It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H 2 O 2 ). These features of the tumor microenvironment may provide physiochemical conditions that are suitable for selective tumor therapy and recognition. Here, for the first time, we demonstrate that a type of graphene oxide nanoparticle (N-GO) can exhibit peroxidase-like activities (i.e., can increase the levels of reactive oxygen species (ROS)) under acidic conditions and catalyze the conversion of H 2 O 2 to ROShydroxyl radicals (HO • ) in the acidic microenvironment in Hela tumors. The concentrated and highly toxic HO • can then trigger necrosis of tumor cells. In the microenvironment of normal tissues, which has a neutral pH and low levels of H 2 O 2 , N-GOs exhibit catalase-like activity (scavenge ROS) that splits H 2 O 2 into O 2 and water (H 2 O), leaving normal cells unharmed. In the recognition of tumors, an inherent redox characteristic of dopamine is that it oxidizes to form dopamine− quinine under neutral (pH 7.4) conditions, quenching the fluorescence of N-GOs; however, this characteristic has no effect on the fluorescence of N-GOs in an acidic (pH 6.0) medium. This pH-controlled response provides an active targeting strategy for the diagnostic recognition of tumor cells. Our current work demonstrates that nanocatalytic N-GOs in an acidic and high-H 2 O 2 tumor microenvironment can provide novel benefits that can reduce drug resistance, minimize side effects on normal tissues, improve antitumor efficacy, and offer good biocompatibility for tumor selective therapeutics and specific recognition.

Nanoscale delivery based on polyethylene glycol (PEG)ylated graphene oxide (GO-PEG) merits attention for biomedical applications owing to its functional surface modification, superior solubility/biocompatibility and controllable drug release capability. However, impaired skin regeneration in applications of these fascinating nanomaterials in diabetes is still limited, and critical issues need to be addressed regarding insufficient collagen hyperplasia and inadequate blood supply. Therefore, a high-performance tissue engineering scaffold with biocompatible and biodegradable properties is essential for diabetic wound healing. Natural and artificial acellular dermal matrix (ADM) scaffolds with spatially organized collagen fibers can provide a suitable architecture and environment for cell attachment and proliferation. Here, a novel collagen-nanomaterial-drug hybrid scaffold was constructed from GO-PEG-mediated quercetin (GO-PEG/Que)-modified ADM (ADM-GO-PEG/Que). The resulting unique and versatile hybrid scaffold exhibited multiple advantages, including the following: a biocompatible, cell-adhesive surface for accelerating mesenchymal stem cell (MSC) attachment and proliferation; superior stability and adjustability of the conduction potential of quercetin for inducing the differentiation of MSCs into adipocytes and osteoblasts; and a biodegradable nanofiber interface for promoting collagen deposition and angiogenesis in diabetic wound repair. This study provides new prospects for the design of innovative GO-PEG-based collagen hybrid scaffolds for application in efficient therapeutic drug delivery, stem cell-based therapies, tissue engineering and regenerative medicine.

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We establish the composition-diamond lemma for associative nonunitary Rota-Baxter algebras of weight λ. To give an application, we construct a linear basis for a free commutative and nonunitary Rota-Baxter algebra, show that every countably generated Rota-Baxter algebra of weight 0 can be embedded into a two-generated Rota-Baxter algebra, and prove the 1 2 -PBW theorems for dendriform dialgebras and trialgebras.

A theoretical model is established for dealing with second-harmonic generation (SHG) in type I collagen excited by linearly polarized light focused by a microscope. With this model, the effects of the polarization angle alpha, numerical aperture (NA), as well as the ratio of hyperpolarizability rho=beta(xxx)beta(xyy) on SHG emission have been investigated. Simulation results reveal that SHG emission power changes periodically as alpha. The use of lower NA leads to weaker SHG emission but is more concentrated in two closer lobes, whereas more distributed emission in two detached lobes appear at higher NA. As the introduction of polarization direction, which is not along with the fiber axis (alpha not equal0 deg), one more element beta(xyy) is valid in our case than beta(xxx) alone, while their ratio rho plays a very important role for collagen features characterization. SHG emission with rho shows complicated modality that SHG emission is different at different alpha and not symmetric at +/-rho except at alpha=0 deg, suggesting the important impact of polarization working on rho for SHG emission. Our theoretical simulation results provide useful clues for experimental study of microscopic SHG emission in collagen excited by linearly polarized beam.

Quasiphase matching (QPM) is a widely used theory in crystal to analyze the character of second-harmonic generation (SHG) emitted from it. Based on the structural features of collagen type I, where the constituted fibrils in collagen function as a crystal which has the structure of two-dimensional (2D) quasicrystalline, in this paper, we use the QPM theory on collagen for SHG emission direction study under the excitation of laser light through a microscope. The effects of numerical aperture NA, as well as the structural parameters, such as QPM order (m,l) and collagen period a=d1+d2 associated with the fibrils diameter (d1), packing density and interfibrils structure (d2), etc., on SHG emission angle φ have been investigated. Our theoretical results show that collagen period a has threshold effect on φ to present forward or backward SHG emission and NA has minor influence on this threshold value a. Collagen period of a has more significant influence on SHG emission angle φ when a is smaller than the threshold value. In reality, we realize that diameter of collagen fibrils d1 plays a major role on forward or backward emission of SHG. Here, for example, (we assume d1=a/2), when d1≤95 nm [(m,l)=(1,0)], the backward SHG shows up at any magnitude of NA, while when d1≥150 nm [(m,l)=(1,0)], SHG presents forward emission feature under all circumstances. Between them, SHG emits from forward direction to backward direction as the increase in NA. The QPM order (m,l) has nonlinear impact on SHG emission angle φ and has different degrees of influence on different collagen period a. Our theoretical results are highly consistent with the experiments results demonstrated by other researchers and provide a proper explanation of the phenomenon of appreciable backward SHG signals appearing in collagen type I. Our established theoretical model of applying QPM theory in 2D quasicrystalline fibrils is therefore confirmed to be a suitable model for dealing with SHG in type I collagen.

C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing. ADM scaffolds were fabricated from nondiabetic mouse skin through decellularization processing and incorporated with AMD3100 to construct ADM-AMD3100 scaffold. Full-thickness cutaneous wound in streptozotocin (STZ)-induced diabetic mice were treated with ADM, AMD3100, or ADM-AMD3100. 21 days after treatment, wound closure in ADM-AMD3100-treated mice was more complete than ADM group and AMD3100 group, and it was accompanied by thicker collagen formation. Correspondingly, diabetic mice treated with ADM-AMD3100 demonstrated prominent neovascularization (higher capillary density and vascular smooth muscle actin), which were accompanied by up-regulated mRNA levels of SDF-1 and enhanced migration of CXCR4 in the granulation tissue. Our results demonstrate that ADM scaffold provide perfect niche for loading AMD3100 and ADM-AMD3100 is a promising method for diabetic wound healing mainly by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.

BackgroundAdult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair.MethodsIn this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline).ResultsIn vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature TH1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of TH1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin.ConclusionsCurcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.