Allenpetterson1516

Uremic vascular calcification (VC) commonly occurs during advanced chronic kidney disease (CKD) and significantly increases cardiovascular morbidity and mortality. Uremic toxins are integral within VC pathogenesis, as they exhibit adverse vascular influences ranging from atherosclerosis, vascular inflammation, to VC. Experimental removal of these toxins, including small molecular (phosphate, trimethylamine-N-oxide), large molecular (fibroblast growth factor-23, cytokines), and protein-bound ones (indoxyl sulfate, p-cresyl sulfate), ameliorates VC. As most uremic toxins share a gut origin, interventions through gastrointestinal tract are expected to demonstrate particular efficacy. The "gastrointestinal decontamination" through the removal of toxin in situ or impediment of toxin absorption within the gastrointestinal tract is a practical and potential strategy to reduce uremic toxins. First and foremost, the modulation of gut microbiota through optimizing dietary composition, the use of prebiotics or probiotics, can be implemented. Other promising strategies such as reducing calcium load, minimizing intestinal phosphate absorption through the optimization of phosphate binders and the inhibition of gut luminal phosphate transporters, the administration of magnesium, and the use of oral toxin adsorbent for protein-bound uremic toxins may potentially counteract uremic VC. Novel agents such as tenapanor have been actively tested in clinical trials for their potential vascular benefits. find more Further advanced studies are still warranted to validate the beneficial effects of gastrointestinal decontamination in the retardation and treatment of uremic VC.Flaviviruses bear class II fusion proteins as their envelope (E) proteins. Here, we describe the development of an in vitro quantitative mosquito-cell-based membrane-fusion assay for the E protein using dual split proteins (DSPs). The assay does not involve the use of live viruses and allows the analysis of a membrane-fusion step independent of other events in the viral lifecycle, such as endocytosis. The progress of membrane fusion can be monitored continuously by measuring the activities of Renilla luciferase derived from the reassociation of DSPs during cell fusion. We optimized the assay to screen an FDA-approved drug library for a potential membrane fusion inhibitor using the E protein of Zika virus. Screening results identified atovaquone, which was previously described as an antimalarial agent. Atovaquone potently blocked the in vitro Zika virus infection of mammalian cells with an IC90 of 2.1 µM. Furthermore, four distinct serotypes of dengue virus were also inhibited by atovaquone with IC90 values of 1.6-2.5 µM, which is a range below the average blood concentration of atovaquone after its oral administration in humans. These findings make atovaquone a likely candidate drug to treat illnesses caused by Zika as well as dengue viruses. Additionally, the DSP assay is useful to study the mechanism of membrane fusion in Flaviviruses.Peptide aptamers are short amino acid chains that are capable of binding specifically to ligands in the same way as their much larger counterparts, antibodies. Ligands of therapeutic interest that can be targeted are other peptide chains or loops located on the surface of protein receptors (e.g., GCPR), which take part in cell-to-cell communications either directly or via the intermediary of hormones or signalling molecules. To confer on aptamers the same sort of conformational rigidity that characterises an antibody binding site, aptamers are often constructed in the form of cyclic peptides, on the assumption that this will encourage stronger binding interactions than would occur if the aptamers were simply linear chains. However, no formal studies have been conducted to confirm the hypothesis that linear peptides will engage in stronger binding interactions with cyclic peptides than with other linear peptides. In this study, the interaction of a model cyclic decamer with a series of linear peptide constructs was compared with that of a linear peptide with the same sequence, showing that the cyclic configuration does confer benefits by increasing the strength of binding.Silicon-based light emitting diodes (LED) are indispensable elements for the rapidly growing field of silicon compatible photonic integration platforms. In the present study, graphene has been utilized as an interfacial layer to realize a unique illumination mechanism for the silicon-based LEDs. We designed a Si/thick dielectric layer/graphene/AlGaN heterostructured LED via the van der Waals integration method. In forward bias, the Si/thick dielectric (HfO2-50 nm or SiO2-90 nm) heterostructure accumulates numerous hot electrons at the interface. At sufficient operational voltages, the hot electrons from the interface of the Si/dielectric can cross the thick dielectric barrier via the electron-impact ionization mechanism, which results in the emission of more electrons that can be injected into graphene. The injected hot electrons in graphene can ignite the multiplication exciton effect, and the created electrons can transfer into p-type AlGaN and recombine with holes resulting a broadband yellow-color electroluminescence (EL) with a center peak at 580 nm. In comparison, the n-Si/thick dielectric/p-AlGaN LED without graphene result in a negligible blue color EL at 430 nm in forward bias. This work demonstrates the key role of graphene as a hot electron active layer that enables the intense EL from silicon-based compound semiconductor LEDs. Such a simple LED structure may find applications in silicon compatible electronics and optoelectronics.We investigated prognostic factors associated with refractory left ventricle (LV) failure leading to LV assist device (LVAD), heart transplant or death in patients on an axial flow pump support for cardiogenic shock (CS). Sixty-two CS patients with an Impella® CP or 5.0 implant were retrospectively enrolled, and clinical, biological, echocardiographic, coronarographic and management data were collected. They were compared according to the 30-day outcome. Patients were mainly male (n = 55, 89%), 58 ± 11 years old and most had no history of heart failure or coronary artery disease (70%). The main etiology of CS was acute coronary syndrome (n = 57, 92%). They presented with severe LV failure (LV ejection fraction (LVEF) 22 ± 9%), organ malperfusion (lactate 3.1 ± 2.1 mmol/L), and frequent use of inotropes, vasopressors, and mechanical ventilation (59, 66 and 30%, respectively). At 24 h, non-recovery was associated with higher total bilirubin (odds ratios (OR) 1.07 (1.00-1.14); p = 0.039), lower LVEF (OR 0.89 (0.