Preparation and Characterization of Antibacterial Polypropylene Meshes with Covalently Incorporated β-Cyclodextrins and Captured Antimicrobial Agent for Hernia Repair.

Polypropylene (PP) light weight meshes are commonly used as hernioplasty implants. Nevertheless, the growth of bacteria within textile knitted mesh intersections can occur after surgical mesh implantation, causing infections. Thus, bacterial reproduction has to be stopped in the very early stage of mesh implantation. Herein, novel antimicrobial PP meshes grafted with β-CD and complexes with triclosan were prepared for mesh infection prevention. Initially, PP mesh surfaces were functionalized with suitable cold oxygen plasma. Then, hexamethylene diisocyanate (HDI) was successfully grafted on the plasma-activated PP surfaces. Afterwards, β-CD was connected with the already HDI reacted PP meshes and triclosan, serving as a model antimicrobial agent, was loaded into the cyclodextrin (CD) cavity for desired antibacterial functions. The hydrophobic interior and hydrophilic exterior of β-CD are well suited to form complexes with hydrophobic host guest molecules. Thus, the prepared PP mesh samples, CD-TCL-2 and CD-TCL-6 demonstrated excellent antibacterial properties against Staphylococcus aureus and Escherichia coli that were sustained up to 11 and 13 days, respectively. The surfaces of chemically modified PP meshes showed dramatically reduced water contact angles. Moreover, X-ray diffractometer (XRD), differential scanning calorimeter (DSC), and Thermogravimetric (TGA) evidenced that there was no significant effect of grafted hexamethylene diisocyanate (HDI) and CD on the structural and thermal properties of the PP meshes

Controlled Levofloxacin Release and Antibacterial Properties of β-Cyclodextrins-Grafted Polypropylene Mesh Devices for Hernia Repair.

Mesh infection is a major complication of hernia repair. After knitted mesh implantation, bacteria can grow within textile structures causing infection. In this work, polypropylene (PP) mesh devices were two-step grafted with hexamethylene diisocyanate (HDI) and β⁻cyclodexrins (CD) and then loaded with suitable antimicrobial levofloxacin HCL for hernia mesh-infection prevention. First, oxygen plasma was able to create surface roughness, then HDI was successfully grafted onto PP fiber surfaces. Afterwards, CD was covalently grafted onto the HDI treated PP meshes, and levofloxacin HCL (LVFX) was loaded into the CD cavity of the modified meshes. The modified devices were evaluated for sustained antibiotic properties and drug-release profiles in a phosphate buffer, and sustained drug release was observed between interfaces of meshes and aqueous environment. The antibiotic-loaded PP mesh samples demonstrated sustained antibacterial properties for 7 and 10 days, respectively, against both Gram-negative and Gram-positive bacteria. The CD-captured levofloxacin HCL showed burst release after 6 h but later exhibited sustained release for the next 48 h. Among all samples, the modified mesh LVFX-6 was more stable and showed more sustained drug release and could be employed in future clinical applications

Experimental high-intensity three-photon entangled source

We experimentally realize a high-intensity three-photon Greenberger-Horne-Zeilinger (GHZ) entanglement source directly following the proposal by Rarity and Tapster [J. G. Rarity and P. R. Tapster, Phys. Rev. A 59, R35 (1999)]. The threefold coincidence rate can be more than 200 Hz with a fidelity of 0.811, and the intensity can be further improved with moderate fidelity degradation. The GHZ entanglement is characterized by testing the Bell-Mermin inequality and using an entanglement witness operator. To optimize the polarization-entangled source, we theoretically analyze the relationship between the mean photon number of the single-photon source and the probability of parametric down-conversion.Comment: 4 pages, 4 figure

Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP

Graft through ring-opening metathesis polymerization (ROMP) using ruthenium N heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control Here we report the first bivalent-brush polymers, these materials were prepared by graft through ROMP of drug-loaded poly(ethylene glycol) (PEG) based macromonomers (MMs) Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene alkyne-PEG MM via a photocleavable linker ROMP of either or both drug loaded MMs generated brush homo and copolymers with low polydispersities and defined molecular weights. Release of free DOX and CT from these materials was initiated by exposure to 365 nm light All of the CT and DOX polymers were at least 10 fold more toxic to human cancer cells after photoinitiated drug release while a copolymer carrying both CT and DOX displayed 30-fold increased toxicity upon irradiation Graft through ROMP of drug loaded macromonomers provides a general method for the systematic study of structure function relationships for stimuli responsive polymers in biological systems

m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma. © 2019, The Author(s)

Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells

Abstract Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 μmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis