The susceptibility of cancer cells to natural killer (NK) cell-mediated cytotoxicity depends on the balance of activating and inhibitory ligands expressed on their surface. Although many types of cancer cells are killed by NK cells, non-small-cell lung cancer (NSCLC) cells are relatively resistant to NK cell-mediated cytotoxicity. In this study, we showed that several NSCLC cell lines have differential sensitivity to NK cell-mediated cytotoxicity: NCI-H522 cells were highly sensitive, but A549, NCI-H23, NCI-H1915, and NCI-H1299 were resistant. Among activating ligands such as CD48, HLA-A/B/G, ICAM-1, MICA/B, and ULBPs, only CD48 rendered NCI-H522 cells susceptible to NK cell-mediated cytotoxicity, which was proved by using CD48 siRNA and neutralizing antibody. CD48-positive NCI-H522 cells established a more stable contact with NK cells than did CD48-negative A549 and CD48 siRNA cell-transfected NCI-H522 cells. Taken together, these data demonstrate that CD48-positive NSCLC cells might be susceptible to NK cell-mediated cytotoxicity, which provide information on how to stratify NSCLC patients potentially responsive to NK-cell therapy.

As the only component that contacts the ground and rock, the hooves of blue sheep may play a crucial role in their excellent climbing abilities. In this study, we used a combination of techniques, including scanning electron microscopy, infrared spectroscopy and nanoindentation, to characterize the surface morphology, structure, material composition, and mechanical properties of blue sheep hoof and investigate the potential contributions of these properties to the establishment of passive contact stability. Straight and curled microscopic lamellar morphology were found on the hoof surfaces. The cross section of the hoof revealed four layers, and each layer had a unique structure. Finite element analysis was employed to verify that the surface morphology and microstructure effectively contributed to the slip resistance and impact cushioning, respectively. Analyses of the energy and infrared spectra showed that the organic and inorganic substances in different regions of the hoof had similar components but different contents of those components. The hoof was mainly composed of keratin. From the outside to the inside, gradients in both the modulus and hardness were observed. These factors help the hoof alleviate high impact strengths and increase contact stability. These findings further our understanding of the unique mechanism of blue sheep hoof and may help in the development of novel biomimetic materials and mechanical components with enhanced friction and contact stability properties.

It is widely recognized that the accuracy of explicit finite element simulations is sensitive to the choice of interface parameters (i.e. contact stiffness/damping, mesh generation, etc.) and time step sizes. Yet, the effect of these interface parameters on the explicit finite element based solutions of wheel-rail interaction has not been discussed sufficiently in literature. In this paper, the relation between interface parameters and the accuracy of contact solutions is studied. It shows that the wrong choice of these parameters, such as too high/low contact stiffness, coarse mesh, or wrong combination of them, can negatively affect the solution of wheel-rail interactions which manifest in the amplification of contact forces and/or inaccurate contact responses (here called \"contact instability\"). The phenomena of \"contact (in)stabilities\" are studied using an explicit finite element model of a wheel rolling over a rail. The accuracy of contact solutions is assessed by analyzing the area of contact patches and the distribution of normal pressure. Also, the guidelines for selections of optimum interface parameters, which guarantee the contact stability and therefore provide an accurate solution, are proposed. The effectiveness of the selected interface parameters is demonstrated through a series of simulations. The results of these simulations are presented and discussed.

CD226 is an activating receptor expressed on natural killer (NK) cells, CD8+ T cells, and other immune cells. Upon binding to its ligands expressed on target cells, CD226 activates intracellular signaling that triggers cytokine production and degranulation in NK cells. However, the role of CD226 in contact dynamics between NK and cancer cells has remained unclear. Our time-lapse images showed that individual wild-type CD226+ NK cells contacted B16F10 melanoma cells for 23.7 min, but Cd226-/- NK cells only for 12.8 min, although both NK cell subsets showed equal contact frequency over 4 h. On the surface of B16F10 cells, CD226+ cells stayed at the same site with oscillating movement (named stable contact), while Cd226-/- NK cells moved around at a velocity of 4 μm/min (named unstable contact). Consequently, Cd226-/- NK cells did not kill B16F10 cells in vitro and did not inhibit their metastasis into the lung in vivo. Taken together, our data demonstrate that CD226 enables prolonged stable interaction between NK and cancer cells, which is needed for efficient killing of cancer cells.

BACKGROUND: Preclinical work suggests factors including catheter orientation and contact consistency during individual radiofrequency ablations influence lesion size. Our aim was to investigate factors affecting catheter contact in the left atrium (LA) and their effects on ablation.
RESULTS: A total of 2,298 8-second static LA mapping points were studied in 30 patients undergoing ablation for AF (16 in AF, 14 sinus rhythm [SR], 18 remote robotic navigation [RRN] procedures) using a contact force (CF) sensing catheter. CF variability (CFV: difference between 20 Hz-sampled CF waveform mean peak and trough) increased with mean CF, Spearman\'s ρ = 0.6, P < 0.005. Catheter drift correlated weakly with CF (Pearson\'s correlation -0.06, P = 0.005). CFV was higher in SR than AF and with RRN (P < 0.001). In AF, there was less catheter drift for RRN than manual navigation points but the converse was true in SR. In 747 static 30 second LA ablations, the influence of contact parameters on ablation efficacy was compared by multivariate analysis of impedance drop during ablation: a lesser drop suggesting reduced efficacy. For a given force time integral (FTI), increased CFV (>5 g) and locational drift (>3.5 mm), perpendicular contact, SR and RRN usage were associated with a lesser impedance drop with ablation (P < 0.005 for each), suggesting reduced efficacy.
CONCLUSIONS: Beyond the FTI, the quality of catheter contact influences ablation efficacy, and clinical catheter contact is affected by multiple factors, including the atrial rhythm and catheter navigation mode. Maximal efficacy is provided by parallel contact with CFV ≤5 g, catheter drift ≤3.5 mm, and manual navigation.