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JNK3, a protein kinase of the MAPK family that is potently activated by a variety of environmental stress and pro-inflammatory cytokines, has been recognized as an important therapeutic target for several neurodegenerative diseases. However, due to the long development cycle and the cost of R&D, no related drugs have been released. By applying the CoMFA and CoMSIA methods, QSAR models that explore the structure-activity relationship of the JNK3 inhibitors are established and validated, the parameters are satisfactory (q2 = 0.774, r2 = 0.991 for CoMFA model and q2 = 0.666, r2 = 0.990 for CoMSIA model) and base on which a series of novel molecules are designed. Molecular docking is conducted to verify the potential of the new compounds, the results shows promising activity. We speculated that the series of compounds S1–S11 might have some therapeutic activity in the c-jnk3 pathway, particularly the “S8” may prove to be the best one, which provided useful guidance for the design of new and efficient subtype selective JNK3 inhibitors.

In this work, we show that the quality of the precursor and the thin film preparation strongly affect the optoelectronic properties of the 2D perovskite BA2PbI4. 2D perovskites with alkylammonium organic cations such as butylammonium (BA) are relatively soft structures that exhibit large dynamic disorder and phase variations. Here we show, by a variety of spectroscopy techniques (steady state absorption, photoluminescence and ultrafast transient absorption), that at temperatures below the phase transition (253 K) the material exhibits excitonic features from the room temperature phase (due to incomplete structural transition) and a broadband emission at 560–600 nm (due to self-trapped excitons) with varied relative intensities depending on the precursors and processing conditions. This suggests that the processing conditions have a large influence on the crystallization and introduction of extrinsic defect impurities directly affecting the optoelectronic properties. Making absolute statements about the properties of BA2PbI4 requires improved control over the materials thin film deposition and a better understanding of the role of the lattice vibrational dynamics and extrinsic defects on the exciton dynamics.

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection-induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.

Peramivir is an efficacious neuraminidase (NA) inhibitor for treatment of influenza by intravenous administration. However, the efficacy of peramivir toward the H275Y mutant is appreciably reduced. To address this drawback, conjugation of peramivir with caffeic acid is devised in this study to enhance the binding affinity with neuraminidases. The C2-OH group of peramivir is elaborated to link with caffeate derivatives, giving the desired conjugates 8 and 9 that possess potent NA inhibitory activity against both wild-type and H275Y viruses with the IC50 values in nanomolar range. The molecular modeling reveals that the caffeate moiety of conjugate 9 prefers to reside in the 295-cavity of H275Y neuraminidase, thus providing additional hydrogen bonds and hydrophobic interactions to compensate the reduced binding affinity of the peramivir moiety due to Glu-276 dislocation in H275Y mutant. In comparison with peramivir, the lipophilicity of conjugates 8 and 9 also increases by incorporation of the caffeate moiety. Thus, conjugates 8 and 9 offer better effect to protect MDCK cells from infection of H275Y virus with low EC50 value (∼17 nM). Administration of conjugates 8 or 9 by oral gavage is effective in treatment of mice that are infected by lethal dose of wild-type or H275Y influenza viruses. Considering drug metabolism, since the ester linkage in conjugate 8 is susceptible to hydrolysis in plasma, conjugate 9 with robust amide linkage may be a better candidate for development into orally available anti-influenza drug that is also active to mutant viruses.

Two new tetralone derivatives, named cyclopalosides A (1) and B (2), were isolated from the leaves of Cyclocarya paliurus by column chromatography on silica gel, reversed-phase C18 silica gel and preparative HPLC. Their chemical structures were established on the basis of extensive analyses of spectroscopic data. Their structural characteristic is tetralone glycoside with a caffeoyl unit. The antioxidant activities of compound 1 were evaluated by using hydroxyl, superoxide anion, and DPPH radical scavenging assay.

C14H13NO, monoclinic, P21/n (no. 14), a = 9.2770(7) Å, b = 8.4582(6) Å, c = 13.4430(12) Å, β = 98.199(8)°, V = 1044.05(14) Å3, Z = 4, R gt (F) = 0.0484, wR ref (F 2) = 0.1151, T = 100 K.

A new derivative of syringic acid, stageobester A (1) and two iridoid glycosides which including a new one, stageoboside A (2), were isolated from the roots of Stachys geobombycis. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all the isolates were tested for their antioxidant capacity. Compounds 1 and 2 showed moderate antioxidant activities against DPPH radical, with IC50 values of 113.33 ± 1.53 and 40.33 ± 2.08 mg/L, respectively.

Five caffeoyl phenylethanoid glycosides, including two new ones linderruelliosides A (1) and B (2), were isolated from the leaves and stems of Lindernia ruellioides. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all these compounds were tested for their anti-HBV activity. Compounds 1, 3, and 4 showed anti-HBV activities, with IC50 values of 54.87, 30.74, and 69.02 μM for HBsAg and 26.70, 5.17, and 7.08 μM for HBeAg, respectively.

Nutrients in the substrate are important for plant growth, particularly during the development of vegetable seedlings. The continued development of intensive methods to produce seedlings has made growing healthy and high-grade seedlings a requirement for nurseries. This study evaluated the effect of nitrogen (N), phosphorus (P), and potassium (K) on the root activity, dry weight, and chlorophyll content in leaves of Brassica oleracea seedlings. D-optimal design was used in this study because of its accuracy. A total of 10 treatments (T1–T10) were designed, and different concentrations were chosen in the following ranges: N (0.6-5.0 g·kg-1), P (0.2-6.0 g·kg-1), and K (0.7-7.0 g·kg-1). Our study shows that the application of N, P, and K to the substrate significantly influenced the growth of B. oleracea seedlings. T6 significantly increased root activity, root dry weight, chlorophyll content in leaves when compared with the control T1, which had added nutrient concentrations at normal levels. However, the addition of high levels of N (5.0 g·kg-1) with high (7.0 g·kg-1) or low (0.7 g·kg-1) levels of K (T2 and T9) not only significantly decreased the root dry weight but also decreased leaf area. Our results suggest that N, P, and K can be added to the substrate at an appropriate ratio to grow vigorous B. oleracea seedlings under intensive seedling production conditions. The present results give insight into the nutrient requirements during early growth of B. oleracea seedlings in growth substrate.

Alkaline proteases have biotechnological importance due to their activity and stability at alkaline pH. 56 bacteria, capable of growing under alkaline conditions were isolated and their alkaline protease activities were carried out at different parameters to determine their optimum alkaline protease production conditions. Seven isolates were showed higher alkaline protease production capacity than the reference strains. The highest alkaline protease producing isolates (103125 U/g), E114 and C265, were identified as Bacillus licheniformis with 99.4% and Bacillus mojavensis 99.8% based on 16S rRNA gene sequence similarities, respectively. Interestingly, the isolates identified as Bacillus safensis were also found to be high alkaline protease producing strains. Genotypic characterizations of the isolates were also determined by using a wide range of molecular techniques (ARDRA, ITS-PCR, (GTG)5-PCR, BOX-PCR). These different techniques allowed us to differentiate the alkaliphilic isolates and the results were in concurrence with phylogenetic analyses of the 16S rRNA genes. While ITS-PCR provided the highest correlation with 16S rRNA groups, (GTG)5-PCR showed the highest differentiation at species and intra-species level. In this study, each of the biotechnologically valuable alkaline protease producing isolates was grouped into their taxonomic positions with multi-genotypic analyses.

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.

Diabetes mellitus (DM) is a metabolic disease attracted worldwide concerns, which severely impairs peoples' quality of life and is attributed to several life-threatening complications, including atherosclerosis, nephropathy and retinopathy. The current therapies for DM include mainly oral anti-diabetic drugs and insulin. However, continuous use of these causes insulin resistance and side-effects, and the demand of effective, nontoxic and affordable drugs for DM patients is eager. Several previous studies have shown that non-toxic biological macromolecules, mainly polysaccharides, possess prominent efficacies on DM. Based on these encouraging observations, a great deal of efforts have been focused on discovering anti-diabetic polysaccharides for the development of effective therapeutics for DM. This review focuses on the advancements in the anti-diabetic efficacy of various natural polysaccharides and polysaccharide complexes from 2010 to 2015.

A series of Bronsted acidic ionic liquids (ILs) were prepared and used for Biginelli-type condensation reaction among aromatic aldehydes, urea or thiourea and cyclopentanone. Through this reaction, the synthesis of various pyrimidinones could be achieved. Of interest, it was found that the reaction was efficiently catalyzed by a novel, eco-friendly functionalized IL [C 3 SO 3 HDoim]HSO 4 , which could be reused for at least 7 times without significantly loss of catalytic activity. The reaction proceeded efficiently at 80 °C to afford the desired products in good yield (up to 96%). In addition, a possible mechanism that accounted for the IL [C 3 SO 3 HDoim]HSO 4 -catalyzed reaction was proposed.

Molybdenum trioxide (MoO3) microrods, nanofibers, and nanoplates were synthesized via the hydrothermal method and high-temperature calcination method, respectively. Then the MoO3 was added into polyurethane elastomer, respectively. The flame retardancy and smoke suppression of the composites added with different MoO3 were studied by thermal gravimetric analysis, cone calorimeter, and smoke density. The results show that the three kinds of MoO3 with different morphologies could promote the formation of char and possess flame retardancy and smoke suppression, and MoO3 nanofibers exhibit a higher degree of flame retardancy, and 1 wt% addition could make the peak heat release rate of polyurethane elastomer composites reduce from 881.6 kW m−2 for a pure sample to 343.4 kW m−2, a decrease by 61.0%. As for smoke suppression, MoO3 nanoplates possess the best smoke suppression; 5 wt% could decrease a pure sample's smoke density by 41.3% from 361 to 212. Moreover, the char residue of composites after combustion was analyzed by Raman spectra and X-ray photoelectron spectroscopy, and the flame retardancy and smoke suppression mechanisms of MoO3 were discussed.

Two series of polynitro heterocyclic compounds with three conformations are designed based on the obtained dodecahydrodiimidazo [4,5-b:4′,5′-e]pyrazine “565” structure. First, the conformations including boat, chair, and plane, are optimized at B3PW91/6-311+G(d,p) level and some important properties are calculated. Based on the bond order, bond dissociation enthalpies and molecular energy analysis, it is found that the boat conformation owns lower energy and better bond order than the other two, and thus is most stable. Then, a further study on the electrical potential surfaces (EPS) proves that the stability of boat conformation can be contributed to the better balance between the positive and negative EPS. Next, according to molecular energy gap and density of state, the effect of each group on molecule is investigated: electrons on nitro group, compared with those on the framework, are easier to be activated so as to cause decomposition, thus nitro groups will determine the stability of molecule. Finally, the explosive velocity, pressure, and impact sensitivity of designed compounds are calculated. Results show that their explosive performances are significantly better than current energetic materials, and it is extraordinary enough that some compounds among them also maintain very good sensitivity.

Peramivir is a potent neuraminidase (NA) inhibitor for treatment of influenza infection by intravenous administration. By replacing the carboxylate group in peramivir with a phosphonate group, phosphono-peramivir (6a), the dehydration and deoxy derivatives (7a and 8a) as well as their corresponding monoalkyl esters are prepared from a pivotal intermediate epoxide 12. Among these phosphonate compounds, the dehydration derivative 7a that has a relatively rigid cyclopentene core structure exhibits the strongest inhibitory activity (IC50 = 0.3-4.1 nM) against several NAs of wild-type human and avian influenza viruses (H1N1, H3N2, H5N1, and H7N9), although the phosphonate congener 6a is unexpectedly less active than peramivir. The inferior binding affinity of 6a is attributable to the deviated orientations of its phosphonic acid and 3-pentyl groups in the NA active site as inferred from the NMR, X-ray diffraction, and molecular modeling analyses. Compound 7a is active to the oseltamivir-resistant H275Y strains of H1N1 and H5N1 viruses (IC50 = 73-86 nM). The phosphonate monoalkyl esters (6b, 6c, 7b, 7c, 8b, and 8c) are better anti-influenza agents (EC50 = 19-89 nM) than their corresponding phosphonic acids (EC50 = 50-343 nM) in protection of cells from the viral infection. The phosphonate monoalkyl esters are stable in buffer solutions (pH 2.0-7.4) and rabbit serum; furthermore, the alkyl group is possibly tuned to attain the desired pharmacokinetic properties.

A novel coordination polymer, {[Ni( bib ) 3 ](ClO 4 ) 2 } ∞ ( 1 ), was synthesized by the reaction of Ni(ClO 4 ) 2 ·6H 2 O with a linear rigid ligand 1,4-bis(imidazol-1-yl)benzene ( bib ). In this complex, the homoleptic octahedral nickel(II) node is connected by the rod-like spacer bib into an α-Po framework with larger pcu lattices, which are seemingly surrounded by double walls. The void space provided by the square-shaped channel is filled with another equivalent framework, i.e. complex 1 representing a unique interpenetrating α-Po topology network. Furthermore, magnetic study shows that there exists very weak antiferromagnetic exchange coupling in the complex.

Researches on the relation of a loaded mechanical energy to the damaged banana maturation and its quality evolution has significance to its storage, but there are few researches at present. This paper studied on the effect of the loaded energy on banana to its internal maturation substance evolution and stored quality with time, including the change of maximum impact stress, re-enduring impact energy. The results showed there existed a significant correlation between energy transformation and increment of maturity substance in the damaged banana. Also, there existed a significant association between energy transformation and increment of maturity substance in the damaged banana in its storage time, and appeared a trends that the mechanical energy being transferred into fruit internal energy increased its maturity substance and decreased its stored quality, but individual maturity difference had less effect. Thus, decreasing the energy and the substance transformation in damage area are the important means of extending the physiology life of fruits, which is an urgent problem to be solved in their field of processing and storage at present.

Mononitration of aromatics was performed in a two-phase system using phase-transfer catalyst. The most advantageous conditions for the nitration were determined (temperature, reaction time, the type and amount of phase transfer catalyst, nitrification strength of the nitro-sulfuric acid). From the results, a significant improvement in the selectivity and conversion of the nitration of xylene was observed: the ratio of 4-nitro-m-xylene to 2-nitro-m-xylene was unprecedented increased up to 91.3%:7.7%, the ratio of 4-nitro-o-xylene to 3-nitro-o-xylene was also increased to 71.1%:27.2%; both the conversions were over 96%.

Regioselective mononitration of simple aromatic compounds has been investigated with N2O5 as nitrating agent and a new PEG200-based dicationic acidic ionic liquid (PEG200-DAIL) as catalyst. The results of experiments show that this nitration system can significantly improve the para-selectivity of alkyl-benzenes and the ortho-selectivity of halogenated-benzenes. The PEG200-DAIL exhibits recyclable temperature-dependant phase behavior in CCl4 solvent, and it can be recycled without apparent loss of catalytic activity, and only 5% loss of weight is observed after six times recycling.

By the method of Density Functional Theory, at B3LYP/6-311G** level, works are done to optimize the charge distribution of nine kinds of aromatic groups. Meanwhile, the activation hardness is introduced and used to check the presented calculations' validity. Based on these studies, the orientation of electrophilic aromatic substitution is discussed. Experimental results show that the nitrification activity described with NBO net charge has a relationship with the nitrification strength, and it is an excellent index for predicting orientation effects.

Asimple, efficient, and environmentally friendly procedure for the amination of organic halides catalyzed by CuSO4·5H2 Oi n PEG1000-DIL/methylcyclohexane temperature-dependent biphasic system is described. The product can be easily isolated by a simple decantation, and the catalytic system can be recycled and reused without loss of catalytic activity.

As described in this article, 4,4′-bis(chloromethyl)biphenyl was obtained in 85% excellent yield by chloromethylation of biphenyl catalyzed by the recyclable temperature-dependant phase-separation system that comprised the dicationic acidic ionic liquid PEG1000-DAIL and methylcyclohexane under homogeneous catalysis in aqueous media. Compared to other synthetic methods, the novel method not only enhanced the yield, but also made the operating units easy workup. The mechanism of chloromethylation reaction and the process of catalysis in the thermoregulated ionic liquid bi-phase system were proposed.

A fibrous nanosized catalyst with TEMPO supported on silica nanospheres was synthesized and used in the selective oxidation of alcohols into the corresponding aldehydes or ketones. The fibrous morp...

Microsphere aluminum hypophosphite (AHP) is prepared via the hydrothermal method and characterized by Fourier transform infrared spectrometry, X-ray diffraction, and scanning electron microscopy. Then the hydrothermal AHP and the precipitation AHP are added to the polyurethane elastomer (PUE). The flame retardant properties, thermal stability, and mechanical properties of the PUE with different kinds of AHP added are studied. The results show that the hydrothermal AHP is microsphere with a uniform particle size of around 5 µm. The limited oxygen index of the PUE with the addition of 5% hydrothermal AHP increases to 28.5 vol %. Compared with the PUE including different kinds of AHP, the peak heat release rate of added hydrothermal AHP decreases by about 6%. Hydrothermal AHP could improve the char yield which provides better flame retardancy for PUE. Meanwhile, the hydrothermal AHP-added PUE has better mechanical properties than that with precipitation AHP added. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42370.

TEMPO supported on fibrous silica nanospheres is shown to be an efficient catalyst for the selective oxidation of (hetero)aromatic, aliphatic, allylic, and secondary alcohols.

A series of no-chlorine and oxygen-rich hydrazine derivatives (hydrazine modified with -NO₂ and NO₃(-) groups) was designed and optimized to obtain molecular geometries and electronic structures at density functional theory-B3PW91/6-311++G(3df,3pd) level. Some important properties such as bond dissociation enthalpy, density, natural bond orbitals, thermodynamic parameters, molecular orbital energy and burning rate were then calculated. The simulation results revealed that these compounds exhibit excellent performance, with significant superiority over traditional oxidants found in propellants.

Reaction of aromatic hydrocarbons catalyzed by a novel catalytic system consisting of zinc chloride, acetic acid, sulfuric acid and PEG-800 in aqueous media under PTC conditions results in chloromethylation in good to excellent yield.