ORTHRUS: a lightweighted block-level cloud storage system

Taking advantage of distributed storage technology and virtualization technology, cloud storage systems provide virtual machine clients customizable storage service. They can be divided into two types: distributed file system and block level storage system. There are two disadvantages in existing block level storage system: Firstly, Some of them are tightly coupled with their cloud computing environments. As a result, it’s hard to extend them to support other cloud computing platforms; Secondly, The bottleneck of volume server seriously affects the performance and reliability of the whole system. In this paper we present a lightweighted block-level storage system for clouds—ORTHRUS, based on virtualization technology. We first design the architecture with multiple volume servers and its workflows, which can improve system performance and avoid the problem. Secondly, we propose a Listen-Detect-Switch mechanism for ORTHRUS to deal with contingent volume servers’ failure. At last we design a strategy that dynamically balances load between multiple volume servers. We characterize machine capability and load quantity with black box model, and implement the dynamic load balance strategy which is based on genetic algorithm. Extensive experimental results show that the aggregated I/O throughputs of ORTHRUS are significantly improved (approximately two times of that in Orthrus), and both I/O throughputs and IOPS are also remarkably improved (about 1.8 and 1.2 times, respectively) by our dynamic load balance strategy.     

Different ammonia tolerances may facilitate spatial coexistence of Gammarus roeselii and the strong invader Dikerogammarus villosus

The introduction of invasive species that can replace native species is one of the most critical threats to the biodiversity of aquatic systems. Here we investigated the potential contribution of one factor to the coexistence of the indigenous amphipod Gammarus roeselii and the invasive amphipod Dikerogammarus villosus in the same ecosystem (Lake Constance) within different microhabitats. We quantitatively studied the influence of ambient ammonia concentrations on the distributions of the two amphipod species. We also assessed the ammonia tolerance ranges of both species in laboratory experiments by measuring mortality rate, precopula disruption, egg mortality, and microhabitat choice. The proportion of G. roeselii among the two amphipod species was significantly positively related to the ammonia concentration in the water, which indicated that the distribution of the invasive D. villosus was limited at high ammonia concentrations. Although the mortality rates of the two species did not significantly differ, G. roeselii was more tolerant to ammonia with regard to precopula disruption, egg mortality, and microhabitat choice. The effective ammonia concentrations that led to a significantly reduced direct reproductive success in D. villosus were within the range of the highest field concentrations measured, where only G. roeselii occurred. D. villosus may have a smaller range than the indigenous G. roeselii partially because of its lower tolerance to higher ammonia concentrations, which lead to reduced reproductive success. Beside other habitat parameters differences on ammonia tolerance between the two amphipods might allow their coexistence along a gradient of microhabitats in Lake Constance.     

Effects of the Conversion of Native Vegetation to Farmlands on Soil Microarthropod Biodiversity and Ecosystem Functioning in a Desert Oasis

Increased demand for food due to the rapidly growing human population has led to extensive conversion of native steppes at the margins of oases in arid lands of northwest China into intensively managed farmlands. However, the consequences of this land-use change for soil microarthropod biodiversity and ecosystem functioning remain unknown. Here we assessed how conversion of a native steppe to irrigated farmlands of different ages affects the abundance and composition of soil microarthropods and how changes in soil microarthropod biodiversity could scale up to influence soil carbon and nitrogen stocks. We sampled microarthropod communities over two growing seasons from native steppes and cultivated soils of a 27-year-old irrigated farmland and a 90-year-old irrigated farmland, both of which were converted from the native steppe. Topsoil properties and bulk and labile pools of carbon and nitrogen, including soil organic carbon, dissolved organic carbon (DOC), microbial biomass carbon (MBC), total nitrogen (TN), inorganic nitrogen (IN), and microbial biomass nitrogen (MBN), were also measured. The conversion of native steppe to either of the two farmlands significantly increased the abundance and taxa richness of three taxonomic groups (mites, collembolans, and others) and four trophic groups (herbivores, predators, detritivores, and fungivores); this effect was greater in the 90-year-old farmland for the abundance of all taxonomic and trophic groups except for herbivores and was similar between the two farmlands for the richness of all taxonomic and trophic groups. Taxonomic and trophic composition of the microarthropod community showed strong shifts in response to conversion of native steppe to either of the two farmlands. Compositional changes were largely mediated by changes in soil environments. Changes in soil carbon and nitrogen stocks due to conversion of native steppe to farmlands followed similar patterns to soil microarthropod biodiversity, but the greater storage of DOC, MBC, TN, IN, and MBN occurred in the 90-year-old farmland. Our results suggest that soil microarthropod communities are affected positively by native steppe conversion to farmland and farmland age, and that increased microarthropod biodiversity significantly improved the ability of soils to retain carbon and nitrogen.     

Triptolide Induces Growth Inhibition and Apoptosis of Human Laryngocarcinoma Cells by Enhancing p53 Activities and Suppressing E6-Mediated p53 Degradation

Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug.     

Diabetic Patients Could Do As Well as Non-Diabetic Patients without Inflammation on Peritoneal Dialysis

Background

Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.

Methods

Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.

Results

Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.

Conclusion

Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.     

MicroRNA-138 Regulates Hypoxia-Induced Endothelial Cell Dysfunction By Targeting S100A1

The Ca²⁺ sensor S100A1 is essential for proper endothelial cell (EC) nitric oxide (NO) synthase (eNOS) activation. S100A1 levels are greatly reduced in primary human microvascular ECs subjected to hypoxia, rendering them dysfunctional. However mechanisms that regulate S100A1 levels in ECs are unknown. Here we show that ECs transfected with a S100A1–3′ untranslated region (UTR) luciferase reporter construct display significantly reduced gene expression when subjected to low oxygen levels or chemical hypoxia. Bioinformatic analysis suggested that microRNA -138 (MiR-138) could target the 3′UTR of S100A1. Patients with critical limb ischemia (CLI) or mice subjected to femoral artery resection (FAR) displayed increased MiR-138 levels and decreased S100A1 protein expression. Consistent with this finding, hypoxia greatly increased MiR-138 levels in ECs, but not in skeletal muscle C2C12 myoblasts or differentiated myotubes or primary human vascular smooth muscle cells. Transfection of a MiR-138 mimic into ECs reduced S100A1–3 ‘UTR reporter gene expression, while transfection of an anti MiR-138 prevented the hypoxia-induced downregulation of the reporter gene. Deletion of the 22 nucleotide putative MiR-138 target site abolished the hypoxia-induced loss of reporter gene expression. Knockdown of Hif1-α mediated by siRNA prevented loss of hypoxia-induced reporter gene expression. Conversely, specific activation of Hif1-α by a selective prolyl-hydroxylase inhibitor (IOX2) reduced reporter gene expression even in the absence of hypoxia. Finally, primary ECs transfected with a MiR-138 mimic displayed reduced tube formation when plated onto Matrigel matrix and expressed less NO when stimulated with VEGF. These effects were reversed by gene transfer of S100A1 using recombinant adenovirus. We conclude that hypoxia-induced MiR-138 is an essential mediator of EC dysfunction via its ability to target the 3′UTR of S100A1.     

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

Background

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).

Methods

The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.

Principal Findings

Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.

Conclusion

Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”.     

Tumor-Derived Autophagosomes (DRibbles) Induce B Cell Activation in a TLR2-MyD88 Dependent Manner

Previously, we have documented that isolated autophagosomes from tumor cells could efficiently cross-prime tumor-reactive naïve T cells and mediate tumor regression in preclinical mouse models. However, the effect of tumor-derived autophagosomes, here we refer as to DRibbles, on B cells has not been studied so far. At present study, we found that DRibbles generated from a murine hepatoma cell line Hep1-6, induced B-cell activation after intravenous injection into mice. B-cell populations were significantly expanded and the production of Hep1-6 tumor-specific antibodies was successfully induced. Moreover, in vitro studies showed that DRibbles could induce more efficient B-cell proliferation and activation, antibody production, and cytokine secretion than whole tumor cell lysates. Notably, we found that B-cell activation required proteins but not DNA in the DRibbles. We further showed that B cells could capture DRibbles and present antigens in the DRibbles to directly induce T cell activation. Furthermore, we found that B-cell activation, antibody production, cytokine secretion and antigen cross-presentation were TLR2-MyD88 pathway dependent. Taken together, the present studies demonstrated that tumor-derived autophagosomes (DRibbles) efficiently induced B cells activation, antibody production, cytokine secretion and antigen cross-presentation mainly depending on their protein component via TLR2/MyD88 dependent manner.