Current perspectives in pulmonary surfactant — Inhibition, enhancement and evaluation

Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.     

The avian malaria parasite Plasmodium gallinaceum causes marked structural changes on the surface of its host erythrocyte

Using a combination of atomic force, scanning and transmission electron microscopy, we found that avian erythrocytes infected with the avian malaria parasite Plasmodium gallinaceum develop 60 nm wide and 430 nm long furrow-like structures on the surface. Furrows begin to appear during the early trophozoite stage of the parasite’s development. They remain constant in size and density during the course of parasite maturation and are uniformly distributed in random orientations over the erythrocyte surface. In addition, the density of furrows is directly proportional to the number of parasites contained within the erythrocyte. These findings suggest that parasite-induced intraerythrocytic processes are involved in modifying the surface of host erythrocytes. These processes may be analogous to those of the human malaria parasite P. falciparum, which induces knob-like protrusions that mediate the pathogenic adherence of parasitized erythrocytes to microvessels. Although P. gallinaceum-infected erythrocytes do not seem to adhere to microvessels in the host chicken, the furrows might be involved in the pathogenesis of P. gallinaceum infections by some other mechanism involving host-pathogen interactions.     

A Novel Type of Coupling Between Proline and Galactoside Transport in Escherichia coli

Exit of thiomethylgalactoside (TMG) from preloaded cells induced the accumulation of proline. Likewise, proline exit stimulated TMG accumulation. Since a proton ionophore (carbonyl-cyanide-m-chlorophenylhydrazone) abolished these effects, a proton-motive force was implicated as the “intermediate” in the coupling reaction. The evidence suggests that the exit of TMG resulted in proton exit, which produced either a membrane potential (inside negative) or a pH gradient (outside acid) or both. This inwardly directed protonmotive force provided the energy for proline entry and accumulation. Thus the energy coupling was not via a common transport protein but by proton movements which coupled the two separate H⁺-dependent transport processes.     

Validation of the Boussinesq equation for use in traction field determination

Cell traction force plays an important role in many biological processes. Several traction force microscopy methods have been developed to determine cell traction forces based on the Boussinesq solution. This approach, however, is rooted in a half-space assumption. The purpose of this study was to determine the error induced in the half-space assumption using a finite element method (FEM). It demonstrates that displacement error between the FEM and the Boussinesq equation can be used to measure the accuracy of the Boussinesq equation, although singularity exists in the loading point. For one concentrated force, significant difference between the FEM and the Boussinesq equation occurs in the whole field; this difference decreases with an increase in the plate thickness. However, in the case of the balanced forces, the offset of the balanced forces decreases the errors in the middle area. Overall, this study demonstrates that increasing the thickness of the polyacrylamide gel is important for reducing the error of the Boussinesq equation when determining the displacement field of the gel under loads.     

Efficient Plasmonic Au/CdSe Nanodumbbell for Photoelectrochemical Hydrogen Generation beyond Visible Region

In this communication, light harvesting and photoelectrochemical (PEC) hydrogen generation beyond the visible region are realized by an anisotropic plasmonic metal/semiconductor hybrid photocatalyst with precise control of their topology and heterointerface. Controlling the intended configuration of the photocatalytic semiconductor to anisotropic Au nanorods' plasmonic hot spots, through a water phase cation exchange strategy, the site‐selective overgrowth of a CdSe shell evolving from a core/shell to a nanodumbbell is realized successfully. Using this strategy, tip‐preferred efficient photoinduced electron/hole separation and plasmon enhancement can be realized. Thus, the PEC hydrogen generation activity of the Au/CdSe nanodumbbell is 45.29 µmol cm^?2 h^?1 (nearly 4 times than the core/shell structure) beyond vis (λ > 700 nm) illumination and exhibits a high faradic efficiency of 96% and excellent stability with a constant photocurrent for 5 days. Using surface photovoltage microscopy, it is further demonstrated that the efficient plasmonic hot charge spatial separation, which hot electrons can inject into CdSe semiconductors, leads to excellent performance in the Au/CdSe nanodumbbell.     

AFM对黄精赞育胶囊优选方处理前后大鼠弱精子超微结构的观察研究

目的:应用原子力显微镜技术实现对大鼠精子超微结构的实时成像,对比观察中药作用前后弱精子超微结构的变化.方法:制作少弱精症大鼠模型;运用非接触模式原子力显微镜技术对比观察正常精子和病理性精子在中药作用前后超微结构的动态变化.结果:获得精子头体、颈部和鞭毛等部位的实时超微结构图像.结论:AFM可直接探测精子头体的各种畸形,实现对精子全貌的观测.通过修复弱精子超微结构的病理形态学缺陷可能是黄精赞育胶囊优选方改善弱精子质量的机制之一.     

RAPID ALDOSTERONE-INDUCED CELL VOLUME INCREASE OF ENDOTHELIAL CELLS MEASURED BY THE ATOMIC FORCE MICROSCOPE

Atomic force microscopy (AFM) is a useful technique for imaging the surface of living cells in three dimensions. The authors applied AFM to obtain morphological information of individual cultured endothelial cells of bovine aorta under stationary and strain conditions and to simultaneously measure changes in cell volume in response to aldosterone. This mineralocorticoid hormone is known to have acute, non-genomic effects on intracellular pH, intracellular electrolytes and inositol-1,4,5-triphosphate production. In this study whether endothelial cells under tension change their volume in response to aldosterone was tested. Such changes were already shown in human leukocytes measured by Coulter counter. In contrast to leukocytes that are more or less spherical and live in suspension, endothelial cells exhibit a complex morphology and adhere to a substrate. Thus, measurements of discrete cell volume changes in endothelial cells under physiological condition is only feasible with more sophisticated techniques. By using AFM we could precisely measure the absolute cell volume of individual living endothelial cells. Before the addition of aldosterone the cell volume of mechanically stressed endothelial cells mimicking arterial blood pressure was 1827±172fl. Cell volume was found to increase by 28% 5min after hormone exposure. Twenty-five minutes later cell volume was back to normal despite the continuous presence of aldosterone in the medium. Amiloride, a blocker of the plasma membrane Na⁺/H⁺exchanger prevented the initial aldosterone-induced volume increase. Taken together, AFM disclosed a transient swelling of endothelial cells induced by the activation of an aldosterone sensitive plasma membrane Na⁺/H⁺exchanger.     

Single molecule studies of antibody-antigen interaction strength versus intra-molecular antigen stability

We investigated molecular recognition of antibodies to membrane-antigens and extraction of the antigens out of membranes at the single molecule level. Using dynamic force microscopy imaging and enzyme immunoassay, binding of anti-sendai antibodies to sendai-epitopes genetically fused into bacteriorhodopsin molecules from purple membranes were detected under physiological conditions. The antibody/antigen interaction strength of 70-170 pN at loading rates of 2-50 nN/second yielded a barrier width of x = 0.12 nm and a kinetic off-rate (corresponding to the barrier height) of k(off) = 6s(-1), respectively. Bacteriorhodopsin unfolding revealed a characteristic intra-molecular force pattern, in which wild-type and sendai-bacteriorhodopsin molecules were clearly distinguishable in their length distributions, originating from the additional 13 amino acid residues epitope in sendai purple membranes. The inter-molecular antibody/antigen unbinding force was significantly lower than the force required to mechanically extract the binding epitope-containing helix pair out of the membrane and unfold it (126 pN compared to 204 pN at the same loading rate), meeting the expectation that inter-molecular unbinding forces are weaker than intra-molecular unfolding forces responsible for stabilizing native conformations of proteins.     

Comparison of radiomic features in diagnostic CT images with and without contrast enhancement in the delayed phase for NSCLC patients

PurposeTo compare radiomic features extracted from diagnostic computed tomography (CT) images with and without contrast enhancement in delayed phase for non-small cell lung cancer (NSCLC) patients.MethodsDiagnostic CT images from 269 tumors [non-contrast CT, 188 (dataset NE); contrast-enhanced CT, 81 (dataset CE)] were enrolled in this study. Eighteen first-order and seventy-five texture features were extracted by setting five bin width levels for CT values. Reproducible features were selected by the intraclass correlation coefficient (ICC). Radiomic features were compared between datasets NE and CE. Subgroup analyses were performed based on the CT acquisition period, exposure value, and patient characteristics.ResultsEighty features were considered reproducible (0.5 ≤ ICC). Twelve of the sixteen first-order features, independent of the bin width levels, were statistically different between datasets NE and CE (p < 0.05), and the p-values of two first-order features depending on the bin width levels were reduced with narrower bin widths. Sixteen out of sixty-two features showed a significant difference, regardless of the bin width (p < 0.05). There were significant differences between datasets NE and CE with older age, lighter body weight, better performance status, being a smoker, larger gross tumor volume, and tumor location at central region.ConclusionsContrast enhancement in the delayed phase of CT images for NSCLC patients affected some of the radiomic features and the variability of radiomic features due to contrast uptake may depend largely on the patient characteristics.