Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.

[1] We measured Vp/Vs ratios of thermally cracked Westerly granite, thermally cracked Carrara marble and 4% porosity Fontainebleau sandstone, for an effective mean pressure ranging from 2 to 95 MPa. Samples were fluidsaturated alternatively with argon gas and water (5 MPa constant pore pressure). The experimental results show that at ultrasonic frequencies, Vp/Vs ratio of water saturated specimen never exceeded 2.15, even at effective mean pressure as low as 2 MPa, or for a lithology for which the Poisson's ratio of minerals is as high as 0.3 (calcite). In order to check these results against theoretical models: we examine first a randomly oriented cracked medium (with dispersion but without anisotropy); and second a medium with horizontally aligned cracks (with anisotropy but without dispersion). The numerical results show that experimental data agree well with the first model: at high frequency, Vp/Vs ratios range from 1.6 to 1.8 in the dry case and from 1.6 to 2.2 in the saturated case. The second model predicts both Vp/Sv and Vp/Sh to vary from 1.2 to 3.5, depending on the raypath angle relative to the crack fabric. In addition, perpendicular to the crack fabric, a high Vp/Vs ratio is predicted in the absence of shear wave splitting. From these results, we argue the possibility that high Vp/Vs ratio (>2.2) as recently imaged by seismic tomography in subduction zones, may come from zones presenting important crack anisotropy. The cumulative effects of crack anisotropy and high pore fluid pressure are required to get Vp/Vs ratios above 2.2. Citation:

Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4+Foxp3+ regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4+CD25− T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-β by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.

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Global warming is changing the hydrological cycle in multiple ways such as increased cloudiness, latent heat fluxes, and intense precipitation events. How extreme rainfall events will be influenced by the changing climate is becoming one of the most important problems for hydrological risk analysis and engineering design. In this study, a regional climate modeling approach based on the Providing REgional Climates for Impacts Studies modeling system is proposed for investigating the potential impacts of climate change induced by increased greenhouse gases on the intensity and frequency of extreme rainfall events in the context of Ontario, Canada. An ensemble of high-resolution climate projections is first developed under both current and future forcing conditions. Validation of the ensemble simulations is then conducted through comparing the simulated rainfall annual extremes for 1960-1990 to the observed ones. Following that, the rainfall projections for future periods are used to develop projected intensity-duration-frequency curves and their plausible changes in 2030s, 2050s, and 2080s for the City of Toronto. The results suggest that intensities of rainfall extreme events versus various durations with different return periods are all likely to increase over time: [5, 17]% in 2030s, [11, 22]% in 2050s, and [25, 50]% in 2080s. Such a consistent increase would lead to an overall uplift in the exceedance values of rainfall intensity of extreme events, implying that intense rainfall events are likely to occur more frequently in the future. In addition, more significant changes in the rainfall intensity are projected for extreme events with longer return periods at all given durations.