Dynamic Surface Activity of a Fully Synthetic Phospholipase-Resistant Lipid/Peptide Lung Surfactant

This study examines the surface activity and resistance to phospholipase degradation of a fully-synthetic lung surfactant containing a novel diether phosphonolipid (DEPN-8) plus a 34 amino acid peptide (Mini-B) related to native surfactant protein (SP)-B. Activity studies used adsorption, pulsating bubble, and captive bubble methods to assess a range of surface behaviors, supplemented by molecular studies using Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and plasmon resonance. Calf lung surfactant extract (CLSE) was used as a positive control.DEPN-8+1.5% (by wt.) Mini-B was fully resistant to degradation by phospholipase A(2) (PLA(2)) in vitro, while CLSE was severely degraded by this enzyme. Mini-B interacted with DEPN-8 at the molecular level based on FTIR spectroscopy, and had significant plasmon resonance binding affinity for DEPN-8. DEPN-8+1.5% Mini-B had greatly increased adsorption compared to DEPN-8 alone, but did not fully equal the very high adsorption of CLSE. In pulsating bubble studies at a low phospholipid concentration of 0.5 mg/ml, DEPN-8+1.5% Mini-B and CLSE both reached minimum surface tensions <1 mN/m after 10 min of cycling. DEPN-8 (2.5 mg/ml)+1.5% Mini-B and CLSE (2.5 mg/ml) also reached minimum surface tensions <1 mN/m at 10 min of pulsation in the presence of serum albumin (3 mg/ml) on the pulsating bubble. In captive bubble studies, DEPN-8+1.5% Mini-B and CLSE both generated minimum surface tensions <1 mN/m on 10 successive cycles of compression/expansion at quasi-static and dynamic rates.These results show that DEPN-8 and 1.5% Mini-B form an interactive binary molecular mixture with very high surface activity and the ability to resist degradation by phospholipases in inflammatory lung injury. These characteristics are promising for the development of related fully-synthetic lipid/peptide exogenous surfactants for treating diseases of surfactant deficiency or dysfunction

Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery

Low molecular weight heparin (LMWH) is often used to prevent perioperative venous thrombosis after surgery, but aspirin is also recommended by academics. Studies were searched in electronic databases until February 24, 2023. We performed a meta-analysis to evaluate the safety and efficacy of aspirin and LMWH for venous thromboembolism (VTE) prophylaxis in patients after orthopedic surgery. The outcomes were death from any causes, deep vein thrombosis (DVT), pulmonary embolism (PE), etc. This study was registered with INPLASY, number 202320117. Six randomized controlled trials enrolled 13,851 patients with postoperative joint surgery. The risk of DVT was comparable between the two groups when aspirin was combined with mechanical devices (RR 0.61 [95% CI 0.27–1.39], I² = 62%, P = 0.24). No significant differences in all cause death, PE, wound infection, and wound complication were found between the aspirin and LMWH groups. In this meta-analysis, the mortality rate was comparable between the aspirin and LMWH groups. However, aspirin alone had a higher risk of DVT than LMWH. Based on the results of this meta-analysis, we suggest aspirin combined with mechanical devices for VTE prophylaxis in patients after orthopedic surgery

Deformation Test System of Transmission Tower Based on Binocular Vision Method

A test system to measure the deformation of the transmission tower based on binocular vision method is introduced in this work. The test system can achieve the accurate monitoring of the transmission tower deformation, and provide deformation data for the reliability analysis of the transmission tower provides both in static and dynamic measurement. The test system is successfully applied in a tower type test

Deformation Test System of Transmission Tower Based on Binocular Vision Method

A test system to measure the deformation of the transmission tower based on binocular vision method is introduced in this work. The test system can achieve the accurate monitoring of the transmission tower deformation, and provide deformation data for the reliability analysis of the transmission tower provides both in static and dynamic measurement. The test system is successfully applied in a tower type test

Mean association and dissociation kinetic rate constants (k_on, k_off) and equilibrium dissociation constant KD calculated from plasmon resonance measurements for liposomes of DEPN-8 or DPPC flowing past a chip-linked Mini-B monolayer.

*<p>Liposomes of DEPN-8 or DPPC in running buffer (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.005% Surfactant P20, pH 7.4) were flowed past a monolayer of Mini-B linked via Cys4 and Cys27 to a C5M sensor chip in a Biacore 3000 system (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001039#s4" target="_blank"><u>Methods</u></a>). Mean kinetic rate constants (k_on, k_off) and the equilibrium dissociation constant (KD = k_off/k_on) were determined from curve fitting analyses of plasmon resonance results at six different lipid concentrations (0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 µg/ml for each lipid).</p

Spectroscopic behavior of Mini-B and DEPN-8.

<p><u>Panel A</u>: CD spectrum for Mini-B in trifluoroethanol (TFE); <u>Panel B</u>: FTIR spectrum for DEPN-8; <u>Panel C</u>: FTIR spectral differences for Mini-B in DEPN-8 (dashed line) compared to Mini-B in TFE (solid line). In Panel A, mean residue ellipticity (MRE) averaged over eight scans is plotted against wavelength for Mini-B in 4∶6 (v:v) TFE:10 mM phosphate buffer, pH 7.4. The double minimum at ∼208 and 222 nm is indicative of a high α-helical content. In Panel B, the spectrum for DEPN-8 multilayers (100 µg lipid, arbitrary absorbance units) has a “C-O-C” ether linkage-associated absorption band centered at a wavenumber of 1072 cm⁻¹. In Panel C, the IR spectrum of Mini-B in TFE (solid line) has a peak at 1655 cm⁻¹ indicating high α-helix levels, while the peak at 1658 cm⁻¹ and high-field shoulder at 1678 cm⁻¹ for Mini-B in DEPN-8 (dashed line) indicates an increase in turn/bend conformation with a decreased but still prominent α-helix content. See text for discussion.</p

Dynamic surface activity of DEPN-8+1.5% or 3% Mini-B compared to CLSE on the captive bubble surfactometer.

<p>Minimum and maximum surface tensions are shown for DEPN-8+1.5% or 3% by weight Mini-B and CLSE on a captive bubble surfactometer during 10 cycles of rapid compression (20 cycles/min) following slow compression as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001039#pone-0001039-g005" target="_blank">Figure 5</a>. Surface tension values are Mean±SEM for at least three separate experiments. See text for details.</p

Resistance of DEPN-8+1.5% by weight Mini-B to degradation by phospholipase A₂ (PLA₂) compared to calf lung surfactant extract (CLSE).

<p>Data are mean±SEM for n = 3. DEPN-8+1.5% by weight Mini-B was incubated <i>in vitro</i> with PLA₂ (0.1 Units/ml) for 30 min at 37°C, and degradation was assessed by measuring lipid classes in weight percent based on phosphate analysis of bands on thin layer chromatography. Results for CLSE in the presence and absence of PLA₂ utilized identical methods as reported previously by Wang et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001039#pone.0001039-Wang3" target="_blank">[30]</a>.</p