Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

A Hybrid Variable Weight Theory Approach of Hierarchical Analysis and Multi-Layer Perceptron for Landslide Susceptibility Evaluation: A Case Study in Luanchuan County, China

Landslides, which can cause significant losses of lives or property damages, result from several different environmental factors whose influences are very complex. Thus, the statistical multi-layer perceptron (MLP) and heuristic analytical hierarchy process (AHP) are employed in the evaluation of landslide susceptibility. However, the landslide susceptibility maps drawn by these two methods are always affected by subjectivity and randomness. In the present study, we introduce variable weight theory (VW) to improve the MLP and AHP methods, and two novel hybrid models, AHP-VW and MLP-VW, are respectively proposed. VW theory is used to redistribute the weights of the factors in the two constant weight evaluations. This is so that the weights of the factors change with different evaluation units, thereby eliminating the subjectivity and randomness problems. The landslide susceptibility maps of the study area were categorized into very low, low, moderate, high, and very high susceptibility grades. The landslide susceptibility maps of the four models are validated by the receiver operating characteristic (ROC) curve. The area under the curve (AUC) is 0.825 for the AHP model, 0.879 for the MLP model, 0.873 for the AHP-VW model, and 0.915 for the MLP-VW model. The results show that the landslide susceptibility map drawn by statistical MLP is better than that drawn by heuristic AHP, which is consistent with many other current research results. Furthermore, VW can significantly improve the performance of constant-weight single models. Landslide susceptibility maps drawn by the statistical MLP model hybrid VW can be used for regional land use planning and landslide hazard mitigation purposes

A Hybrid Variable Weight Theory Approach of Hierarchical Analysis and Multi-Layer Perceptron for Landslide Susceptibility Evaluation: A Case Study in Luanchuan County, China

Landslides, which can cause significant losses of lives or property damages, result from several different environmental factors whose influences are very complex. Thus, the statistical multi-layer perceptron (MLP) and heuristic analytical hierarchy process (AHP) are employed in the evaluation of landslide susceptibility. However, the landslide susceptibility maps drawn by these two methods are always affected by subjectivity and randomness. In the present study, we introduce variable weight theory (VW) to improve the MLP and AHP methods, and two novel hybrid models, AHP-VW and MLP-VW, are respectively proposed. VW theory is used to redistribute the weights of the factors in the two constant weight evaluations. This is so that the weights of the factors change with different evaluation units, thereby eliminating the subjectivity and randomness problems. The landslide susceptibility maps of the study area were categorized into very low, low, moderate, high, and very high susceptibility grades. The landslide susceptibility maps of the four models are validated by the receiver operating characteristic (ROC) curve. The area under the curve (AUC) is 0.825 for the AHP model, 0.879 for the MLP model, 0.873 for the AHP-VW model, and 0.915 for the MLP-VW model. The results show that the landslide susceptibility map drawn by statistical MLP is better than that drawn by heuristic AHP, which is consistent with many other current research results. Furthermore, VW can significantly improve the performance of constant-weight single models. Landslide susceptibility maps drawn by the statistical MLP model hybrid VW can be used for regional land use planning and landslide hazard mitigation purposes

Oxygen isotope composition of meltwater from a Neoproterozoic glaciation in South China

The water cycle is an integral part of Earth surface dynamics, and water\u27s oxygen-isotope composition retains information about the forcing and response of Earth\u27s local and global climate. Water isotope signals of the recent geological past can be directly obtained from archives such as ice cores, groundwater, or pore fluid. For the more distant past, mineral proxies have to be used. Multiple episodes of global glaciation may have occurred in the Neoproterozoic Era, of which the record of oxygen-isotope composition of glacial meltwater is sparse; the few records that are derived from carbonate minerals are prone to late-burial and metamorphic alteration, and therefore subject to alternative explanations. Here we present a case in which meltwater δ18O is retrieved from barite (BaSO4) and malachite (Cu2CO3(OH)2)-associated sulfate (MAS) in a diamictite in Kaiyang, Guizhou, South China. The core of our argument is based on the lowest-ever-published sulfate δ18O values found in the barite and MAS, reaching as low as -20.3‰ (Vienna standard mean ocean water, VSMOW). These data suggest that the water involved in the oxidative weathering of these chalcocite clasts had a δ18O value of -34‰ ± 10‰, similar to that of polar glaciers today. Excluding the possibility of glacier meltwater alteration during the past 600 m.y. after the deposition of the diamictite, the sulfate mineral assemblage reported here provides an important constraint on the nature of the Neoproterozoic glaciation that the Kaiyang diamictite represents. © 2013 Geological Society of America

The Feasibility of Maintaining Biological Phosphorus Removal in A-Stage via the Short Sludge Retention Time Approach: System Performance, Functional Genus Abundance, and Methanogenic Potential

The increasing concerns on resource and energy recovery call for the modification of the current wastewater treatment strategy. This study synthetically evaluates the feasibility of the short sludge retention time approach to improve the energy recovery potential, but keeping steady biological phosphorus removal and system stability simultaneously. SBRS-SRT and SBRcontrol that simulated the short sludge retention time and conventional biological phosphorus removal processes, respectively, were set up to treat real domestic sewage for 120 d. SBRS-SRT achieved an efficient COD (91.5 &plusmn; 3.5%), PO43&minus;-P (95.4 &plusmn; 3.8%), and TP (93.5 &plusmn; 3.7%) removal and maintained the settling volume index around 50 mL/gSS when the sludge retention time was 3 d, indicating steady operational stability. The poor ammonia removal performance (15.7 &plusmn; 7.7%) and a few sequences detected in samples collected in SBRS-SRT indicated the washout of nitrifiers. The dominant phosphorus accumulating organisms Tetrasphaera and Hydrogenophaga, which were enriched with the shortened sludge retention time, was in line with the excellent phosphorus performance of SBRS-SRT. The calculated methanogenic efficiency of SBRS-SRT increased significantly, which was in line with the higher sludge yield. This study proved that the short sludge retention time is a promising and practical approach to integrate biological phosphorus removal in A-stage when re-engineering a biological nutrient removal process

PLA Nanoparticles Loaded With an Active Lactone Form of Hydroxycamptothecin: Development, Optimization, and In Vitro-In Vivo Evaluation in Mice Bearing H22 Solid Tumor

National Key Technology RD Program [2007BAD07B05]; Xiamen Science and Technology Project [3502Z20093009]; Fujian Provincial Health Department [2009-2-79]Hydroxycamptothecin (HCPT)-loaded PLA nanoparticles were prepared by a one-step method using the direct dialysis technique, and were examined for particle characteristics, in vitro drug release, and cytotoxicity, as well as antitumor efficiency. Three main influential factors based on the results of a single-factor test, i.e., PLA concentration, ratio of HCPT to PLA (wt/wt), and dialysis bags with different molecule weight cutoffs, were evaluated using an orthogonal design, giving nanoparticles an average diameter of similar to 226.8nm with smooth surface, modest drug entrapment efficiency (65.15%), and fine drug-oading content (5.16%, w/w). HCPT was in a crystalline state within the particles. In vitro drug release studies exhibited a slow and prolonged release profile over a period of 30 days. The cytotoxicity test on BEL-7402 cells indicated that the HCPT-PLA nanoparticles were more cytotoxic than commercially available HCPT injection. When the antitumor effect was examined by i.v. administration to mice bearing H22 solid tumor, HCPT-PLA nanoparticles showed a significant suppression of tumor growth without loss of body weight. These results suggest that HCPT-PLA nanoparticles prepared by the dialysis technique present desirable characteristics for sustained drug delivery and are potentially useful to enhance the antitumor efficacy of HCPT. Drug Dev Res 72: 337-345, 2011. (C) 2011 Wiley-Liss, Inc

Ginsenoside Rb1 Protects Rat Neural Progenitor Cells against Oxidative Injury

Ginseng, the root of Panax ginseng C.A. Meyer, has been used as a tonic to enhance bodily functions against various ailments for hundreds of years in Far Eastern countries without apparent adverse effects. Ginsenoside Rb1, one of the most active ingredients of ginseng, has been shown to possess various pharmacological activities. Here we report that Rb1 exhibits potent neuroprotective effects against oxidative injury induced by tert-butylhydroperoxide (t-BHP). Lactate dehydrogenase (LDH) assay demonstrated that incubation with 300 µm t-BHP for 2.5 h led to a significant cell loss of cultured rat embryonic cortex-derived neural progenitor cells (NPCs) and the cell viability was pronouncedly increased by 24 h pretreatment of 10 µm Rb1. TUNEL staining further confirmed that pretreatment of Rb1 significantly reduced the cell apoptosis in t-BHP-induced oxidative injury. Real time PCR revealed that pretreatment with Rb1 activated Nrf2 pathway in cultured NPCs and led to an elevated expression of HO-1. The results of the present study demonstrate that Rb1 shows a potent anti-oxidative effect on cultured NPCs by activating Nrf2 pathway