Angiogenesis is a key event in the progression of gliomas, and emerging evidence suggests that exosomes are signaling extracellular organelles that modulate the tumor microenvironment and promote ...angiogenesis and tumor progression. This study aimed to explore the mechanism by which glioma-derived exosomes affect angiogenesis.
qRT-PCR was used to determine the expression level of linc-POU3F3 in glioma tissue as well as glioma cell lines. Ultrafiltration combined with a purification method was used to isolate exosomes derived from A172 cells (A172-Exo) and linc-POU3F3 shRNA-treated A172 cells (shA172-Exo). Transmission electron microscopy, Western blot and tunable resistive pulse sensing (TRPS) were used to identify exosomes. In vitro migration, proliferation, and tube formation experiments, as well as in vivo CAM assays, were used to analyze the pro-angiogenesis ability of exosomes. qRT-PCR and Western blot were used to identify expression levels of angiogenesis-related genes and proteins in human brain microvascular endothelial cells (HBMECs) after being cultured with exosomes.
The levels of linc-POU3F3 were upregulated in glioma tissue and significantly correlated with the advanced tumor stage. A172 cells exhibited the highest expression level. A172-Exo was similar to shA172-Exo (50-100 nm in diameter) and expressed Alix, Tsg101 and CD9, while the expression level of linc-POU3F3 in A172-Exo was significantly higher than that in shA172-Exo. HBMECs rapidly internalized A172-Exo and shA172-Exo, and the linc-POU3F3 expression level in HBMECs treated with A172-Exo was significantly higher than the level in HBMECs treated with shA172-Exo. A172-Exo exhibited better function in promoting HBMECs migration, proliferation, tubular-like structure formation in vitro and arteriole formation in vivo. The gene and protein expression level of bFGF, bFGFR, VEGFA, and Angio in HBMECs treated with A172-Exo was much higher than that of HBMECs treated with shA172-Exo.
These results indicated that gliomas can induce angiogenesis by secreting exosomes enriched in linc-POU3F3. Exosomes and lncRNA-POU3F3 may, therefore, function as a putative therapeutic target in glioma.
To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models.
This retrospective, historical-control study was performed in a cohort of adult cardiac surgical ...patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015-June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality.
Tertiary Zhongshan Hospital (Fudan University, China).
Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery.
Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists.
Successful extubation, ICU LOS and in-hospital mortality.
A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p=0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19h; p<0.001). In relation to patients with MV duration >48h, those in phase II had a comparatively higher successful extubation rate (p=0.033), shorter ICU LOS (p=0.038) and a significant decrease in in-hospital mortality (p=0.039).
The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery.
Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in ...presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.
This research develops a mixed integer linear programming (MILP) model that considers simultaneously both the traditional reservoir rule curves and the hedging rules to manage and operate a ...multipurpose, multireservoir system. During normal periods of operation, when inflows are plentiful, this optimization model efficiently distributes the available stored water from different reservoirs to meet the planned demands imposed by competing users. However, during periods of drought, or when anticipating a drought, the planned demands cannot be fully met, and a water shortage occurs. By considering the hedging rules along with the rule curves, guidelines are provided for reservoir releases. To minimize the impact of drought, the hedging rules effectively reduce the ongoing water supply to balance with the target storage requirement. The MILP model is applied to a multireservoir system in the southern region of Taiwan, where the results obtained demonstrate the applicability and utility of the model.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic ...platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the (1)O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, (1)O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm(-2)) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy.
Modified clay minerals on Mars
Sedimentary rocks exposed in Gale crater on Mars contain extensive clay minerals. Bristow
et al.
analyzed drill samples collected by the Curiosity rover as it climbed ...up sedimentary layers in the crater. They found evidence of past reactions with liquid water and sulfate brines, which could have percolated through the clay from an overlying sulfate deposit. Similar sulfate deposits are widespread across the planet and represent some of the last sedimentary rocks to form before the planet lost its surface liquid water, so the results inform our understanding of the geologic processes that occurred as Mars dried out.
Science, abg5449, this issue p.
198
Clay minerals examined by the Curiosity rover contain evidence of reactions with sulfate brines as Mars dried out.
Mars’ sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The
Curiosity
rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed
Curiosity
to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate–bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.
Summary
Hepatocyte clone size was measured in liver samples of 21 patients in various stages of chronic hepatitis B virus (HBV) infection and from 21 to 76 years of age. Hepatocyte clones containing ...unique virus–cell DNA junctions formed by the integration of HBV DNA were detected using inverse nested PCR. The maximum hepatocyte clone size tended to increase with age, although there was considerable patient‐to‐patient variation in each age group. There was an upward trend in maximum clone size with increasing fibrosis, inflammatory activity and with seroconversion from HBV e‐antigen (HBeAg)‐positive to HBeAg‐negative, but these differences did not reach statistical significance. Maximum hepatocyte clone size did not differ between patients with and without a coexisting hepatocellular carcinoma. Thus, large hepatocyte clones containing integrated HBV DNA were detected during all stages of chronic HBV infection. Using laser microdissection, no significant difference in clone size was observed between foci of HBV surface antigen (HBsAg)‐positive and HBsAg‐negative hepatocytes, suggesting that expression of HBsAg is not a significant factor in clonal expansion. Laser microdissection also revealed that hepatocytes with normal‐appearing histology make up a major fraction of the cells undergoing clonal expansion. Thus, preneoplasia does not appear to be a factor in the clonal expansion detected in our assays. Computer simulations suggest that the large hepatocyte clones are not produced by random hepatocyte turnover but have an as‐yet‐unknown selective advantage that drives increased clonal expansion in the HBV‐infected liver.
During primary infection, murine cytomegalovirus (MCMV) spreads systemically, resulting in virus replication and pathology in multiple organs. This disseminated infection is ultimately controlled, ...but the underlying immune defense mechanisms are unclear. Investigating the role of the cytokine IL-22 in MCMV infection, we discovered an unanticipated function for neutrophils as potent antiviral effector cells that restrict viral replication and associated pathogenesis in peripheral organs. NK-, NKT-, and T cell-secreted IL-22 orchestrated antiviral neutrophil-mediated responses via induction in stromal nonhematopoietic tissue of the neutrophil-recruiting chemokine CXCL1. The antiviral effector properties of infiltrating neutrophils were directly linked to the expression of TNF-related apoptosis-inducing ligand (TRAIL). Our data identify a role for neutrophils in antiviral defense, and establish a functional link between IL-22 and the control of antiviral neutrophil responses that prevents pathogenic herpesvirus infection in peripheral organs.
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•Neutrophils are critical antiviral effector cells during MCMV virus infection•Neutrophils directly inhibit virus replication in a TRAIL-dependent manner•IL-22 inhibits virus replication in peripheral but not secondary lymphoid tissues•IL-22 orchestrates CXCL1-dependent neutrophil recruitment
Murine cytomegalovirus (MCMV) targets multiple peripheral organs during infection. Stacey et al. report that in response to MCMV infection, NK, NKT, and T cells secrete the cytokine IL-22, which recruits antiviral neutrophils to infected peripheral organs in a CXCL1-dependent manner. Neutrophils exert antiviral effector functions via proapoptotic TRAIL expression.
Vera Rubin ridge (VRR) is an erosion-resistant feature on the northwestern slope of Mount Sharp in Gale crater, Mars, and orbital visible/short-wave infrared measurements indicate it contains ...red-colored hematite. The Mars Science Laboratory Curiosity rover performed an extensive campaign on VRR to study its mineralogy, geochemistry, and sedimentology to determine the depositional and diagenetic history of the ridge and constrain the processes by which the hematite could have formed. X-ray diffraction (XRD) data from the CheMin instrument of four samples drilled on and below VRR demonstrate differences in iron, phyllosilicate, and sulfate mineralogy and hematite grain size. Hematite is common across the ridge, and its detection in a gray-colored outcrop suggested localized regions with coarse-grained hematite, which commonly forms from warm fluids. Broad XRD peaks for hematite in one sample below VRR and the abundance of FeOT in the amorphous component suggest the presence of nano-crystalline hematite and amorphous Fe oxides/oxyhydroxides. Well-crystalline akaganeite and jarosite are present in two samples drilled from VRR, indicating at least limited alteration by acid-saline fluids. Collapsed nontronite is present below VRR, but samples from VRR contain phyllosilicate with d(001) = 9.6 Å, possibly from ferripyrophyllite or an acid-altered smectite. The most likely cementing agents creating the ridge are hematite and opaline silica. We hypothesize late diagenesis can explain much of the mineralogical variation on the ridge, where multiple fluid episodes with variable pH, salinity, and temperature altered the rocks, causing the precipitation and crystallization of phases that are not otherwise in equilibrium.
Reservoir operations play an important role in water resources planning and management. During periods of drought, when inflows to the reservoir are low, it may not be possible to satisfy the target ...delivery (planned demand), and shortage occurs. Reservoir hedging rules, which include a set of rule curves and rationing factors, are used to guide the operation under such a situation. In particular, hedging rules are employed to balance the current shortage in supply with future storage to avoid severe water shortages in the future. In general, hedging rules are determined at the planning stage, or at the early stage of a reservoir’s operating life. However, after years of operation, the reservoir system, as well as the demand characteristics, may change. Hence, it becomes necessary to reevaluate and update the existing hedging rules to incorporate changes that have taken place. The purpose of this paper is to devise new hedging rules for an existing multireservoir system. An original mixed-integer nonlinear programming model is transformed to a mixed-integer quadratic programming model. A multireservoir system in southern Taiwan is used as a case study to demonstrate the utility of the model. The results show that the optimized new hedging rules improve the efficiency of reservoir operations of the water distribution system.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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