Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury

<p>Abstract</p> <p>Background</p> <p>Stimulation of epithelial sodium channel (ENaC) increases Na⁺transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo.</p> <p>Methods</p> <p>A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting.</p> <p>Results</p> <p>In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway.</p> <p>Conclusions</p> <p>Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.</p

Few-femtosecond Electron Beam with THz-frequency Wakefield-driven Compression

We propose and demonstrate a novel method to produce few-femtosecond electron beam with relatively low timing jitter. In this method a relativistic electron beam is compressed from about 150 fs (rms) to about 7 fs (rms, upper limit) with the wakefield at THz frequency produced by a leading drive beam in a dielectric tube. By imprinting the energy chirp in a passive way, we demonstrate through laser-driven THz streaking technique that no additional timing jitter with respect to an external laser is introduced in this bunch compression process, a prominent advantage over the conventional method using radio-frequency bunchers. We expect that this passive bunching technique may enable new opportunities in many ultrashort-beam based advanced applications such as ultrafast electron diffraction and plasma wakefield acceleration.Comment: 5 pages, 4 figure

Coexistence of aneurysmal subarachnoid hemorrhage and surgically identified pituitary apoplexy: a case report and review of the literature

INTRODUCTION: A ruptured aneurysm associated with a pituitary apoplexy is rare. We present the first case report of the coexistence of a ruptured posterior communicating aneurysm with a surgically discovered pituitary apoplexy where the pituitary apoplexy had not been diagnosed by a pre-operative computerized tomography scan. CASE PRESENTATION: A 31-year-old right-handed Chinese woman began to experience severe headache, vomiting and blurred vision which continued for two days. On admission to the hospital, a brain computerized tomography scan demonstrated a small amount of increased signal in the basal cisterns; no evidence of intrasellar and suprasellar lesions was seen. The appearance of her brain suggested aneurysmal subarachnoid hemorrhage. She had nuchal rigidity and reduced vision. There was no extra-ocular palsy and no other neurological deficit. Our patient had no stigmata of Cushing’s syndrome or acromegaly. During an interview for further history, she reported normal menses and denied reduced vision. Cerebral digital subtraction angiography was subsequently performed, which revealed a 6mm left posterior communicating aneurysm. Urgent left pterional craniotomy was performed. The left ruptured posterior communicating artery aneurysm was completely dissected prior to clipping. At surgery, a suprasellar mass was discovered, the tumor bulging the diaphragma sella and projecting anteriorly under the chiasm raising suspicion of a pituitary tumor. The anterior part of the tumor capsule was opened and a necrotic tumor mixed with dark old blood was removed. The appearance suggested pituitary apoplexy. Histopathology revealed pituitary adenoma with evidence of hemorrhagic necrosis. Our patient made a good recovery. CONCLUSION: Our case report proves that pituitary apoplexy can be coexistent with the rupture of a posterior communicating aneurysm. This association should be considered when evaluating any case of aneurysm. A normal computerized tomography scan does not exclude pituitary apoplexy. Pre-operative magnetic resonance imaging interpretation is required if a pituitary apoplexy is suspected. Craniotomy allows a coexisting aneurysm and pituitary apoplexy to be simultaneously treated

Human Circulating MicroRNA-1 and MicroRNA-126 as Potential Novel Indicators for Acute Myocardial Infarction

Circulating miRNAs have been shown as promising biomarkers for various pathologic conditions. The aim of this study was to clarify that circulating miR-1 and miR-126 in human plasma might be useful as biomarkers in acute myocardial infarction (AMI). In our study, after pre-test, two candidate miRNAs were detected by using real-time RT-PCR. Cardiac troponin I (cTnI) concentrations were measured by ELISA assay in plasma from patients with AMI (n=17) and healthy subjects (n=25), simultaneously. Increased miR-1 and decreased miR-126 in plasma from patients with AMI after the onset of symptoms compared with healthy subjects were found. A remarkable finding in this study is that miR-1, miR-126 and cTnI expression levels exhibited the same trend. Our results suggest that the plasma concentrations of miR-1 and miR-126 may be useful indicators for AMI

Generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation

Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM) crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154, and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants, and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154) were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation will be useful to facilitate the creation of “clean” GM wheat containing only the foreign genes of agronomic importance

Spin-resolved imaging of atomic-scale helimagnetism in monolayer NiI2

Identifying intrinsic noncollinear magnetic order in monolayer van der Waals (vdW) crystals is highly desirable for understanding the delicate magnetic interactions at reduced spatial constraints and miniaturized spintronic applications, but remains elusive in experiments. Here, we achieved spin-resolved imaging of helimagnetism at atomic scale in monolayer NiI2 crystals, that were grown on graphene-covered SiC(0001) substrate, using spin-polarized scanning tunneling microscopy. Our experiments identify the existence of a spin spiral state with canted plane in monolayer NiI2. The spin modulation Q vector of the spin spiral is determined as (0.2203, 0, 0), which is different from its bulk value or its in-plane projection, but agrees well with our first principles calculations. The spin spiral surprisingly indicates collective spin switching behavior under magnetic field, whose origin is ascribed to the incommensurability between the spin spiral and the crystal lattice. Our work unambiguously identifies the helimagnetic state in monolayer NiI2, paving the way for illuminating its expected type-II multiferroic order and developing spintronic devices based on vdW magnets.Comment: 22 pages, 4 figure