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As phenol possesses a threat to human health, there is a great demand to search for fast and efficient methods for it to be discharged. In this study, a novel biomaterial was prepared by the immobilization of bacteria on a cationic straw carrier, and the remediation ability of the biomaterial on phenol-containing wastewater was investigated. The free bacteria could degrade 1,000 mg/L phenol within 240 h, while the prepared biomaterial was 192 h, shortening by 48 h that of free bacteria. In addition, the degradation tolerance of biomaterial increased from 1,000 mg/L to 1,200 mg/L than the free bacteria, within 216 h, which shortened by 24 h the degradation time of 1,000 mg/L phenol by free bacteria (240 h). Further, under different pH conditions, the degradation efficiency of phenol by prepared biomaterial was much higher than that of free bacteria. Especially for the lower pH 5, the degradation efficiency of biomaterial was nearly twice that of the free bacteria. This investigation demonstrates that this biomaterial has great potential in the field of remediation of organic pollution. HIGHLIGHTS A novel biomaterial was prepared by the fixation of bacteria on cationic straw.; The biomaterial can shorten the time and increase phenol concentration for degradation, compared to the free bacteria.; At a lower pH, the degradation efficiency of biomaterial is nearly twice that of the free bacteria.

OBJECTIVE This study aimed to observe the effect of glutamine (Gln) on brain damage in septic rats and explore its possible mechanism. METHODS Ninety-three Sprague-Dawley rats were randomly divided into five groups: sham operation group, sepsis group, Gln-treated group, quercetin/Gln-treated group, and alloxan/Gln-treated group. The rats in each group were continuously monitored for mean arterial pressure (MAP) and heart rate changes for 16 h. Neuroreflex scores were measured 24 h after surgery. The water content of the brain tissue was measured. Plasma neuron enolase and cysteine protease-3 were measured using the ELISA. The expression levels of heat shock protein 70 (HSP70) and oxygen-N-acetylglucosamine (O-GlcNAc) were determined by western blot analysis. Finally, the brain tissue was observed via hematoxylin and eosin staining. RESULTS The brain tissue water content, plasma neuron enolase content, brain tissue cysteine protease-3 content, and nerve reflex score were significantly lower in the Gln-treated group than in the sepsis group (P < 0.05). At the same time, the pathological brain tissue damage in the Gln-treated group was also significantly reduced. It is worth noting that the expression of HSP70 and the protein O-GlcNAc modification levels in the Gln-treated group were significantly elevated than the levels in the sepsis group (P < 0.05), and reversed by pretreatment with the HSP and O-GlcNAc inhibitors quercetion and alloxan. CONCLUSIONS Gln can attenuate brain damage in rats with sepsis, which may be associated with increased protein O-GlcNAc modification.

Epilepsy is one of the most common diseases of the nervous system. Neuronal apoptosis is closely involved in the development and progression of epilepsy. Triptolide is a widely used immunosuppressive agent in traditional Chinese medicine. However, a neuroprotective role of triptolide in epilepsy has been suggested but not fully explored. To this end, using pentylenetetrazol-induced seizures in rats as a model for epilepsy, we explored the effect of triptolide on seizure and its associated mechanisms. The results showed that triptolide significantly decreased the seizure severity and inhibited the apoptosis of neurons, accompanied by an improvement in the expression of miR-187 in the hippocampus region in pentylenetetrazol-treated rats. The up-regulation of miR-187 expression could inhibit neuronal apoptosis in the hippocampus. Finally, the results showed that miR-187 antagomir significantly reversed the protective effects of triptolide in pentylenetetrazol-treated rats. To the best of our knowledge, this is the first study demonstrating that triptolide inhibits neuronal apoptosis, at least partially, through up-regulating miR-187.

This paper reports host-guest inclusion systems of mangiferin (MGF) with four polyamine-modified β-cyclodextrins (PAβCDs). The inclusion complexes have been characterized by 1D and 2D nuclear magnetic resonance (NMR), thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The results show that MGF was encapsulated into the cavities of PAβCDs to form four complexes with 1:1 stoichiometry. The water solubility of the complexes was enhanced markedly, and the cytotoxicity of these complexes to normal cell line HEK293 was significantly reduced in comparison with native MGF. This satisfactory water solubilization and improvement of cytotoxicity with MGF/PAβCDs complexes will be potentially useful for its application as herbal medicine or healthcare products.

A validated high-performance liquid chromatography (HPLC) method has been developed to analyze the (±)-gossypol in the selection of strains of Candida tropicalis culture. Since gossypol was easily degraded and oxidized, the addition of antioxidant NADPH-Na4 and acetone extraction was chosen to prevent gossypol degradation and gradient elution assay was applied to obtain gossypol resolution. Concentrations of gossypol in C. tropicalis ZD-3 culture 20 μg/mL were determined, and concentration–time profiles were observed. Linearity of the gossypol standard curve by HPLC area method was ranged from 0.1 to 20 μg/mL with Y = 26.954 × X − 29.547, R2 = 0.9991, and n = 3, with limit of detection (LOD) of 50 ng/mL and lower limit of quantification (LLOQ) of 500 ng/mL. The recovery rate is dose-dependent and ranged from 85.3% to 103.5%. It is a rapid and reliable HPLC method for gossypol quantization in microorganism culture which could be applied in solid fermentation in the feed industry.

Background Our aim was to investigate the effects of the protein expression and the function of sodium, potassium, and chloride co-transporter (NKCC1) in the dorsal root ganglion (DRG) after activation of transient receptor potential vanilloid 1 receptor (TRPV1) in capsaicin-induced acute inflammatory pain and the possible mechanism of action.Methods Male Sprague–Dawley rats were randomly divided into control, capsaicin, and inhibitor groups. The expression and distribution of TRPV1 and NKCC1 in rat DRG were observed by immunofluorescence. Thermal radiation and acetone test were used to detect the pain threshold of heat and cold noxious stimulation in each group. The expressions of NKCC1 mRNA, NKCC1 protein, and p-NKCC1 in the DRG were detected by PCR and western blotting (WB). Patch clamp and chloride fluorescent probe were used to observe the changes of GABA activation current and intracellular chloride concentration. After intrathecal injection of protein kinase C (PKC) inhibitor (GF109203X) or MEK/extracellular signal-regulated kinase (ERK) inhibitor (U0126), the behavioral changes and the expression of NKCC1 and p-ERK protein in L4–6 DRG were observed.Result: TRPV1 and NKCC1 were co-expressed in the DRG. Compared with the control group, the immunofluorescence intensity of NKCC1 and p-NKCC1 in the capsaicin group was significantly higher, and the expression of NKCC1 in the nuclear membrane was significantly higher than that in the control group. The expression of NKCC1 mRNA and protein of NKCC1 and p-NKCC1 in the capsaicin group were higher than those in the control group. After capsaicin injection, GF109203X inhibited the protein expression of NKCC1 and p-ERK, while U0126 inhibited the protein expression of NKCC1. In the capsaicin group, paw withdrawal thermal latency (WTL) was decreased, while cold withdrawal latency (CWL) was prolonged. Bumetanide, GF109203X, or U0126 could reverse the effect. GABA activation current significantly increased in the DRG cells of the capsaicin group, which could be reversed by bumetanide. The concentration of chloride in the DRG cells of the capsaicin group increased, but decreased after bumetanide, GF109203X, and U0126 were administered.Conclusion Activation of TRPV1 by exogenous agonists can increase the expression and function of NKCC1 protein in DRG, which is mediated by activation of PKC/p-ERK signaling pathway. These results suggest that DRG NKCC1 may participate in the inflammatory pain induced by TRPV1.

We have developed a cyanide-free strategy for the synthesis of glycosyl carboxylic acids, which can provide 1,2-trans or 1,2-cis glycosyl carboxylic acids and is compatible with common protecting g...

Supramolecular encapsulation, which removes harmful substances from organisms, has evolved into a new strategy. In this paper, three supramolecular complexes of acyclic cucurbit[n]urils (ACBs) with uric acid (UA) were prepared, and the inclusion behavior of ACBs and UA was studied by fluorescence spectroscopy, UV–vis spectroscopy and nuclear magnetic resonance. Furthermore, the effect of the complexes of UA with ACBs on the expression of inflammatory biomarkers in human hepatoma HepG2 cell lines was characterized through C-reactive protein (CRP) western blot. The results showed UA molecules can be recognized by three ACBs with different binding constants, and ACBs successfully blocked the inflammatory stimulation of UA on HepG2 cell lines and inhibited the expression of the major inflammatory factor CRP by the formation of complexes between UA and ACBs. This article proves that ACBs can efficiently reverse the cytotoxicity of UA, which provides a new method for treating hyperuricemia disease.

In this paper, the volatile flavour constituents and the bacterial diversity in characteristic Chinese fermented sour soup were analysed, and the dynamics of bacteria associated with the odour were characterized. The bacterial diversity of sour soup was studied by high-throughput sequencing. A total of 10 phyla and 89 genera were detected. Firmicutes was the dominant phylum of sour soup, accounting for 87.14&ndash, 98.57%. The genus structure of normal sour soup was relatively simple, and Lactobacillus (78.05&ndash, 90.26%) was the dominant genus. In addition to Lactobacillus, the foul-smelling sour soup contained more Pediococcus spp., Caproiciproducens spp., and Clostridium-sensu-stricto12 spp. (relative abundance &gt, 1%) than the normal sour soup. A total of 51 aroma compounds were detected by gas chromatography-mass spectrometry(GC-IMS), including 25 esters, 8 terpenes, 8 alcohols, 3 sulfur compounds, 2 acids, 2 ketones, 1 pyrazine, 1 monoterpene and 1 aldehyde. According to the relative odour active value (ROAV) calculation, 51 important flavour-contributing substances and 7 flavour-coordinating substances were determined. The esters with the highest relative percentages and ROAV values provided the pleasant flavour of the sour soup. In the foul-smelling sour soup, the ROAV values of 1,8-cineole, isobutyl acetate, ethyl butanoate, ethyl octanoate-M, and ethyl hexanoate-M decreased, while those of diallyl disulfide-M and diallyl disulfide-D, which were probably responsible for the foul flavour, increased. Through Pearson correlation analysis, the odour production of the foul-smelling soup was determined to be related to Pediococcus spp., Caproiciproducens spp., Clostridiumsensu_stricto_12 spp., Oscillibacter spp., Bacteroides spp., Fibaculaceae_unclassified spp., Acinetobacter spp. and Halomonas spp.

A cost-effective, simple, and time-saving method to fabricate mono-dispersed periodic microsphere structures on substrates with patterned sites is very meaningful due to their significance on various biological studies. Herein, a simple and facile method to fabricate mono-dispersed microsphere arrays on porous substrates was developed. The mixture of polystyrene and an organic stabilizer solution which contains aqueous solution, fabricated through shaking, was applied to prepare microemulsion solution. An ordered porous structure was produced by spreading and evaporating the solvent of microemulsion on a glass slide, accompanied by the enrichment of didodecylamine in the cavities. The porous cavities were further modified with polyacrylic acid and poly(diallyldimethylammonium chloride) which could immobilize the microspheres. The charged microspheres were incorporated into the cavities by an electrostatic interaction with the oppositely charged polyelectrolytes. The positive polyelectrolytes with abundant charges as well as a suitable content and dimension of microspheres, ensured the formation of mono-dispersed and ordered arrays. Considering that other charged particles were universally suitable for the present strategy, the reported approach opened an efficient way for the preparation of microsphere-based materials.

Five polysaccharide fractions (PS-1, PS-2, PS-3, PS-4 and PS-5) were successfully isolated from Athyrium Multidentatum (Doll.) Ching by anion-exchange column chromatography. Their in vitro cytoprotective activities and the underlying mechanisms were explored in this paper. Chemical analysis suggested that the five polysaccharide fractions were heteropolysaccharides with different molecular weights and monosaccharide compositions. Treatment with these polysaccharide fractions could increase cell viabilities, superoxide dismutase/catalase activities, nitric oxide contents, mitochondrial membrane potential levels and Bcl-2/Bax ratios, and reduce cell apoptosis, intracellular reactive oxygen species production and malondialdehyde contents in H2O2-damaged cells. Moreover, these polysaccharide fractions enhanced the mRNA expression levels of PI3K, Akt, FOXO3a, Nrf2 and HO-1 and PS-4 exhibited the most powerful effects on the mRNA expression of these genes. Current findings suggested that the polysaccharide fractions decreased H2O2-induced apoptosis of HUVECs. The activation of PI3K/Akt/FOXO3a and Nrf2/HO-1 signaling pathways might be involved in the protective mechanisms of the active fractions. The polysaccharides might be one of the key bioactive ingredients of Athyrium Multidentatum (Doll.) Ching for the treatment of oxidative damage.

The purpose of this study was to develop a novel folate-modified host-guest complex to enhance antitumor activity of the artesunate and improve the solubility and stability by encapsulated in β-cyclodextrin and linked with folate. In this work, we designed and prepared the inclusion complex of adamantanamine conjugated artesunate (AD-ATS) with folic acid-ethylenediamine-β-cyclodextrin (FA-EN-β-CD). This material was characterized by 1D and 2D NMR, XRD, TG and SEM. The results suggested that AD-ATS was encapsulated within the FA-EN-β-CD cavity to form host-guest inclusion complex, and the water solubility of AD-ATS was improved in the form of inclusion complex with FA-EN-β-CD. The assessment of antitumor activity showed that cytotoxicity of AD-ATS/FA-EN-β-CD complex was significantly enhanced in comparison to free AD-ATS, ATS/β-CD inclusion complex and ATS/FA-EN-β-CD inclusion complex.

A simple and facile method to fabricate porous films which were locally patterned by heteropoly acid was developed in this study. The mixture of poly(methyl methacrylate) and stabilizer dichloromethane solution which contains heteropoly acid aqueous solution, prepared through shaking, was applied to fabricate a reversed microemulsion. After spreading and evaporating the solvent of microemulsion on a glass slide, an ordered honeycomb film was produced by incorporation of heteropoly acid in the cavities. The locally anchored heteropoly acid could be readily applied for the selective modification of the porous films through the in situ chemical reactions in the cavities with the additive agents. The silver nanoparticles were in situ prepared via the reduction of silver ions by reduced state H3PW12O40, and the polypyrrole spheres were locally obtained through the oxidative polymerization of pyrrole catalyzed by H3PMo12O40 in the cavities. Considering that water-soluble molecules and nanoparticles were universally suitable for the present strategy, the reported approach opened up an efficient way for patterning organically incompatible components on porous polymer films via the assembly of microemulsion droplet carriers to fabricate multi-functional hybrid surface structures.

This study shed light on removing atrazine from pesticide production wastewater using a pilot-scale UV/O3/ultrasound flow-through system. A significant quadratic polynomial prediction model with an adjusted R2 of 0.90 was obtained from central composite design with response surface methodology. The optimal atrazine removal rate (97.68%) was obtained at the conditions of 75 W UV power, 10.75 g h−1 O3 flow rate and 142.5 W ultrasound power. A Monte Carlo simulation aided artificial neural networks model was further developed to quantify the importance of O3 flow rate (40%), UV power (30%) and ultrasound power (30%). Their individual and interaction effects were also discussed in terms of reaction kinetics. UV and ultrasound could both enhance the decomposition of O3 and promote hydroxyl radical (OH·) formation. Nonetheless, the dose of O3 was the dominant factor and must be optimized because excess O3 can react with OH·, thereby reducing the rate of atrazine degradation. The presence of other organic compounds in the background matrix appreciably inhibited the degradation of atrazine, while the effects of Cl−, CO32− and HCO3− were comparatively negligible. It was concluded that the optimization of system performance using response surface methodology and neural networks would be beneficial for scaling up the treatment by UV/O3/ultrasound at industrial level.

Transitional metal chalcogenides with remarkable electrochemical performance are recently attracted growing interest as a novel type of material in the field of energy storage. Herein, neoteric hollow nanoscale tubular x-MnS/Co3S4 (x = 25, 50, 100, 200, 400) hybrids are achieved by two steps of ion exchange methods applying self-made cobalt chloride carbonate hydroxide (Co(CO3)0.35Cl0.20(OH)1.10) as precursor, sodium sulfide nonahydrate as a sulfur resource for anion exchange, and anhydrous manganese chloride as a manganese resource for cation exchange. When used in supercapacitors for the first time, the 200-MnS/Co3S4 sample manifests excellent electrochemical performance with high specific capacitance (627 Fg−1 at 1 A g − 1), exceptional rate capability (73.5% capacity retention from 1 to 50 A g − 1), and brilliant cycling stability (93.1% of initial capacity retention for 2000 cycles at 10 A g − 1). These results above indicate the great potential of hollow MnS/Co3S4 nano-tubes in the development of high-performance electrode materials for supercapacitors.

In this study, a stable and sensitive acetylcholinesterase biosensor was developed for the electrochemical determination of 3-nitropropionic acid (3-NPA). To this end, NaOH etching was used to activate the surface of the glassy carbon electrode, and the morphologies and electrochemistry properties of the resulting electrodes were characterized by various analytical methods. The results indicated dramatic enhancement in the electrochemical properties of electrodes by NaOH etching. As a result, the etched electrodes were applied as novel platforms for the immobilization of acetylcholinesterase. Accordingly, a sensor based on inhibition of 3-NPA toward the activity of acetylcholinesterase was constructed for the electrochemical determination of 3-NPA. Under the optimal conditions, the inhibition rate was found to be proportional to the logarithm of the concentration of 3-NPA from 0.1 to 30 μg/L, and the limit of detection was recorded as 0.05 μg/L. In comparison to conventional detection method, the fabricated biosensor also has added advantages in the form of easy and convenient operation, high sensitivity and better linear range.

In this study, a UV/O3 hybrid advanced oxidation system was used to remove chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and atrazine (ATZ) from ATZ production wastewater. The removal of COD and NH3-N, under different UV and O3 conditions, was found to follow pseudo-first-order kinetics with rate constants ranging from 0.0001–0.0048 and 0.0015–0.0056 min−1, respectively. The removal efficiency of ATZ was over 95% after 180 min treatment, regardless the level of UV power. A kinetic model was further proposed to simulate the removal processes and to quantify the individual roles and contributions of photolysis, direct O3 oxidation, and hydroxyl radical (OH·) induced oxidation. The experimental and kinetic modeling results agreed reasonably well with deviations of 12.2 and 13.1% for the removal of COD and NH3-N, respectively. Photolysis contributed appreciably to the degradation of ATZ, while OH· played a dominant role for the removal of both COD and NH3-N, especially in alkaline environments. This study provides insights into the treatment of ATZ containing wastewater using UV/O3 and broadens the knowledge of kinetics of ozone-based advanced oxidation processes.

To simulate the Pt/C agglomerate phenomenon in proton exchange membrane fuel cell (PEMFC) cathode, we established 3D two-phase micro-structure lattice models, including C phase (Pt/C particles) and IP phase (mixed ionomer and pore), respectively. Based on these models, we studied the effect of Pt/C agglomerates on theoretical catalyst utilization, IP phase tortuosity and cell performance in PEMFC, and compared the electrode with linear agglomerates to the electrode with spherical agglomerates. Unexpectedly, contrary to the simulation results from macro-models, the electrode with Pt/C linear agglomerates performed better than that with Pt/C spherical agglomerates. In addition, it was found that the electrode with Pt/C agglomerates performed better than that without Pt/C agglomerates, which was different to what we believed before. By analysing the reasons of cell performance change, it was found that mass transport had a more important effect on cell performance than electrochemical reaction.

Flos Chrysanthemi indici, an important medicinal and aromatic plant in China, is considered to have many different preservative and pharmacological properties. Considering the capability of essential oils (EOs), the present study is conducted to compare different extraction methods in order to improve yield and biological activities. Hydro-distillation (HD), steam-distillation (SD), solvent-free microwave extraction (SFME), and supercritical fluid extraction (SFE) are employed to prepare EOs from Flos Chrysanthemi indici. A total of 71 compounds are assigned by gas chromatography/mass spectrometry (GC&ndash, MS) in comparison with retention indices. These include 32 (HD), 16 (SD), 31 (SFME) and 38 (SFE) compounds. Major constituents of EOs differ according to the extraction methods were heptenol, tricosane, camphor, borneol, and eucalyptol. EOs extracted by SFME exhibit higher antioxidant activity. All EOs show varying degrees of antimicrobial activity, with minimum inhibitory concentration (MIC) ranging from 0.0625 to 0.125 mg/mL and SFME and SFE prove to be efficient extraction methods. EOs alter the hyphal morphology of Alternaria alternata, with visible bumps forming on the mycelium. Overall, these results indicate that the extraction method can significantly influence the composition and biological activity of EOs and SFME and SFE are outstanding methods to extract EOs with high yield and antimicrobial activity.

In this study, five growth stages of Oriental lily ‘Justina’ leaves (10 d, 25 d, 50 d, 75 d and 100 d), and seven different parts of styles, anthers, petals, leaves, stems, bulbs and roots in 100 day growth were used as test materials to measure the content of carotenoid and chlorophyll in Lilium by organic solvent method. The semi-quantitative expression analysis of 12 key enzyme genes ( PSY , PDS , Z-ISO , ZDS , CRTISO , LCYB , LCYE , HYB , VDE , ZEP , CCS and NCED ) of Lilium carotenoid metabolic pathway was carried out according to the sequencing results of transcriptome library. The study cloned the open reading frame (ORF) sequence of Lilium LCYB gene and carried out related bioinformatics analysis. The results showed that carotenoid and chlorophyll content were significantly different in the five different stages of Lilium leaf growth and seven different parts of Lilium ripening stage. The expression levels of 12 key enzyme genes were variant in different growth stages and parts. The complete ORF of the LCYB gene was cloned with the whole length of 1,503 bp, encoding 500 amino acids, which had typical conserved region characteristics of Carotene Cycl super family. It showed the closest relationship with Musa acuminata among the known genome-wide plants. This study might provide a solid theoretical basis for further study of Lilium carotenoid metabolic pathways and further understanding of the molecular mechanism of Lilium color and leaf color synthesis.

In order to increase the applicability of photocatalysis in treating offshore produced water (OPW), an immobilized catalyst was introduced into the UV irradiation system and its performance on the degradation of organic compounds in OPW was evaluated. Naphthalene was selected as the target pollutant owing to its abundance in produced water and its chemical property as a typical polycyclic aromatic hydrocarbon. Aeroxide ® P25 nano-scale TiO 2 powder was immobilized on glass slides by a heat attachment method and its photocatalytic capacity was compared to that of the original powder in terms of naphthalene removal efficiency. The results of adsorption showed that the reduction of catalysts’ surface area by immobilization was similar to that by agglomeration. The photocatalytic reaction rate constants in the homogeneous and immobilized systems were 0.00219 min −1 and 0.00305 min −1 , respectively, indicating that the immobilized catalyst had a better performance in photo-oxidation. The fouling of catalyst surface during the irradiation process came from the deposition of insoluble particles, organic matters, and the scaling of calcium. In summary, the immobilization of catalysts was more resistant to the substrate effects of OPW, indicating a more promising alternative in treating OPW.

The novel 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by thiophene ring closure. The first step is the synthesis of S-alkylated derivatives by the reaction of 6-substituted-2-thiouracils with the appropriate substituted phenacyl halides. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 3-(substituted phenyl)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to the corresponding sulfonic acid derivatives occurred. Further, acylation of the 7-NH2 group of 5H-thiazolo[3,2-a]pyrimidin-5-ones afforded amide derivatives, and reduction of the NO2 group of 5H-thiazolo[3,2-a]pyrimidin-5-ones gave amino derivatives. All the new compounds were confirmed by 1H NMR, 13C NMR, IR and HRMS spectra, and their antibacterial and antitubercular activities were screened. Some compounds showed significant antibacterial and antitubercular activities.

Background: In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in FVC over 52 weeks vs placebo, with no difference between groups in change in mRSS. Objectives: Analyse correlation between progression of skin fibrosis and progression of SSc-ILD in the SENSCIS trial. Methods: Patients with SSc-ILD were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤100 weeks. We calculated Spearman correlation coefficients between FVC (mL) at baseline and change from baseline in mRSS, mRSS at baseline and change from baseline in FVC (mL), and changes from baseline in mRSS and FVC at weeks 52 and 100 in all patients. We analysed the rate of decline in FVC (mL/year) in patients who did and did not have progression of skin fibrosis (relative change from baseline in mRSS >25% and absolute change from baseline >5 points) at week 52. Results: In the nintedanib (n=288) and placebo (n=288) groups, respectively, mean (SD) baseline FVC (mL) was 2459 (736) and 2541 (816) and mRSS was 11.3 (9.2) and 10.9 (8.8); 53.1% and 50.7% had dcSSc;18.4% and 16.0% had progression of mRSS at week 52. No meaningful correlations were observed in analyses between mRSS and FVC (Table). The mean (SE) annual rate of decline in FVC in the placebo group was similar in patients who did and did not have progression of mRSS (-95.2 [27.1] and -91.4 [15.7] mL/year, respectively). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in patients who did not have progression of mRSS vs those who did (difference [95% CI] 44.3 mL/year [0.6, 88.1] vs 24.6 [-53.7, 102.9]), but the interaction p-value (0.66) did not indicate heterogeneity in treatment effect between subgroups. Conclusion: In the SENSCIS trial, the proportion of patients who had progression of skin fibrosis over 52 weeks was low, without significant differences between placebo and nintedanib. No meaningful correlations were observed between skin fibrosis at baseline or progression of skin fibrosis and progression of SSc-ILD. The rate of decline in FVC was similar between patients who did and did not have progression of mRSS. These findings suggest that in the overall patient population in the SENSCIS trial, progression of skin fibrosis and progression of ILD were distinct manifestations of disease progression. Disclosure of Interests: Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Kristin Highland Grant/research support from: Boehringer Ingelheim - PI for SENSCIS and SENSCIS-ON trials (paid to my institution), Consultant of: Kristin Highland has acted as a consultant to Boehringer Ingelheim. She was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Speakers bureau: Kristin Highland reports speaker fees from Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Otylia Kowal-Bielecka Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Inventiva, MSD, Novartis, Speakers bureau: Boehringer Ingelheim, Medac, Novartis, Roche, Sandoz, Ulrich Walker Grant/research support from: Ulrich Walker has received an unrestricted research grant from Abbvie, Consultant of: Ulrich Walker has act as a consultant for Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, Sanofi, and ThermoFisher, Paid instructor for: Abbvie, Novartis, and Roche, Speakers bureau: Abbvie, Actelion, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, and ThermoFisher, Francesco Del Galdo: None declared, Madelon Vonk Grant/research support from: Janssen and Ferrer, Consultant of: Boehringer Ingelheim, Janssen and GSK, Speakers bureau: Boehringer Ingelheim, BMS and Roche, Laura Hummers Grant/research support from: Boehringer Ingleheim, Corbus pharmaceuticals, CSL Behring, Cumberland Pharmaceuticals, and GlaxoSmithKline, Consultant of: Boehringer Ingleheim, Corbus pharmaceuticals, and CSL Behring, Elvira Erhardt Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Incorporating bioaccessibility into human health risk assessment is recognized as a valid way to reduce the conservative properties of conventional results, where the total concentration of a contaminant analysed by exhaustive chemical extraction is applied. Taking a coke production site in Beijing as an example, a mild chemical extraction technology was employed to profile the bioaccessibility of benzo[a]pyrene (BaP), indeno[1,2,3-cd]pyrene (IcP) and dibenz[ah]anthracene (DBA) in soils. The results that were regressed using two bi-phase desorption models (Karickhoff and Weibull) revealed that the rapid desorption fractions of BaP, IcP and DBA, which are taken for bioaccessible fractions, were basically less than half of the total contents in the soils. Probabilistic analysis (PA) was carried out with pre-set distributions of the exposure parameters to characterize the uncertainty in the assessment. The results incorporating bioaccessibility and PA were several times higher than the generic remediation goals which equal to national screening levels, and orders of magnitude higher than the baselines of the region and nation. The results of the Weibull fit were finally recommended as site-specific remediation goals (SSRGs) (10.59 mg/kg, 95.48 mg/kg and 9.24 mg/kg). Over-remediation was avoided while contributing to considerable economic and environmental benefits.

A simple and cheap method to fabricate a nanocrystal ring pattern was developed by utilization of a microemulsion in this study. The mixture of polystyrene and stabilizer dichloromethane solution that contained nanocrystal aqueous solution, prepared through shaking, was applied to fabricate a reverse microemulsion. After spreading and evaporating the solvent of microemulsion on a glass slide, an ordered honeycomb film was produced, accompanied by the formation of a nanocrystal ring pattern. The nanocrystal pattern could be readily applied for immunoassays and recognition of proteins. The pattern with antibody marked by a green colored nanocrystal specifically bound with antigen labeled by a red colored nanocrystal, leading to the enhancement in red fluorescent ring pattern and decrease in green fluorescent pattern. When the unlabeled antigen was added, the green fluorescent pattern was recovered. In addition, the ring pattern with immunocomplex could selectively recognize antigen and transferrin proteins. This strategy reveals that these patterns have potential applications in biochips, biosensors, imaging analysis and so forth.

The chronic discharge of marine oily wastewater, mainly including bilge water, offshore produced water and ballast water, has been referred to as a major contributor to marine oil pollution. Its unregulated discharge may cause serious, long-term damage to local industries such as fishery and tourism, coastal communities, and the environment. Petroleum hydrocarbons, organic acids, heavy metals, radionuclides, production chemicals, and many other contaminants in oily wastewater have led to the adoption of stringent regional, national, and international environmental standards, regulations, and management practices. To date, onboard treatment has been most often used to remove unwanted substances from oily wastewater. A number of physical, chemical, and biological methods, such as gravity separation, air flotation, coagulation, membrane filtration, absorption, adsorption, and biological treatment have been investigated. However, they are either ineffective on dispersed/free oil or not applicable for onboard treatment due to safety, space and cost concerns. Particularly, many dissolved organics such as polycyclic aromatic hydrocarbons (PAHs) may stay unaffected and raise serious environmental concerns. UV and advanced oxidation processes, on the other hand, have been gaining significant attention because of their small footprint, ability of complete mineralization of contaminants, ease of operation, low cost and risk, and high efficiency. However, as emerging technologies, the lack of understanding of reaction mechanisms and performance prediction in the marine environment may affect their applicability.

In this study, Bacillus thuringiensis (Bt) biopesticide was produced through different fermentation processes using food waste with different water contents. The semi-solid state sample with 75% water content presented the highest δ-endotoxin efficiency of 862 μg/mL. δ-endotoxin efficiency increased by 30.2% from that of the solid-state sample (50% water content) and 73.8% from that of the submerged sample (99% water content). Results confirmed that semi-solid state fermentation presents considerable advantages compared with other fermentation types (solid-state and submerged). The timing adjustment of pH and recycling fermentation effectively counteracted the inhibition of pH and product, thereby increasing δ- endotoxin efficiency to 1,648 and 2,478 μg/mL (accumulated value of all four fermentation loops), respectively. A δ- endotoxin slow-release formulation using polylactic acid as the carrier was also developed to effectively promote the stability of Bt biopesticide.

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. Key findings: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. Conclusion: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.

Ozonation has been recently proposed as a treatment option to remove toxic and recalcitrant organics from offshore produced water (OPW). In this study, experimental and modeling approaches were used to investigate the removal of polycyclic aromatic hydrocarbons (PAHs) from OPW by ozonation. It was found that ozonation can effectively remove PAHs by following the pseudo first-order kinetic model, which could cover both direct and indirect ozonation pathways. The decay rate constants of most PAHs were as low as 0.01–0.16 min−1, possibly due to the interference caused by OPW matrix. The effects of ozone dose, bubble size, pH, and temperature on five representative PAHs were investigated along with their possible interactions. Based on the experimental results, a novel multi-output adaptive network-based fuzzy inference system (MO-ANFIS) was developed to model the removal of four individual PAHs and total PAHs. The overall RMSE and R between measured and modeled removal rates were 6.60% and 0.98, respectively, indicating a good model fit. This study demonstrated the effectiveness of ozonation in OPW treatment and the potential applicability of MO-ANFIS for process modeling and control.

The solubilization of methylene blue (MB) in sodium dodecyl sulfate (SDS) using hollow fiber membrane was studied. In MEUF, the effects of important factors (MB and SDS concentrations, temperature and electrolyte concentration) on the permeate and retentate concentrations of MB and SDS, equilibrium distribution constant (Kd) and micelle loading (Lm) were investigated. It was found that MB molecules could be solubilized fully within micelles of SDS. The increase of feed SDS concentration promoted retentate MB concentration. Temperature could change the SDS micellization effect. The addition of NaCl could improve the retentate MB and SDS concentrations and reduce significantly the permeate SDS concentration.

article i nfo Article history: In this study, micellar-enhanced ultrafiltration (MEUF) was used to remove Cd 2+ from synthetic wastewater using a polysulfone spiral wound ultrafiltration membrane and sodium dodecyl sulfate (SDS) as a surfactant. The effects of two important parameters related to membrane fouling in MEUF were investigated: transmem- brane pressure (TMP) and feed concentration. The recycling of retentate to the feed tank, which led to con- tinuous growth of SDS concentration, is investigated. The permeate flux and fouling resistance around the critical micelle concentration (CMC) showed that higher SDS concentrations did not always lead to more se- rious fouling, but fouling became more serious after the SDS concentration reached five times the CMC. With increasing TMP, the flux declined drastically as a result of particle aggregation and gel layer formation. How- ever, the TMP was not always a good criterion of membrane fouling: in different phases, high TMP and low TMP values affected membrane fouling differently; a high TMP such as 0.25 MPa resulted in low membrane fouling at the beginning of the MEUF because of the higher driving power; and a low TMP such as 0.05 MPa caused more serious membrane fouling after stopping because of pore blocking.

The pollution soil from tar workshop’s foundation soil in a steel work, first of all, the main organic pollutants in pollution soil are examined by the Pony Test Center. Then, the volatility of the pollution soil at different temperature was studied by thermo gravimetric (TG) analysis coupled with Fourier transform infrared spectroscopy (FTIR). At last, by adding standard reagents of PAHs respectively, their volatility of different temperature period was confirmed. The results indicated that the main organic pollutants in the contaminated soil were fluorene, acenaphthene, phenanthrene, fluoranthene, pyrene and so on, the total content is about 156.39ppm. the weight loss of pollution soil mainly occurred at the temperature ranges of room temperature to 215°C, 215~670°C and 670°C~850°C. There were H2O and CO2 coupled with the weight loss. When temperature increased further up to and above 850°C, the weight tended to be stable. The volatilization of PAHs is mainly in the section of 215~670°C, and their fastest volatilized temperatures in pollution soil were lower about 30°C than their respective boiling points.

Micellar-enhanced ultrafiltration (MEUF) is a promising technology to remove metal ions and organic contaminants simultaneously from wastewater. A laboratory experiment was conducted to evaluate the efficiency of a MEUF operation for the removal of Cd2+ and phenol using pure SDS and mixed surfactants (Triton X-100/SDS). In pure SDS system, with the increase of the feed SDS concentration, a significant rise in Cd2+ rejection was obtained, which peaked at 97.0% with initial SDS concentration being 8.0 mM. Nevertheless, the phenol rejections only kept moderately increasing from 14.5% to 40.0%. In mixed Triton X-100/SDS system, the rejections of Cd2+ and phenol were both enhanced by the moderate addition of nonionic surfactant for the same total feed surfactant concentration as the pure SDS system. With the increase of the molar ratios of Triton X-100 to SDS (α), Cd2+ rejection increased slightly with α ranging from 0 to 0.8, and peaked at 91.3%. And the phenol rejection kept increasing from 27.7% to 42.4% when α was less than 1.0 followed by slight decrease to 40.2% at α = 1.5. Moreover, the SDS dosage and the surfactant(s) concentration in permeate were reduced efficiently. The permeate flux of MEUF with mixed surfactants was lower than that with pure SDS.

A rapid capillary zone electrophoresis (CZE) method with ephedrine hydrochloride as an internal standard was developed and validated for separating and quantifying the alkaloids strychnine (1), brucine (2), strychnine N-oxide (3), and brucine N-oxide (4) in the seed of Strychnos nux-vomica L. (crude nux vomica) and its fermented products by fungus Trametes cinnabarina (Jacq.: Fr.) Fr. (fermented nux vomica). The contents of alkaloids (1 and 2) in crude nux vomica were higher than those in fermented drugs, whereas alkaloids (3 and 4) were only detected in fermented ones. The method developed is sensitive, specific and accurate, as well as effective and easy, which can be used to assess the qualities of crude and fermented nux vomica.

Single and simultaneous removal of Cd(2+) and methylene blue (MB) with sodium dodecyl sulfate (SDS) by micellar-enhanced ultrafiltration under different experimental conditions was investigated. In single removal process, with initial SDS concentration increasing, the removal efficiency of Cd(2+) and MB kept increasing and then decreased. When the initial concentrations of SDS and Cd(2+) were 1.0 cmc and 50 mg L(-1), respectively, the maximum removal efficiency of Cd(2+) was obtained as 99.2%. Removal efficiency of MB could achieve more than 99.9% with initial SDS concentration below 2.0 cmc. As compared with single Cd(2+) removal, the removal efficiency of Cd(2+) in the presence of MB was slightly higher with initial SDS concentration below 1.0 cmc, while decreased with the SDS concentration above 1.0 cmc. The maximum removal efficiency of Cd(2+) was 98.8% when initial concentrations of SDS and MB were 1.0 cmc and 4 mg L(-1), respectively. The removal efficiency of MB in the presence of Cd(2+) could achieve higher than 96.5%, which was only 3.4% less than the optimum result of the single removal. Meanwhile, effect of pH on removal efficiency of Cd(2+) was more significant than that of MB.

Micellar-enhanced ultrafiltration (MEUF) of methylene blue (MB) from dye wastewater was explored for obtaining colorless water, using a 10-kDa molecular weight cut-off (MWCO) polysulfone hollow fiber membrane and sodium dodecylsulfate (SDS) as an anionic surfactant. The effects of factors, such as operating pressure, feed SDS, MB and sodium chloride (NaCl) concentrations, on the permeate flux (J) and additional resistance (Rf) as well as the observed MB and SDS rejection were investigated. Moreover, the zeta potential of SDS micelle with feed SDS, MB and NaCl concentrations in the solution was also quantified. The rejection of MB and SDS decreased slightly with operating pressure increasing. It was observed that the permeate flux decreased while the additional resistance increased with increased SDS and MB concentrations in the feed. The addition of NaCl significantly increased surfactant retention and reduced the back contamination. The rejection of MB and SDS were 99.3 and 96.0%, respectively, with MB (6 mg/L), SDS (8 mM) and NaCl (200 or 300 mM) in the solution.

Micellar-enhanced ultrafiltration (MEUF) is a powerful treatment developed to remove heavy metals from wastewater. Efficient removal of Cd(2+)/Zn(2+) from wastewater was performed by MEUF using a polysulfone hollow ultrafiltration membrane, with sodium dodecyl sulfate (SDS) as the surfactant. The adsorption of surfactant micelles and Cd(2+)/Zn(2+) in MEUF was studied by changing the surfactant dosage and the Cd(2+)/Zn(2+) concentration in the feed. In addition, kinetics, adsorption isotherms, and thermodynamic rules were analyzed, and X-ray photoelectron spectroscopy (XPS) was conducted. It was found that when the Cd(2+)/Zn(2+) feed concentration was 50 mg/L, and the SDS dosage reached 2.15 g/L, the concentration of heavy metal ions in the permeate stabilized at around 1-4 mg/L, and the adsorption of Cd(2+)/Zn(2+) on SDS micelles followed second-order kinetics and the Langmuir isotherm laws. Adsorption is a spontaneous endothermic process in which the adsorption force is principally the attraction of opposite electrical charges.

The mono-modified β-cyclodextrin derivative, 6-O-(4-aminobenzoyl)-β-cyclodextrin (1), was synthesized and characterized. We compared its self-assembling behavior with structurally related β-cyclodextrin derivative, 6-O-(4-hydroxybenzoyl)-β-cyclodextrin (2), in aqueous solution and in the solid state using NMR spectroscopy and single crystal X-ray structure analysis. The two complexes displayed different self-assembling behaviors. Complex 1 formed a head-to-tail helical columnar superstructure in which the substituent group penetrated deeply into the hydrophobic cavity of the adjacent β-cyclodextrin from the second side and aligned along the screw axis, whereas 2 exhibited a channel superstructure with a tail-to-tail dimer as the repeating motif. Further NMR studies in aqueous solution supported the result of the solid state. The influence of substituent groups on the self-assembly behavior was examined in mono-modified β-cyclodextrins by means of substituting an amino group for a hydroxyl group, which indicates that the weak intermolecular interaction is a critical factor in determining the self-assembling behavior.

The supramolecular self-assembly formed by newly synthesized mono-6-(4-cyano-phenyl)-β-cyclodextrin through the molecular interpenetration has been investigated and compared in both solution and the solid state, which was characterized by X-ray crystallography, fourier transform infrared spectroscopy, NMR spectroscopy and atomic force microscopy. The crystal structure clearly revealed that the benzonitrile group is consecutively inserted into the adjacent cyclodextrin cavity from the second side, thus giving rise to an unusual interlocked helical supramolecular self-assembly in which the benzonitrile group acts as bridge between the cyclodextrin units. As compared with crystal, the conformation in aqueous solution indicates that the benzonitrile group prefer to be self-assembled included into another cavity from the second side of cyclodextrin to form the self-assembly.

The inclusion complex (1) of with β-cyclodextrin-p-nitrophenoxyacetic acid was synthesized and characterized. Its inclusion behavior was investigated by means of X-ray crystallography and NMR spectroscopy in solution and in the solid state. The crystallographic study shows that one β-cyclodextrin co-crystallize with one p-nitrophenoxyacetic acid, and 17 water molecules in the Monoclinic system with unit cell constants: a = 18.6864(16), b = 24.961(2), c = 16.6644(14) A, β = 105.129(5)°. Two β-cyclodextrins are held together by hydrogen bonds to form head-to-head dimers. The disordered guest molecule molulates itself to attain the most stable accommodation into the cavity in which the nitro group is located at the dimer interface while the carboxyl group buried in the primary hydroxyl groups of β-CD. The further 2D NMR spectroscopy investigation in solution supports the inclusion mode of the solid state. The inclusion behavior of β-CD with p-NPOAA shows that β-CD forms a 1:1 complex with p-NPOAA, in which the nitro group of guest is located at the second hydroxyl groups and the carboxyl group is buried in the primary hydroxyl groups of β-CD.

The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair.

The mono-modified beta-cyclodextrin derivative, 6(I)-O-(3-nitrophenyl)cyclomaltoheptaose{mono[6-O-(3-nitrophenyl)]-beta-cyclodextrin} was synthesized, and its crystal structure was determined by single-crystal X-ray analysis. The crystal structure suggests that the 3-nitrophenyl substituent group is inserted into the adjacent beta-cyclodextrin cavity from the secondary hydroxyl side, and the molecules are stacked along the twofold screw axis to form an infinite one-dimensional polymeric chain.

Dysfunction of dopamine D4 receptor (D4R) is linked to attention-deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive impairment. Here, we tested the possible therapeutic benefit of the D4R-selective agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724-treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were injected with saline. Then two cohorts of rats were tested in the open field and Lat maze that measured locomotion and non-selective attention (NSA), respectively. Another cohort of rats was subjected to water maze task for evaluation of spatial learning and memory. We found that control SHRs displayed hyperactivity as well as impaired NSA and spatial learning compared with normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used as a therapeutic intervention for ADHD patients during adolescence.

In skeletal muscle both insulin and contractile activity are physiological stimuli for glycogen synthesis, which is thought to result in part from the dephosphorylation and activation of glycogen synthase (GS). PP1G/R(GL)(G(M)) is a glycogen/sarcoplasmic reticulum-associated type 1 phosphatase that was originally postulated to mediate insulin control of glycogen metabolism. However, we recently showed (Suzuki, Y., Lanner, C., Kim, J.-H., Vilardo, P. G., Zhang, H., Jie Yang, J., Cooper, L. D., Steele, M., Kennedy, A., Bock, C., Scrimgeour, A., Lawrence, J. C. Jr., L., and DePaoli-Roach, A. A. (2001) Mol. Cell. Biol. 21, 2683-2694) that insulin activates GS in muscle of R(GL)(G(M)) knockout (KO) mice similarly to the wild type (WT). To determine whether PP1G is involved in glycogen metabolism during muscle contractions, R(GL) KO and overexpressors (OE) were subjected to two models of contraction, in vivo treadmill running and in situ electrical stimulation. Both procedures resulted in a 2-fold increase in the GS -/+ glucose-6-P activity ratio in WT mice, but this response was completely absent in the KO mice. The KO mice, which also have a reduced GS activity associated with significantly reduced basal glycogen levels, exhibited impaired maximal exercise capacity, but contraction-induced activation of glucose transport was unaffected. The R(GL) OE mice are characterized by enhanced GS activity ratio and an approximately 3-4-fold increase in glycogen content in skeletal muscle. These animals were able to tolerate exercise normally. Stimulation of GS and glucose uptake following muscle contraction was not significantly different as compared with WT littermates. These results indicate that although PP1G/R(GL) is not necessary for activation of GS by insulin, it is essential for regulation of glycogen metabolism under basal conditions and in response to contractile activity, and may explain the reduced muscle glycogen content in the R(GL) KO mice, despite the normal insulin activation of GS.

In the title compound, C13H10N4O5·C3H7NO, the Schiff base is approximately planar. Molecules are connected via weak intermolecular O—H...O, N—H...O and C—H...O hydrogen bonds.

An inclusion complex formed by beta-cyclodextrin and quinine has been investigated in solution and in the solid state, in which the quinoline ring and the aliphatic ring locate in different hydrophobic cavities, respectively. The study on the inclusion geometry and weak interactions shows that the difference in conformation for this complex is a result of three main packing arrangement considerations, which can provide an ideal model mimicking enzyme-substrate interactions.