Green fabrication of seedbed-like Flammulina velutipes polysaccharides-derived scaffolds accelerating full-thickness skin wound healing accompanied by hair follicle regeneration.

A novel seedbed-like scaffold was firstly fabricated by the "frozen sectioning" processing method using Flammulina velutipes as a raw material. The Flammulina velutipes polysaccharides scaffold is composed of a natural structure imitating the "ground" (connected and aligned hollow tubes with porous walls). Meanwhile, its biologically active components include polysaccharides and proteins, mimicking the "plant nutrition" in the seedbed. To further optimize the ground and nutrition components, Flammulina velutipes polysaccharides-derived scaffolds (FPDSs) were fabricated via the treatment of original Flammulina velutipes polysaccharides scaffold (labeled FPS) by NaOH, cysteine (labeled as FPS/NaOH, FPS/Cys, respectively). FPDSs were characterized by SEM, FTIR, XRD, water absorption and retention, and mechanical evaluations. From the results, FPS/NaOH and FPS/Cys lost the characteristic big tubes of original strips and had higher water absorption capacities comparing to FPS. Simultaneously, FPS/NaOH had better ductility, FPS/Cys had showed increased stiffness. Biological activities of FPDSs were tested against different types of bacteria exhibiting excellent anti-bacterial activity, and FPS/NaOH and FPS/Cys had dramatically higher anti-bacterial activity than FPS. The cytocompatibility of FPDSs was evaluated utilizing mouse fibroblast cell line (L929), and all FPDSs showed good cytocompatibility. The FPDSs were further applied to a rat full-thickness skin wound model, and they all exhibited obviously accelerated re-epithelialization, among which FPS/NaOH showed the greatest efficiency. FPS/NaOH could shorten the wound-healing process as evidenced by dynamic alterations of the expression levels of specific stagewise markers in the healing areas. Similarly, FPS/NaOH can efficiently induce hair follicle regeneration in the healing skin tissues. In summary, FPDSs exhibit potential functions as seedbeds to promote the regeneration of the "seed" including hair follicles and injured skin, opening a new avenue for wound healing.

An Ordered Lasso and Sparse Time-Lagged Regression.

We consider regression scenarios where it is natural to impose an order constraint on the coefficients. We propose an order-constrained version of ℓ 1-regularized regression (Lasso) for this problem, and show how to solve it efficiently using the well-known Pool Adjacent Violators Algorithm as its proximal operator. The main application of this idea is to time-lagged regression, where we predict an outcome at time t from features at the previous K time points. In this setting it is natural to assume that the coefficients decay as we move farther away from t, and hence the order constraint is reasonable. Potential application areas include financial time series and prediction of dynamic patient outcomes based on clinical measurements. We illustrate this idea on real and simulated data.