In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway.

Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 µM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors.

Pharmacological perspectives and molecular mechanisms of coumarin derivatives against virus disease.

Infections caused by viruses are one of the foremost causes of morbidity and mortality in the world. Although a number of antiviral drugs are currently used for treatment of various kinds of viral infection diseases, there is still no available therapeutic agent for most of the viruses in clinical practice. Coumarin is a chemical compound which is found naturally in a variety of plants, it can also be synthetically produced possessing diverse biological effects. More recently, reports have highlighted the potential role of coumarin derivatives as antiviral agents. This review outlines the advances in coumarin-based compounds against various viruses including human immunodeficiency virus, hepatitis virus, herpes simplex virus, Chikungunya virus and Enterovirus 71, as well as the structure activity relationship and the possible mechanism of action of the most potent coumarin derivatives.

Interagency collaboration within the city emergency management network: a case study of Super Ministry Reform in China.

Emergencies continue to become ever more complex; responding to them, therefore, often is beyond the capabilities and capacities of any single public agency. Hence, collaboration among these actors is necessary to prepare for, respond to, and recover from such events. This seldom occurs in an effective or efficient manner, however. Drawing on resource dependence theory and the concept of social capital, this paper reveals that different types of collaborative relationships exist within the collaborative network. Super Ministry Reform of Emergency Management in China serves as a case in point. By evaluating network efficiency and classifying the collaborative relationships of involved government agencies, four types are identified: resource-redundant; resource-complementary; resource-dependent; and resource-isolated. The different influences of collaborative relationships explain why the reform is not that effective, although it has led to the merger of several core departments in the emergency management network. The findings are a reminder to consider network structure and collaboration types when engaging in institutional design.

Coumarin Derivative N6 as a Novel anti-hantavirus Infection Agent Targeting AKT.

Hantaviruses are globally emerging zoonotic viruses that can cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe, which is primarily caused by Hantaan virus (HTNV) infection, results in profound morbidity and mortality. However, no specific treatment is available for this disease. Coumarin derivatives have been reported as antiviral molecules, while studies about the bioactivity of coumarin derivatives against HTNV infection are limited. To study the potential antiviral activity of coumarin derivatives, 126 coumarin derivatives are synthesized, and their inhibitory activity against HTNV is analyzed in vitro. Among these compounds, N6 inhibits HTNV with relatively high selectivity index at 10.9, and the viral titer of HTNV is reduced significantly after 5, 10, and 20 µM N6 treatments. Furthermore, the administration of N6 at the early stage of HTNV infection can inhibit the replication and production of infectious HTNV in host cell, this therapeutic efficacy is confirmed in HTNV-infected newborn mice at the early stage of infection. The molecular docking results show that N6 forms interactions with the key amino acid residues at its active site, and reveals several molecular interactions responsible for the observed affinity, and the treatment of N6 can inhibit the expression of p (Ser473)Akt and HTNV nucleocapsid protein significantly. As such, these observations demonstrate that coumarin derivative N6 might be used as a potential agent against HTNV infection.

A new coumarin compound DCH combats methicillin-resistant Staphylococcus aureus biofilm by targeting arginine repressor.

Staphylococcus aureus infection is difficult to eradicate because of biofilm formation and antibiotic resistance. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection necessitates the development of a new agent against bacterial biofilms. We report a new coumarin compound, termed DCH, that effectively combats MRSA in vitro and in vivo and exhibits potent antibiofilm activity without detectable resistance. Cellular proteome analysis suggests that the molecular mechanism of action of DCH involves the arginine catabolic pathway. Using molecular docking and binding affinity assays of DCH, and comparison of the properties of wild-type and ArgR-deficient MRSA strains, we demonstrate that the arginine repressor ArgR, an essential regulator of the arginine catabolic pathway, is the target of DCH. These findings indicate that DCH is a promising lead compound and validate bacterial ArgR as a potential target in the development of new drugs against MRSA biofilms.

Core-shell ZnO@C:N hybrids derived from MOFs as long-cycling anodes for lithium ion batteries.

A core-shell hybrid of ZnO and nitrogen-doped carbon (ZnO@C:N) is designed as a long-cycling anode for LIBs. The ZnO@C:N hybrid has a high initial capacity of 1116 mA h g-1 and a reversible capacity of 608 mA h g-1 after 500 cycles at 0.1 A g-1. The unique core-shell structure, high conductivity due to nitrogen doping, and uniform solid electrolyte interphase (SEI) film formed in the electrode are revealed to result in the remarkable electrochemical performances of the ZnO@C:N electrodes.

A cobalt-pyrrole coordination compound as high performance cathode catalyst for direct borohydride fuel cells.

Pyrrole and cobalt nitrate were used as nitrogen and metal sources respectively to synthesize a dinitratobis(polypyrrole)cobalt(ii) (Co(polypyrrole)2(NO3)2) adduct as the precursor of a Co-pyrrole/MPC catalyst. Pyrrole has the capability of polymerization and coordination with Co(ii). Taking this advantage, the Co(polypyrrole)2(NO3)2 coordination can form a long-chain structure with abundant and robust Co-N bonds, contributing to significantly increased catalytic sites in the product catalyst. As a result, the obtained Co-pyrrole/MPC (MPC = macroporous carbon) catalyst exhibited high ORR catalytic activity in alkaline media and excellent performance in direct borohydride fuel cell (DBFC). A peak power density up to 325 mW cm-2 was achieved at ambient condition, outperforming the commercialized Pt/XC-72 benchmark containing 28.6 wt% Pt. The construction of long-chain coordination precursor was verified playing a key role in the electrochemical improvement of Co-pyrrole/MPC catalyst in DBFC.

In vitro and in vivo anti-biofilm activity of pyran derivative against Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The development of bacterial biofilm can cause severe chronic infections and antibiotic resistance. Therefore, it poses a significant threat to public health. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) are two major pathogens that can cause biofilm-associated infections, which leads to the urgent necessity of developing new agents with biofilm-forming inhibitory ability. METHODS: A series of pyran derivatives were synthesized and characterized, and their in vitro anti-biofilm activity against S. aureus and P. aeruginosa were measured by minimal biofilm inhibitory concentration assay and FITC dye staining. The in vivo antibiofilm therapeutical effects were evaluated in S. aureus induced tissue cage infection mice model and P. aeruginosa induced urinary tract catheter infection rat model. RESULTS: Several pyran derivatives showed the in vitro anti-biofilm activity against S. aureus and P. aeruginosa, and the activity of these compounds was not mediated through the accessory gene regulator (agr) quorum sensing system of S. aureus. One of these pyran derivatives, namely 2-amino-4-(2,6-dichlorophenyl)-3-cyano-5-oxo-4H,5H-pyrano[3,2c]chromene, exhibited significant inhibitory biofilm-formation activity in S. aureus tissue cage infection mice model and in the P. aeruginosa-infected urinary tract catheters of experimental rats. CONCLUSIONS: The data indicated that this pyran derivative is a possible lead compound that can be used for the development of novel anti-biofilm agents against S. aureus and P. aeruginosa infection.

A facile self-templating synthesis of carbon frameworks with tailored hierarchical porosity for enhanced energy storage performance.

Herein, we present a facile synthesis of hierarchical carbon frameworks with microporous skeletons and interconnected meso/macropores by employing poly(vinylidene chloride-co-methyl acrylate)-b-polystyrene copolymers as precursors. The obtained porosity can be tuned over a broad range via well-selected block proportions of the precursor, enabling its advantageous applications in target-oriented energy storage systems.

Foldable interpenetrated metal-organic frameworks/carbon nanotubes thin film for lithium-sulfur batteries.

Lithium-sulfur batteries are promising technologies for powering flexible devices due to their high energy density, low cost and environmental friendliness, when the insulating nature, shuttle effect and volume expansion of sulfur electrodes are well addressed. Here, we report a strategy of using foldable interpenetrated metal-organic frameworks/carbon nanotubes thin film for binder-free advanced lithium-sulfur batteries through a facile confinement conversion. The carbon nanotubes interpenetrate through the metal-organic frameworks crystal and interweave the electrode into a stratified structure to provide both conductivity and structural integrity, while the highly porous metal-organic frameworks endow the electrode with strong sulfur confinement to achieve good cyclability. These hierarchical porous interpenetrated three-dimensional conductive networks with well confined S8 lead to high sulfur loading and utilization, as well as high volumetric energy density.

Synthesis and pharmacological evaluations of 4-hydroxycoumarin derivatives as a new class of anti-Staphylococcus aureus agents.

OBJECTIVES: Due to the increasing prevalence of drug-resistant Staphylococcus aureus infection, we develop novel 4-hydroxycoumarin derivatives as antimicrobials. METHODS: The antibacterial activity of 4-hydroxycoumarin derivatives against drug-susceptive S. aureus (ATCC 29213) and methicillin-resistant S. aureus (MRSA) were evaluated using minimal inhibitory concentration (MIC) assay; the activity of favourable compound was further observed using bacterial growth curves assay and in the MRSA infection mice. KEY FINDINGS: Compared with dihydropyran derivatives, compound 1 as one of biscoumarins showed most potent activity with MIC values of 4-8 µg/ml and apparently inhibited the growth rate of S. aureus ATCC 29213 and USA300 strain in concentrations of both 16 and 32 mg/ml. In the mice infected with MRSA USA300, administration of 5 mg/kg compound 1 improved the animal survival rate to 66.7%, and improved the pathological change in lung tissue compared with the infection model animals. No significant cytotoxicity of compound 1 was observed on the umbilical vein endothelial cells (HUVECs) under the concentration of 800 µg/ml. CONCLUSION: Compared with the dihydropyran derivatives, biscoumarins exhibited more promising activity against both drug-sensitive and drug-resistant S. aureus, and it is efficacious in treating MRSA infections in mouse models with a favourable safety in human cells.

Correction: In situ study of the catalytic mechanism for the oxygen reduction reaction on a polypyrrole modified carbon supported cobalt hydroxide cathode in direct borohydride fuel cells.

Correction for 'In situ study of the catalytic mechanism for the oxygen reduction reaction on a polypyrrole modified carbon supported cobalt hydroxide cathode in direct borohydride fuel cells' by Haiying Qin et al., Phys. Chem. Chem. Phys., 2013, 15, 9070-9074.

Synthesis, antibacterial activities, and theoretical studies of dicoumarols.

Four dicoumarols (DC, 2-PyDC, 3-PyDC and 4-PyDC) were synthesized and characterized via IR, (1)H NMR, HRMS, and single crystal X-ray crystallography. Two classical intramolecular O-H···O hydrogen bonds (HBs) stabilized their structures. The total HB energies in DC, 2-PyDC, 3-PyDC and 4-PyDC were calculated with the density functional theory (DFT) [B3LYP/6-31G*] method. The in vitro antibacterial activity of DC, 2-PyDC, 3-PyDC and 4-PyDC against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC) was evaluated by observing the minimum inhibitory concentration and time-kill curves. The results showed that among all the compounds, 2-PyDC exhibited the most potent antibacterial activity.

In situ study of the catalytic mechanism for the oxygen reduction reaction on a polypyrrole modified carbon supported cobalt hydroxide cathode in direct borohydride fuel cells.

An in situ test method has been developed to study the Co(OH)2-PPy-BP cathode status during DBFC operation. It is found that some Co(2+) ions are oxidized to Co(3+) present in CoOOH during cell operation. A mechanism for the oxygen reduction reaction on the Co(OH)2-PPy-BP cathode in alkaline media has been proposed.