Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Influence of electroosmotic treatment on the hydro-mechanical behaviour of clayey silts: preliminary experimental results

Preliminary results of an investigation focused on the influence of electrokinetic treatment on the mechanical and hydraulic behaviour of clayey soils are presented. The experimental programme aims at providing a contribution to the sustainability of contaminant extraction or containment via electroosmosis. Changes in the hydraulic and mechanical properties of two illitic clayey soils, subjected to a DC electric field, were investigated. Samples of the two soils were subjected to electrokinetic filtration, for different periods of time, and under different constant loads. Afterwards, they were tested under one-dimensional compression to detect changes in stiffness and hydraulic conductivity due to the electrical treatment. After the application of a DC field for a few hours, a small reversible increment in the average soil stiffness was observed, with respect to the untreated soil, while the hydraulic conductivity was not affected substantially. Dramatic changes of the mechanical and hydraulic soil properties, correlated to changes of the soil pH, were observed following non-conditioned electrokinetic treatment with duration of the order of days.     

Comparison of electrocardiographic data (P waves): test of a shape-based approach

We tested a method for comparing ECG signals (P waves), in a sample of 10 normal males. In each subject, sets of 219 body surface ECGs were simultaneously recorded during tidal respiration. Only beats at end expiration and peak inspiration were considered. The beats of each group were subdivided into two subgroups of the same size (about 30 beats) and separately averaged. The two averaged beats at end expiration, assumed to be equal, were compared in order to estimate the noise variance (sigma2), i.e., the lowest value of variance at which the beats were statistically similar (P less than 0.05). At the same value of sigma2, the beat at end expiration significantly differed from that at peak inspiration. By considering the individual leads, significant differences were found in more than 50% of the 219 ECGs, in specific thoracic areas. The data indicated that the method can reveal differences between P waves occurring during tidal respiration and provide information on the topographical distribution of the differences.     

Time-independent mechanical properties of a chromium-manganese austenitic steel weldment

Room and elevated (450° C) temperature tensile data and room temperature notch impact data on weld metal and a welded joint of 10 wt % Cr-17.5 wt % Mn austenitic steel, a candidate material for thermonuclear fusion reactor first wall and blanket structures, are reported and discussed in terms of the microstructural features observed.     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

A controlled comparison of thermal biofeedback and relaxation training in the treatment of essential hypertension: II. Effects on cardiovascular reactivity.

Compared progressive muscle relaxation (PMR), thermal biofeedback (BFB), and drug withdrawal (DW) as possible substitutes for 2nd-stage (sympatholytic) antihypertensive medications, using 73 hypertensive adults. Reactivity (heart rate, systolic blood pressure, and diastolic blood pressure) to 3 stressors (mental arithmetic, cold pressor, and negative mental imagery) was measured before and after PMR, BFB, and DW. PMR led to more reductions in some aspect of reactivity than did BFB. Reductions in reactivity were seen more for mental arithmetic and systolic blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A low momentum tagged antineutron beam

The operating performances of a low-momentum (< 270 MeV/c) tagged beam are reported. The beam is obtained by means of the charge exchange reaction n on a liquid hydrogen target. The neutron associated to the in the two-body reaction is used for the determination of the energy and direction. The measured total rate of tagged is 8.02 ± 0.03 × 10⁻⁵ per incident at 300 MeV/c.