Rescue of Pressure Overload-Induced Heart Failure by Estrogen Therapy.

BackgroundEstrogen pretreatment has been shown to attenuate the development of heart hypertrophy, but it is not known whether estrogen could also rescue heart failure (HF). Furthermore, the heart has all the machinery to locally biosynthesize estrogen via aromatase, but the role of local cardiac estrogen synthesis in HF has not yet been studied. Here we hypothesized that cardiac estrogen is reduced in HF and examined whether exogenous estrogen therapy can rescue HF.Methods and resultsHF was induced by transaortic constriction in mice, and once mice reached an ejection fraction (EF) of ≈35%, they were treated with estrogen for 10 days. Cardiac structure and function, angiogenesis, and fibrosis were assessed, and estrogen was measured in plasma and in heart. Cardiac estrogen concentrations (6.18±1.12 pg/160 mg heart in HF versus 17.79±1.28 pg/mL in control) and aromatase transcripts (0.19±0.04, normalized to control, P<0.05) were significantly reduced in HF. Estrogen therapy increased cardiac estrogen 3-fold and restored aromatase transcripts. Estrogen also rescued HF by restoring ejection fraction to 53.1±1.3% (P<0.001) and improving cardiac hemodynamics both in male and female mice. Estrogen therapy stimulated angiogenesis as capillary density increased from 0.66±0.07 in HF to 2.83±0.14 (P<0.001, normalized to control) and reversed the fibrotic scarring observed in HF (45.5±2.8% in HF versus 5.3±1.0%, P<0.001). Stimulation of angiogenesis by estrogen seems to be one of the key mechanisms, since in the presence of an angiogenesis inhibitor estrogen failed to rescue HF (ejection fraction=29.3±2.1%, P<0.001 versus E2).ConclusionsEstrogen rescues pre-existing HF by restoring cardiac estrogen and aromatase, stimulating angiogenesis, and suppressing fibrosis

Controllable Entanglement Distribution Network Based on Silicon Quantum Photonics

The entanglement distribution network connects remote users through sharing entanglement resources, which is essential for realizing quantum internet. We proposed a controllable entanglement distribution network (c-EDN) based on a silicon quantum photonic chip. The entanglement resources were generated by a quantum light source array based on spontaneous four-wave mixing (SFWM) in silicon waveguides and distributed to different users through time-reversed Hong-Ou-Mandel interferences in on-chip Mach-Zehnder interferometers with thermal phase shifters. A chip sample was designed and fabricated, supporting a c-EDN with 3 subnets and 24 users. The network topology of entanglement distributions could be reconfigured in three network states by controlling the quantum interferences through the phase shifters, which was demonstrated experimentally. Furthermore, a reconfigurable entanglement-based QKD network was realized as an application of the c-EDN. The reconfigurable network topology makes the c-EDN suitable for future quantum networks requiring complicated network control and management. Moreover, it is also shows that silicon quantum photonic chips have great potential for large-scale c-EDN, thanks to their capacities on generating and manipulating plenty of entanglement resources

Design and Evaluation of Opal2: A Toolkit for Scientific Software as a Service

Abstract—Grid computing provides mechanisms for making large-scale computing environments available to the masses. In recent times, with the advent of Cloud computing, the concepts of Software as a Service (SaaS), where vendors provide key software products as services over the internet that can be accessed by users to perform complex tasks, and Service as Software (SaS), where customizable and repeatable services are packaged as software products that dynamically meet the demands of individual users, have become increasingly popular. Both SaaS and SaS models are highly applicable to scientific software and users alike. Opal2 is a toolkit for wrapping scientific applications as Web services on Grid and cloud computing resources. It provides a mechanism for scientific application developers to expose the functionality of their codes via simple Web service APIs, abstracting out the details of the back-end infrastructure. Services may be combined via cus-tomized workflows for specific research areas and distributed as virtual machine images. In this paper, we describe the overall philosophy and architecture of the Opal2 framework, including its new plug-in architecture and data handling capabilities. We analyze its performance in typical cluster and Grid settings, and in a cloud computing environment within virtual machines

New risk score for predicting progression of membranous nephropathy

Abstract Background Patients with Idiopathic membranous nephropathy (IMN) have various outcomes. The aim of this study is to construct a tool for clinicians to precisely predict outcome of IMN. Methods IMN patients diagnosed by renal biopsy from Shanghai Ruijin Hospital from 2009.01 to 2013.12 were enrolled in this study. Primary outcome was defined as a combination of renal function progression [defined as a reduction of estimated glomerular filtration rate (eGFR) equal to or over 30% comparing to baseline], ESRD or death. Risk models were established by Cox proportional hazard regression analysis and validated by bootstrap resampling analysis. ROC curve was applied to test the performance of risk score. Results Totally 439 patients were recruited in this study. The median follow-up time was 38.73 ± 19.35 months. The enrolled patients were 56 (15–83) years old with a male predominance (sex ratio: male vs female, 1:0.91). The median baseline serum albumin, eGFR-EPI and proteinuria were 23(8–43) g/l, 100.31(12.81–155.98) ml/min/1.73 m2 and 3.98(1.50–22.98) g/24 h, respectively. In total, there were 36 primary outcomes occurred. By Cox regression analysis, the best risk model included age [HR: 1.04(1.003–1.08), 95% CI from bootstrapping: 1.01–1.08), eGFR [HR: 0.97 (0.96–0.99), 95% CI from bootstrapping: 0.96–0.99) and proteinuria [HR: 1.09 (1.01–1.18), 95% CI from bootstrapping: 1.02–1.16). One unit increasing of the risk score based on the best model was associated with 2.57 (1.97–3.36) fold increased risk of combined outcome. The discrimination of this risk score was excellent in predicting combined outcome [C statistics: 0.83, 95% CI 0.76–0.90]. Conclusions Our study indicated that older IMN patients with lower eGFR and heavier proteinuria at the time of renal biopsy were at a higher risk for adverse outcomes. A risk score based on these three variables provides clinicians with an effective tool for risk stratification.https://deepblue.lib.umich.edu/bitstream/2027.42/147736/1/12967_2019_Article_1792.pd

A Rare Genetic Defect of MBL2 Increased the Risk for Progression of IgA Nephropathy

The aim of this study was to investigate the association between lectin pathway-related genetic variations and progression in IgA nephropathy. Biopsy-proven IgAN patients with eGFR ≥15 ml/min/1.73 m2 at baseline and a minimum follow-up of 12-months were enrolled. A total of 1,007 patients and 121 healthy controls were enrolled from two Chinese renal centers. The discovery cohort consisted of 606 patients, and the validation cohort consisted of 401 patients. First, promoters, all exons and their boundary regions of MBL2 and FCN2 were sequenced in 50 patients, and then 37 variations were identified. Of these variations, 7 expression-associated variations were selected and genotyped in the whole discovery cohort. We found that rs1800450 in MBL2 and rs7851696 in FCN2 were associated with an increased risk for ESRD as well as serum MBL or L-ficolin levels. However, only rs1800450 was successively validated for its association with ESRD (HR, 15.91; 3.27–77.34; P = 0.001) in the fully adjusted model in the validation cohort. In addition, 2.7% of patients, and 2.5% of healthy controls carried rs1800450-AA. IgAN patients with rs1800450-AA lacked expression of MBL in both serum and renal tissue and had more severe tubulointerstitial damage. Furthermore, a combined effect of rs1800450-AA with a previously reported clinical risk score was observed in which patients with both a high clinical risk score (≥1%) and rs1800450-AA had a strikingly increased 10-years ESRD risk by 37.1-fold (7.17 to 192.13-fold). In summary, IgAN patients carrying MBL2 rs1800450-AA have a high risk for renal function deterioration, probably due to inactivation of the complement MBL pathway