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This study investigated the influence of surface wettability on competitive protein adsorption and the initial attachment of osteoblasts. A thin-film coating of hexamethyldisiloxane (HMDSO) and subsequent O(2)-plasma treatment was carried out on substrates with a mirror surface in order to create a wide range of wettabilities. The adsorption behavior of fibronectin (Fn) and albumin (Alb) in both individual and competitive mode, and the initial attachment of mouse osteoblastic cells (MC3T3-E1) over a wide range of wettabilities were investigated. The contact angle of HMDSO coatings without O(2)-plasma treatment against double-distilled water was more than 100 degrees, whereas it dramatically decreased after the O(2)-plasma treatment to almost 0 degrees, resulting in super-hydrophilicity. Individually, Fn adsorption showed a biphasic inclination, whereas Alb showed greater adsorption to hydrophobic surfaces. In the competitive mode, in a solution containing both Fn and Alb, Fn showed greater adsorption on hydrophilic surfaces, whereas Alb predominantly adsorbed on hydrophobic surfaces. The initial attachment of osteoblastic cells increased with an increase in surface wettability, in particular, on a super-hydrophilic surface, which correlated well with Fn adsorption in the competitive mode. These results suggest that Fn adsorption may be responsible for increasing cell adhesion on hydrophilic surfaces in a body fluid or culture media under physiological conditions.

Anti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK. By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.

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Surface wettability is an important physicochemical property of biomaterials, and it would be more helpful for understanding this property if a wide range of wettability are employed. This study focused on the effect of surface wettability on fibroblast adhesion over a wide range of wettability using a single material without changing surface topography. Plasma polymerization with hexa methyldisiloxane followed by oxygen (O 2 ) plasma treatment was employed to modify the surfaces. The water contact angle of sample surfaces varied from 106 degrees (hydrophobicity) to almost 0 degrees (super-hydrophilicity). O 2 -functional groups were introduced on polymer surfaces during O 2 -plasma treatment. The cell attachment study confirmed that the more hydrophilic the surface, the more fibroblasts adhered in the initial stage that includes on super-hydrophilic surfaces. Cells spread much more widely on the hydrophilic surfaces than on the hydrophobic surfaces. There was no significant difference in fibroblast proliferation, but cell spreading was much greater on the hydrophilic surfaces. These findings suggest the importance of the surface wettability of biomaterials on initial cell attachment and spreading. The degree of wettability should be taken into account when a new biomaterial is to be employed. Further research of surface wettability on adhesive molecules is necessary for a better understanding of this property.

We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received 1 to 2 islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-α blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels, and C-peptide production) and for adverse events associated with the study protocol. Of the 6 recipients, 5 were insulin-independent at 1 year, and 4 continue to be insulin-independent at a mean of 3.4 ± 0.4 years posttransplant. None of the 6 recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ±21.2 mL/min/1.73m2 pretransplant to 82.6 ±19.1 mL/min/1.73m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in 4 of 6 recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.

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Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD.