by in vivo imaging, electroretinography, and histology. Iron injection resulted in carboxyethylpyrrole conjugate immunoreactivity in photoreceptors and RPE in mice fed with natural DHA but not D-DHA. Quantitative PCR results were consistent with iron-induced oxidative stress, inflammation, and retinal cell death in mice fed with natural DHA but not D-DHA. Taken together, our findings suggest that DHA oxidation is central to the pathogenesis of iron-induced retinal degeneration. They also provide preclinical evidence that dosing with D-DHA could be a viable therapeutic strategy for retinal diseases involving oxidative stress.

Molecular mechanisms of metal ions in regulating the catalytic efficiency of D-psicose 3-epimerase revealed by multiple short molecular dynamic simulations and free energy predictions.

Communicated by Ramaswamy H. Sarma.

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia.

Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.

Synthesis of novel oxime-containing pyrazole derivatives and discovery of regulators for apoptosis and autophagy in A549 lung cancer cells.

A series of novel oxime-containing pyrazole derivatives were synthesized by the reaction of ethyl 3-phenyl-1H-pyrazole-5-carboxylate derivatives and 2-bromo-1-phenylethanone followed by the reaction with hydroxylamine hydrochloride. The structures were determined by IR, (1)H NMR, HRMS, and X-ray analysis. A dose- and time-dependent inhibition of proliferation was observed in A549 lung cancer cell after compound treatment. Inhibition of growth was mainly attributed to the autophagy induction.

GO/PEDOT:NaPSS modified cathode as heterogeneous electro-Fenton pretreatment and subsequently aerobic granular sludge biological degradation for dye wastewater treatment.

Heterogeneous electro-Fenton (EF) technology has been wildly applied for the treatment of wastewater containing dyes and other organic pollutants. However, biologically treatment should be further applied after heterogeneous electro-Fenton process in order get better effluent quality. In the present study, a simple electropolymerization method using poly (3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) was applied for graphite felt (GF) electrode modification as cathode in EF system, and coupling subsequently aerobic granular sludge (AGS) biological treatment for dye wastewater treatment. The modified electrode was characterized by scanning electron microscopy (SEM), Raman spectrum, and cyclic voltammetry (CV). Data implied that much higher H2O2 productivity, current response and coulomb efficiency (CE) were achieved by using GO/PEDOT:NaPSS modified GF. The results could be ascribed to the synergistic effect between PEDOT and GO that accelerated the electron transfer rate. Moreover, the H2O2 production capacity remained over 84.2% after 10-times reuses for GO/PEDOT:NaPSS modified GF, indicating that GO significantly improved the stability and life of electrode. Compared with the single system, the total organic carbon (TOC) and chemical oxygen demand (COD) removal efficiencies of the combined system degradation methylene blue (MB) wastewater were significantly improved. Therefore, this modified GF could be used as a potentially useful cathode in heterogeneous EF technology for actual wastewater treatment and the combined system have a promising engineering application value in MB wastewater degradation field.