Design and Synthesis of 4-Fluorophenyl-5-methylene-2(5H)-furanone Derivatives as Potent Quorum Sensing Inhibitors.

Quorum sensing inhibitors (QSIs) are a class of compounds that can reduce the pathogenicity of bacteria without affecting bacterial growth. In this study, we designed and synthesized four series of 4-fluorophenyl-5-methylene-2(5H)-furanone derivatives and evaluated their QSI activities. Among them, compound 23e not only showed excellent inhibitory activity against various virulence factors but also significantly enhanced the inhibitory activity of antibiotics ciprofloxacin and clarithromycin against two strains of Pseudomonas aeruginosa in vitro. What is even more exciting is that it remarkably increased the antibacterial effect in vivo in combination with ciprofloxacin in the bacteremia model infected with P. aeruginosa PAO1. Moreover, 23e had little hemolytic activity to mouse erythrocytes. Further, the results of GFP reporter fluorescence strain inhibition and ß-galactosidase activity inhibition experiments demonstrated that 23e simultaneously targeted the three quorum sensing systems in P. aeruginosa. As a result, compound 23e could be used as an effective QSI for further development against bacterial infections.

Design and synthesis of benzochromene derivatives as AcrB inhibitors for the reversal of bacterial multidrug resistance.

A series of novel benzo[h]chromene compounds were designed, synthesized and evaluated for their biological activity as AcrB inhibitors. The compounds were assessed for their ability to potentiate the effect of antibiotics. Compounds with antibiotic-potentiating effects were then evaluated for inhibition of Nile Red efflux, and for off-target effects including activity on the outer and inner bacterial membranes and toxicity. Six compounds were identified to reduce the MIC values of at least one of the tested antibiotics by at least 4-fold, and further reduced the MICs in the presence of a membrane permeabilizer. The identified compounds were also able to inhibit Nile Red efflux at concentrations between 50 µM and 200 µM. The compounds did not disrupt the bacterial outer membrane nor display toxicity in a nematode model (Caenorhabditis elegans). The 4-methoxyphenoxy)propoxy derivative compound G6 possessed the most potent antibacterial potentiation with erythromycin by 8-fold even without the presence of a membrane permeabilizer. Furthermore, H6, G6, G10 and G11 completely abolished the Nile Red efflux at a concentration of 50 µM. The 3,4-dihydro-2H-benzo[h]chromen-5-yl)(morpholino)methanone core appears to be a promising chemical skeleton to be further studied in the discovery of more putative AcrB inhibitors.

Extreme risk spillover from uncertainty to carbon markets in China and the EU-A time varying copula approach.

Emissions Trading Schemes (ETS) rely on market signals like price stability and predictability, which are affected by the volatility of the financial market and the energy market. Risk is an important indicator of price stability. Using a time-varying copula method, this study analyzes the extreme risk impact of uncertainties (including Economic policy uncertainty (EPU), financial market (VIX) and energy market uncertainty (OVX)) on carbon markets in China and the European Union (EU). This paper also measures the asymmetry of that risk spillover; that is, we identify the impact of increasing and decreasing uncertainties on ETS market risk (stability). Our results show that increased uncertainty in economic policies, financial markets and energy markets will lead to a decline in ETS prices in China and the EU. Chinese and European ETS market risks are most significantly affected by energy market uncertainty changes, and least affected by economic uncertainty changes. Although European ETS markets are riskier than Chinese ETS markets, European ETS prices are more stable. Downside and upside analysis show that risk spillovers to Chinese and European carbon markets are significantly asymmetric and dynamic. Specifically, the downward volatility of uncertainty has a stronger risk impact on ETS than the upward volatility does. Our research provides a useful reference for policy makers to improve ETS market price stability and guide expectations, providing investors with a reliable method to predict market risks.

Non-Farm Employment, Farmland Renting and Farming Ability: Evidence from China.

In the process of China's urbanization, non-farm employment and farmland rental activity are closely correlated. Using data from a survey on rural households in three Chinese provinces, this article examines the relationship between farmland renting activity and non-farm employment with simultaneous equations that consider the farming ability of farmers. Our results are fourfold. First, farmland renting-out promotes non-farm employment, while farmland renting-in reduces non-farm employment. Second, non-farm employment encourages farmland renting-out and decreases farmland renting-in. Third, farming ability increases farmland renting-in but decreases non-farm employment. Fourth, non-farm employment decreases the farming ability of farmers. Based on our empirical findings, we would suggest that the Chinese government further reforms its land system in rural areas, which could better facilitate land-use-right transfer and promote farmland rental market.

One-Pot Template-Free Strategy toward 3D Hierarchical Porous Nitrogen-Doped Carbon Framework in Situ Armored Homogeneous NiO Nanoparticles for High-Performance Asymmetric Supercapacitors.

The composites based on graphitic carbon and transitional metal oxides are regarded as one of the most promising electrochemical materials owing to the synergistic combination of the advantages of both superior electrical conductivity and high pseudocapacitance. In this work, a simple one-pot template-free strategy for the preparation of three-dimensional hierarchical porous nitrogen-doped carbon framework in situ armored NiO nanograins (NCF/NiO) by an ammonia-induced method assisted by the pyrolysis of a decomposable salt is reported. Due to such unique architecture and homogeneously dispersed nanoparticles, the as-prepared NCF/NiO-2 hybrid exhibits a large specific surface area (412.3 m2 g-1), a high specific capacitance (1074 F g-1 at 1 A g-1), good rate capability (820 F g-1 at 20 A g-1), and outstanding cycling performance (almost no decay after 5000 cycles). Moreover, the solid-state asymmetric supercapacitor, assembled with NCF/NiO-2 and NCS electrodes, can achieve a high cell potential of 1.6 V and deliver a superior specific capacitance of 113 F g-1 at 1 A g-1 with a maximum energy density of 40.18 W h kg-1 at a power density of 800 W kg-1, consequently, giving rise to stable cycling performance (94.3% retention over 5000 cycles). The prepared devices are shown to power 20 green light-emitting diodes efficiently. These encouraging results open up a wide horizon for developing novel carbon-supported metal oxide electrode materials for high rate energy conversion and storage devices.

Constructing an Anisotropic Triple-Pass Tubular Framework within a Lyophilized Porous Gelatin Scaffold Using Dexamethasone-Loaded Functionalized Whatman Paper To Reinforce Its Mechanical Strength and Promote Osteogenesis.

In bone tissue engineering (BTE), most of the currently developed scaffolds still lack the ability to demonstrate high porosity and high mechanical strength simultaneously or the ability to maintain bioactivity and sustained release of loaded biofactors. In this work, we constructed an anisotropic triple-pass tubular framework within a lyophilized porous GEL scaffold using FP, which was prepared by coating DEX-covered Whatman paper (WP) using the silk fibroin (SF) membrane with ß-sheet conformation. This novel structural design endowed the functionalized paper frame (FPF)/scaffold implant high porosity, high mechanical strength, and sustained DEX delivery capability. Specifically, its porosity was as high as 88.2%, approximating that of human cancellous bone. The pore diameters of the implant ranged from 50 to 350 µm with an average pore diameter of 127.7 µm, indicating proper pore sizes for successful diffusion of essential nutrients/oxygen and bone tissue-ingrowth. Owing to the construction of double-network-like structure, the FPF/scaffold implant demonstrated excellent mechanical properties both in dry (174.7 MPa in elastic modulus and 14.9 MPa in compressive modulus) and wet states (59.0 MPa in elastic modulus and 3.3 MPa in compressive modulus), indicating its feasibility for in vivo implantation. Besides, the FPF/scaffold implant exhibited long-term DEX releasing behavior (over 50 days) with constant release rate in phosphate buffered saline (PBS). Murine osteoblasts MC3T3-E1 cultured in the porous FPF/scaffold implant had excellent viability. Furthermore, the cells cocultured with the FPF/scaffold implant showed positive proliferation, osteogenic differentiation, and calcium deposition. Twenty-eight days after implantation, extensive osteogenesis was observed in the rats treated with the FPF/scaffold implants. The anisotropic triple-pass tubular framework of the FPF/scaffold implant demonstrates structural similarities to the long bone. Therefore, this novel FPF/scaffold implant could be a better alternative for long bone defect repair.

Constructing multi-component organic/inorganic composite bacterial cellulose-gelatin/hydroxyapatite double-network scaffold platform for stem cell-mediated bone tissue engineering.

Bacterial cellulose/hydroxyapatite (BC/HAp) composite had good bioaffinity but its poor mechanical strength limited its widespread applications in bone tissue engineering (BTE). Bacterial cellulose/gelatin (BC/GEL) double-network (DN) composite had excellent mechanical properties but was seldom used in biomedical fields. In this regard, a multi-component organic/inorganic composite BC-GEL/HAp DN composite was synthesized, which combined the advantages of BC/HAp and BC/GEL. Compared with BC/GEL, the BC-GEL/HAp exhibited rougher surface topography and higher thermal stability. Compression and tensile testing indicated that the mechanical strength of the BC-GEL/HAp was greatly reinforced compared with BC/HAp and was even higher than that of BC/GEL. In vitro cell culture demonstrated that the rat bone marrow-derived mesenchymal stem cells (rBMSCs) cultured on the BC-GEL/HAp showed better adhesion and higher proliferation and differentiation potential than the cells cultured on BC/GEL. We hope the BC-GEL/HAp composite could be used as ideal bone scaffold platform or biomedical membrane in the future.

A facile method for the preparation of chitosan-based scaffolds with anisotropic pores for tissue engineering applications.

To date, great efforts have been made to prepare different kinds of isotropic tissue engineering (TE) scaffolds. However, little attention has been paid to anisotropic porous scaffolds in spite of many examples of their excellent performances. In this work, a facile method termed "ammonia-induced method" (AIM) was proposed and applied to generate anisotropic pores in chitosan (CS)-based scaffolds. The pore structures of these scaffolds were studied in detail. In order to clarify the rationale behind this process, a speculative explanation was provided on basis of the experimental results and the theory of Uras (Uras & Devlin, 2000). Compression tests indicated that the mechanical strengths of these scaffolds were sufficient for TE applications. In vitro cell culture showed that MC3T3-E1 cells cultivated in the pores of these scaffolds had positive proliferation potential. We anticipated that this novel AIM could inspire research not only in TE but also in other fields.

A novel chitosan-tussah silk fibroin/nano-hydroxyapatite composite bone scaffold platform with tunable mechanical strength in a wide range.

Currently, great efforts have been made to enhance the mechanical strength of bone tissue engineering (BTE) scaffolds, which are composed of biopolymeric matrices and inorganic nano-fillers. But the tunability of mechanical strength in a wide range for BTE scaffolds has seldom been investigated in spite of the great importance of this performance. In this work, a chitosan-tussah silk fibroin/hydroxyapatite (CS-TSF/HAp) hydrogel was synthesized by using a novel in situ precipitation method. Through in situ inducing the conformation transition of TSF in the CS-TSF/HAp hydrogel, which could be monitored by XRD, FT-IR, TGA, and DTA, the elastic modulus and fracture strength of the final CS-TSF/HAp composite could be tailored in a wide range without changing its composition, morphology, roughness, and crystal structures. The elastic modulus of the CS-TSF/HAp composite ranged from ∼250 to ∼400MPa while its fracture strength ranged from ∼45 to ∼100MPa. In order to clarify the rationale behind this process, a speculative explanation was provided. In vitro cell culture indicated that MC3T3-E1 cells cultured on the CS-TSF/HAp composite had positive adhesion, proliferation, and differentiation potential. We believed that the CS-TSF/HAp composite could be used as an ideal scaffold platform for cell culture and implantation of bone reconstruction.