A Stochastic Adjustment Strategy for Coordination Process in Distributed Networks

Cloud computing has become a popular basis that integrated into amount of large platforms to support applications (e.g., multimedia, vehicle traffic, and IoT). It is critical to focus on coordinating the part of these applications that execute in the cloud to provide reliable, scalable and available services. Nevertheless, the problem of optimally coordinating the applications is rarely addressed. In this paper, we develop a stochastic model to analyze the fundamental characteristics that occur in ZooKeeper during the coordination process. The model primarily addresses two aspects: demands of followers and the load of a leader. Then, we derive the optimal strategy for provision with deployment of coordinated servers to achieve load balancing based on various factors (e.g. server capacity and network load), so that the overall network performance is optimized. We evaluate our algorithm under realistic settings and reveal the trend of factors such as CPU, memory utilization and network bandwidth with the increasing number of requests. We propose the algorithm that considers how many servers should be deployed and when. Our results demonstrate that the strategy guarantees the performance by making suitable deployment adjustment

Experimental Therapy of Ovarian Cancer with Synthetic Makaluvamine Analog: In Vitro and In Vivo Anticancer Activity and Molecular Mechanisms of Action

The present study was designed to determine the biological effects of novel marine alkaloid analog 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ) on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Human ovarian cancer cells (A2780 and OVCAR-3), and Immortalized non-tumorigenic human Ovarian Surface Epithelial cells (IOSE-144), were exposed to FBA-TPQ for initial cytotoxicity evaluation (via MTS assay kit, Promega). The detailed in-vitro (cell level) and in-vivo (animal model) studies on the antitumor effects and possible underlying mechanisms of action of the compounds were then performed. FBA-TPQ exerted potent cytotoxicity against human ovarian cancer A2780 and OVCAR-3 cells as an effective inhibitor of cell growth and proliferation, while exerting lesser effects on non-tumorigenic IOSE-144 cells. Further study in the more sensitive OVCAR-3 cell line showed that it could potently induce cell apoptosis (Annexin V-FITC assay), G2/M cell cycle arrest (PI staining analysis) and also dose-dependently inhibit OVCAR-3 xenograft tumors' growth on female athymic nude mice (BALB/c, nu/nu). Mechanistic studies (both in vitro and in vivo) revealed that FBA-TPQ might exert its activity through Reactive Oxygen Species (ROS)-associated activation of the death receptor, p53-MDM2, and PI3K-Akt pathways in OVCAR-3 cells, which is in accordance with in vitro microarray (Human genome microarrays, Agilent) data analysis (GEO accession number: GSE25317). In conclusion, FBA-TPQ exhibits significant anticancer activity against ovarian cancer cells, with minimal toxicity to non-tumorigenic human IOSE-144 cells, indicating that it may be a potential therapeutic agent for ovarian cancer

The effects of weight loss and improved metabolic health status on the risk of non-alcoholic fatty liver disease—results from a prospective cohort in China

BackgroundThe impact of weight loss and/or improved metabolic status on the risk of non-alcoholic fatty liver disease (NAFLD) has yet to be determined.MethodsA total of 35,322 participants without NAFLD were followed. NAFLD risk was compared between consistently metabolically healthy non-obese (MHNO) and non-MHNO who lost weight to become non-obese and/or improved their metabolic health, using Cox proportional hazards and logistic regression models.ResultsFollowing 148,186 person-years, 8,409 participants had onset NAFLD, with an incidence rate of 56.75 (95% CI: 55.57, 57.94) per 1,000 person-years. Metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), and metabolically unhealthy non-obese (MUNO) at baseline were associated with increased NAFLD risk, with hazard ratios of 4.48 (95%CI:4.24, 4.73), 8.85 (95%CI:7.95, 9.84), and 10.70 (95%CI:9.73, 11.78). Weight loss and/or metabolic status improvements could significantly reduce NAFLD risk by 79.46 to 41.46%. Specifically, after weight loss from MHO to MHNO, the reduction in NAFLD risk [OR decreased from 12.01 (95%CI:9.40, 15.35) to 4.14 (95%CI:3.08, 5.57)] was greater than that of the MUNO subgroup whose metabolic status improved to MHNO [OR decreased from 5.53 (95%CI:5.15, 5.94) to 2.71 (95%CI:2.50, 3.93)]. In the MUO subgroup, the group with the greatest risk reduction of NAFLD was the weight and metabolic state both improvement group [MUO to MHNO, OR decreased from 22.74 (95%CI:17.61, 29.37) to 4.67 (95%CI:3.05, 7.16)], followed by the weight loss only group [MUO to MUNO, OR decreased to 6.83 (95%CI:4.87, 9.57)], and finally the group with the least and insignificant risk reduction was the metabolic state improvement group [MUO to MHO, OR decreased to 13.38 (95%CI:9.17,19.53)]. NAFLD risk was negatively correlated with the duration of improvement (p < 0.001).ConclusionIndividuals with non-MHNO were more likely to develop NAFLD than those with consistent MHNO, but metabolic improvements and weight loss can alleviate the risk. Their NAFLD risk was negatively correlated with improvement duration. However, it remained higher than in individuals with consistent MHNO at an average follow-up of 4.2 years

Mobile Edge Provision with Flexible Deployment

The Mobile Edge Network (MEN) has emerged as the basic infrastructure to support fifth-generation networks, mobile edge computing and fog computing. The characteristics of mobility must be addressed to guarantee the quality of service in MENs. As one of the critical problems in MENs, flexible deployment plays a part in exploiting edge networks. Despite the abundance of recently proposed strategies, most concentrate on the change in user demands and inevitably ignore the influence for the user mobility, which is common in future networks. We propose Provision for Mobile Edge Computing (PMEC), a prototype that takes advantage of storage devices with flexible placement. In PMEC, we accommodate various considerations and select different storage devices to cache, deploying the cache with the relationship of a two-tiered structure in the MEN. Thus, we construct a flexible overlay network with the objective of minimizing the cost in a two-tiered edge network. Based on the analysis of the problem, we solve the two-tiered placement from bottom to top using the dynamic minimal spanning tree (MST) algorithm and design two algorithms for each tier including the basic algorithm and the improved algorithms. The simulation is conducted on realistic data to demonstrate the performance of our algorithms

Q-FDBA:improving QoE fairness for video streaming.

Multiplayer video streaming scenario can be seen everywhere today as the video traffic is becoming the “killer” traffic over the Internet. The Quality of Experience fairness is critical for not only the users but also the content providers and ISP. Consequently, a QoE fairness adaptive method of multiplayer video streaming is of great importance. Previous studies focus on client-side solutions without network global view or network-assisted solution with extra reaction to client. In this paper, a pure network-based architecture using SDN is designed for monitoring network global performance information. With the flexible programming and network mastery capacity of SDN, we propose an online Q-learning-based dynamic bandwidth allocation algorithm Q-FDBA with the goal of QoE fairness. The results show the Q-FDBA could adaptively react to high frequency of bottleneck bandwidth switches and achieve better QoE fairness within a certain time dimension

Tofacitinib Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Blocking the JAK-STAT1/STAT3 Signaling Pathway

Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan-Janus kinase (JAK) inhibitor that exhibits potent anti-inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide- (LPS-) induced AKI model was established in C57BL/6 mice via an intraperitoneal injection of LPS (10 mg/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15 mg/kg) every 6 h until sacrifice at 24 h. We found that TOFA significantly ameliorated LPS-induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK-STAT1/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS-induced activation of the TLR4/NF-κB pathway. In conclusion, we revealed that TOFA had a protective effect on LPS-induced AKI, and it may be a promising therapeutic agent for septic AKI

RGC-specific ATF4 and/or CHOP deletion rescues glaucomatous neurodegeneration and visual function

Endoplasmic reticulum (ER) stress has been linked with various acute and chronic neurodegenerative diseases. We previously found that optic nerve (ON) injury and diseases induce neuronal ER stress in retinal ganglion cells (RGCs). We further demonstrated that germline deletion of CHOP preserves the structure and function of both RGC somata and axons in mouse glaucoma models. Here we report that RGC-specific deletion of CHOP and/or its upstream regulator ATF4 synergistically promotes RGC and ON survival and preserves visual function in mouse ON crush and silicone oil-induced ocular hypertension (SOHU) glaucoma models. Consistently, topical application of the ATF4/CHOP chemical inhibitor ISRIB or RGC-specific CRISPR-mediated knockdown of the ATF4 downstream effector Gadd45a also delivers significant neuroprotection in the SOHU glaucoma model. These studies suggest that blocking the neuronal intrinsic ATF4/CHOP axis of ER stress is a promising neuroprotection strategy for neurodegeneration

Azithromycin Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells after Stimulation with TNF-α

Background and Objective. This study investigated the effects and underlying mechanisms of azithromycin (AZM) treatment on the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) after their stimulation with TNF-α in vitro. Methods. PDLSCs were isolated from periodontal ligaments from extracted teeth, and MTS assay was used to evaluate whether AZM and TNF-α had toxic effects on PDLSCs viability and proliferation. After stimulating PDLSCs with TNF-α and AZM, we analyzed alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red staining to detect osteogenic differentiation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the mRNA expression of osteogenic-related genes, including RUNX2, OCN, and BSP. Western blotting was used to measure the NF-κB signaling pathway proteins p65, phosphorylated p65, IκB-α, phosphorylated IκB-α, and β-catenin as well as the apoptosis-related proteins caspase-8 and caspase-3. Annexin V assay was used to detect PDLSCs apoptosis. Results. TNF-α stimulation of PDLSCs decreased alkaline phosphatase and alizarin red staining, alkaline phosphatase activity, and mRNA expression of RUNX2, OCN, and BSP in osteogenic-conditioned medium. AZM enhanced the osteogenic differentiation of PDLSCs that were stimulated with TNF-α. Western blot analysis showed that β-catenin, phosphorated p65, and phosphorylated IκB-α protein expression decreased in PDLSCs treated with AZM. In addition, pretreatment of PDLSCs with AZM (10 μg/ml, 20 μg/ml) prevented TNF-α-induced apoptosis by decreasing caspase-8 and caspase-3 expression. Conclusions. Our results showed that AZM promotes PDLSCs osteogenic differentiation in an inflammatory microenvironment by inhibiting the WNT and NF-κB signaling pathways and by suppressing TNF-α-induced apoptosis. This suggests that AZM has potential as a clinical therapeutic for periodontitis

Association of preoperative retinal microcirculation and perioperative outcomes in patients undergoing congenital cardiac surgery

Abstract Background Microcirculatory dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to investigate the association between preoperative retinal microcirculation evaluated using optical coherence tomography angiography (OCTA) and perioperative outcomes in patients with congenital heart disease (CHD). Methods This prospective, observational study was performed from May 2017 to January 2021. OCTA was used to automatically quantify the vessel density (VD) of the superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary (RPC) preoperatively. The primary outcome was excessive postoperative bleeding, defined as bleeding volume > 75th percentile for 24-hour postoperative chest tube output. The secondary outcome was composite adverse outcomes, including one or more operative mortalities, early postoperative complications, and prolonged length of stay. The association between retinal VD and outcomes was assessed using Poisson regression. Results In total, 173 CHD patients who underwent cardiac surgery were included (mean age, 26 years). Among them, 43 (24.9%) and 46 (26.6%) developed excessive postoperative bleeding and composite adverse outcomes, respectively. A lower VD of DCP (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08–1.43; P = 0.003) was independently associated with excessive postoperative bleeding, and a lower VD of RPC (OR, 1.97; 95% CI, 1.08–3.57; P = 0.027), and DCP (OR, 2.17; 95% CI, 1.08–4.37; P = 0.029) were independently associated with the postoperative composite adverse outcomes. Conclusion Preoperative retinal hypoperfusion was independently associated with an increased risk of perioperative adverse outcomes in patients with CHD, suggesting that retinal microcirculation evaluation could provide valuable information about the outcomes of cardiac surgery, thereby aiding physicians in tailoring individualized treatment

Restoration of Foveal Bulge after Resolution of Diabetic Macular Edema with Coexisting Serous Retinal Detachment

Purpose. To evaluate the impact of restoration of foveal bulge (FB) in optical coherence tomography (OCT) images on visual acuity after resolution of diabetic macular edema with coexisting serous retinal detachment (SRD-DME). Methods. A total of 52 eyes with resolved SRD-DME and an intact ellipsoid zone at the central fovea were included. All eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months). The eyes were divided into two groups according to the presence of FB at 6 months. BCVA, central foveal thickness (CFT), height of SRD (SRDH), outer nuclear layer (ONL) thickness, photoreceptor inner segment (PIS), and outer segment (POS) length were compared between the two groups. Results. A FB was found in 25 of 52 (48%) eyes at 6 months. The FB (+) group had lower SRDH at baseline, and better BCVA, longer POS length at 6 months (all P0.05). More eyes in the FB (+) group had complete SRD resolution at 1 month (P=0.009) and 3 months (P=0.012). Eyes with complete SRD resolution at 1 month (P=0.009) or 3 months (P=0.012) were more likely to have a FB at 6 months. Conclusions. The Presence of the FB is associated with better BCVA after resolution of SRD-DME. Eyes with lower baseline SRDH or faster SRD resolution are more likely to have a FB at 6 months