Design, synthesis, biological evaluation and molecular docking study of novel pleuromutilin derivatives containing substituted benzoxazole as antibacterial agents.

A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (-1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).

Design, synthesis, and biological evaluation of pleuromutilin derivatives containing 1,2,4-triazole linker.

A series of thioether pleuromutilin derivatives containing 1,2,4-triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). The results of time-kill study and postantibiotic effect study indicated that compound 72 could inhibit the growth of MRSA quickly (-2.16 log10 CFU/mL) and showed certain postantibiotic effect (PAE) time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.30 and 1.35 h) against MRSA. Furthermore, the binding mode between compound 72 and 50S ribosome of MRSA was explored by molecular docking and five hydrogen bonds were formed between compound 72 and 50S ribosome.

Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti-MRSA agents.

A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined by the broth dilution method. Among these derivatives, compound 58 exhibited superior in vitro antibacterial effect against MRSA (minimal inhibitory concentration [MIC] = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). Compound 58 possessed a faster bactericidal kinetic and a longer post-antibiotic effect time against MRSA than tiamulin. Meanwhile, at 8 µg/mL concentration, compound 58 did not display obviously cytotoxic effect on the RAW 264.7 cells. In addition, compound 58 (-2.04 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (-1.02 log10 CFU/mL) in reducing MRSA load in mice thigh infection model. In molecular docking study, compound 58 can successfully attach to the 50S ribosomal active site (the binding free energy is -8.11 kcal/mol). Therefore, compound 58 was a potential antibacterial candidate for combating MRSA infections.

Effects of the Yaw Angle on Air Drag Reduction for Various Riblet Surfaces.

Biomimetic riblet surfaces, such as blade, wavy, sinusoidal, and herringbone riblet surfaces, have widespread applications for drag reduction in the energy, transportation, and biomedicine industries. The drag reduction ability of a blade riblet surface is sensitive to the yaw angle, which is the angle between the design direction of the riblet surface and the average flow direction. In practical applications, the average flow direction is often misaligned with the design direction of riblet surfaces with different morphologies and arrangements. However, previous studies have not reported on the drag reduction characteristics and regularities related to the yaw angle for surfaces with complex riblet microstructures. For the first time, we systematically investigated the aerodynamic drag reduction characteristics of blade, wavy, sinusoidal, and herringbone riblet surfaces affected by different yaw angles. A precisely adjustable yaw angle measurement method was proposed based on a closed air channel. Our results revealed the aerodynamic behavior regularities of various riblet surfaces as affected by yaw angles and Reynolds numbers. Riblet surfaces with optimal air drag reduction were obtained in yaw angles ranging from 0 to 60° and Reynolds numbers ranging from 4000 to 7000. To evaluate the effects of the yaw angle, we proposed a criterion based on the actual spanwise spacing (d+) of microstructure surfaces with the same phase in a near-wall airflow field. Finally, we established conceptual models of aerodynamic behaviors for different riblet surfaces in response to changes in the airflow direction. Our research lays a foundation for practical various riblet surface applications influenced by yaw angles to reduce air drag.

Design, synthesis, biological evaluation and molecular docking studies of novel pleuromutilin derivatives containing nitrogen heterocycle and alkylamine groups.

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The in vitro antibacterial activity of these semisynthetic derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus AD3, and S.aureus 144) were evaluated by the broth dilution method. Compound 13 was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 µg/mL). Furthermore, compound 13 was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound 13 exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound 13 showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 µg/mL. Molecular docking study revealed that compound 13 can effectively bind to the active site of the 50S ribosome (the binding free energy = -9.66 kcal/mol).

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker.

A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85-110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 µg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.

Optical Diagnostic Based on Functionalized Gold Nanoparticles.

Au nanoparticles (NPs) possess unique physicochemical and optical properties, showing great potential in biomedical applications. Diagnostic spectroscopy utilizing varied Au NPs has become a precision tool of in vitro and in vivo diagnostic for cancer and other specific diseases. In this review, we tried to comprehensively introduce the remarkable optical properties of Au NPs, including localized surfaces plasmon resonance (LSPR), surface-enhanced Raman scattering (SERS), and metal-enhanced fluorescence (MEF). Then, we highlighted the excellent works using Au NPs for optical diagnostic applications. Ultimately, the challenges and future perspective of using Au NPs for optical diagnostic were discussed.

A simple and high-performance cellulose nanocrystal based biocatalytic Pickering emulsion system for pharmaceutical molecule vitamin E nicotinate.

The use of Pickering emulsions for biocatalysis is gaining increased attention. However, the extensive application is greatly limited due to the enzyme inactivation. Herein, a biocatalytic Pickering emulsion with high-performance utilizing cellulose nanocrystals immobilized lipases (CNCs-Lps) particles as stabilizer is advanced and applied for the synthesis of Vitamin E nicotinate. CNCs-Lps display high activity and reusability due to the construction of biocatalytic microreactor in the O/W emulsion system. The yield of vitamin E nicotinate ester reached up to 83 %. More importantly, the CNCs-Lps can be reused due to the similar principles to microreactors in Pickering emulsions. Reusability test showed that the CNCs-Lps could be recovered from the emulsion system by centrifugation and the yield of vitamin E nicotinate retains 78 % of initial value after five cycles, demonstrating overwhelming advantage than the fair counterpart with free lipases.

An inner filter effect-based fluorescent aptasensor for sensitive detection of kanamycin in complex samples using gold nanoparticles and graphene oxide quantum dots.

In this work, a label-free fluorescent aptasensor based on the inner filter effect (IFE) between gold nanoparticles (AuNPs) and graphene oxide quantum dots (GOQDs) was developed for the detection of kanamycin in complex samples. AuNPs are capable of functioning as the fluorescence absorber of GOQDs because of the complementary overlap between their absorption spectra and the emission spectra of GOQDs. AuNPs can effectively quench the fluorescence of GOQDs via the IFE and modulate it with their aggregation state. In the presence of kanamycin, the aptamer is released from the surface of AuNPs, leading to their salt-induced aggregation and the fluorescence recovery of GOQDs. Under the optimum conditions, the fluorescence intensity of GOQDs was linearly proportional to the concentration of kanamycin over the range from 5 to 600 nM, with a detection limit of 3.6 nM. Moreover, the fluorescent aptasensor was successfully applied for kanamycin detection in complex samples (milk, honey and serum), which might hold great promise for kanamycin detection in food safety control and clinical research.

Diclofenac and eugenol hybrid with enhanced anti-inflammatory activity through activating HO-1 and inhibiting NF-κB pathway in vitro and in vivo.

A series of diclofenac hybrid molecules were synthesized and evaluated for their NO-inhibitory ability in LPS-induced RAW 264.7 macrophage cells. Among them, compound 1 showed the highest NO-inhibitory ability (approximately 66%) and no significant cytotoxicity. Compound 1 exhibited superior NF-κB-inhibitory ability compared to diclofenac through the activation of Nrf2/HO-1 signaling pathway in RAW 264.7. 20 mg/kg compound 1 resulted in remarkable colitis improvement in dextran sulfate sodium (DSS)-induced mice model by up-regulating HO-1 and down-regulating phosphorylation level of NF-κB p65. Moreover, 50 mg/kg dose of compound 1 showed a lower ulcerogenic potential compared to diclofenac in rats. The diclofenac-eugenol hybrid (compound 1) may serve as a novel anti-inflammatory agent based on its role in inhibiting the NF-κB signaling pathway and activating HO-1 expression with no toxicity in vitro and in vivo.

Low Air Drag Surface via Multilayer Hierarchical Riblets.

Riblets inspired by shark skin exhibit a great air drag reduction potential in many industries, such as the aircraft, energy, and transportation industries. Many studies have reported that blade riblets attain the highest air drag reduction ability, with a current limit of ∼11%. Here, we propose multilayer hierarchical riblets (MLHRs) to further improve the air drag reduction ability. MLHRs were fabricated via a three-layer hybrid mask lithography method, and the air drag reduction ability was studied in a closed air channel. The experimental results indicated that the maximum air drag reduction achieved with MLHRs in the closed channel was 16.67%, which represents a 52% higher reduction than the highest previously reported. Conceptual models were proposed to explain the experiments from a microscopic perspective. MLHRs enhanced the stability of lifting and pinning vortices, while vortices gradually decelerated further, reducing the momentum exchange occurring near the wall. This verified that MLHRs overcome the current air drag reduction limit of riblets. The conceptual models lay a foundation to further improve the air drag reduction ability of riblets.

Lignin Nanosphere-Supported Cuprous Oxide as an Efficient Catalyst for Huisgen [3+2] Cycloadditions under Relatively Mild Conditions.

In this work, low-cost lignin nanospheres were fabricated and further applied as an efficient and sustainable support for preparing cuprous oxide (Cu2O) "green" catalyst by using electrospraying technology. The unalloyed lignin, a special three-dimensional molecular structure, was successfully processed into uniform nanospheres under an electrospraying condition. The synthesized lignin-supported Cu2O catalyst had a well-defined nanosphere structure, and Cu2O nanoparticles with sizes less than 30 nm were supported by exposed layers of lignin nanospheres. There were C⁻O⁻Cu bonds formed between the lignin nanospheres and the metallic nanoparticles. The lignin nanospheres and the lignin nanosphere-supported catalyst werfe characterized by utilizing XRD, SEM, TEM, XPS, EDS, and TGA. The immobilization of Cu2O nanoparticles on the lignin nanospheres was beneficial for dispersion of the Cu2O nanoparticles and preventing their aggregation, which could cause catalyst deactivation, which favored the Huisgen [3+2] cycloaddition reaction. The triazole synthesis results indicated that the lignin nanosphere-supported Cu2O catalyst had a high catalytic performance with 99% yield under solvent-free conditions. Furthermore, the as-synthesized catalyst could be recycled for four times without significantly losing its catalytic activity.

Electrospun cellulose acetate supported Ag@AgCl composites with facet-dependent photocatalytic properties on degradation of organic dyes under visible-light irradiation.

Electrospun cellulose acetate (CA) membrane was employed as a support that provided sites for AgCl crystals in situ growth. The Ag@AgCl crystals on electrospun CA composites with exposed {100} and {111} facets were fabricated at room temperature by a double diffusion technique. The crystal structure, morphology, composition, and absorption light ability of CA supported Ag@AgCl were characterized utilizing X-ray powder diffraction (XRD), scanning electron microscopy (SEM), attenuated total reflection-infrared intensity (ATR-IR), X-ray photoelectron spectroscopy measurements (XPS), energy dispersive spectrometer (EDS) and ultraviolet-visible (UV-vis) diffuse reflectance spectra, respectively. The photocatalytic activity of the catalysts was evaluated using methyl orange (MO) as a target. The CA supported cubic Ag@AgCl catalyst exhibited much higher catalytic activity than octahedral catalyst in terms of the degradation of MO under visible light. The 10mg CA based cubes could completely degrade MO (10 mg L(-1)) in 160 min. The photocatalyst still exhibited a good catalytic ability after three times.