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Molecular chaperones Hsp90 and Hsp70 control many signal transducers, including cyclin-dependent kinases and steroid receptors. The yeast heme-responsive transcriptional activator Hap1 is a native substrate of both Hsp90 and Hsp70. Hsp90 and Hsp70 are critical for the precise regulation of Hap1 activity by heme. Here, to de- cipher the molecular events underlying the actions of Hsp90 and Hsp70 in heme regulation, we purified various multichaperone-Hapl complexes and characterized the complexes linked to Hap1 repression and activation by two.dimensional electrophoresis analysis. Notably, we found that in vitro Hap1 is associated continuously with Ssa and its co-chaperones, and this association is not weakened by heme. Heme enhances the interaction between Hap1 and Hsp90. In vivo, defective Ssa, Ydjl, or Sro9 function causes Hap1 derepression in the absence of heme, whereas defective Hsp90 function causes reduced Hap1 activity at high heme concentrations. These results show that continuous association of Hap1 with Ssa, Ydj1, and Sro9 confers Hap1 repression, whereas enhanced association of Hsp90 with the repressed Hapl-Ssa-Ydj 1-Sro9 complex by heme causes Hap1 activation. This novel mechanism of chaperone action may operate to control the activity of other important signal transducers. [ABSTRACT FROM AUTHOR]

γ-Aminobutyric acid type A (GABAA) receptors are major inhibitory neurotransmitter-gated ion channels in the central nervous system. GABAA receptors consist of multiple subunits and exhibit distinct pharmacologicai and channel properties. Of all GABAA receptor subunits, the β subunit is thought to be a key component for the functionality of the receptors. Certain types of GABAA receptors have been found to be constitutively active. However, the molecular basis for spontaneous opening of channels of these receptors is not totally understood. In this study, we showed that channels that contain the BI but not β3 subunits opened spontaneously when these subunits were expressed homomerically or co-expressed with other types of GABAA receptor subunits in Xenopus oocytes. Using subunit chimeras and site-directed mutagenesis, we localized a key amino acid residue, a serine at position 265, that is critical in conferring an open state of the β1 subunit-containing GABAA receptors in the absence of agonist. Moreover, some point mutations of Ser-265 also produced constitutively active channels. The magnitude of spontaneous activity of these receptors was correlated with the molecular volume of the residue at 265 for both homomeric and heteromeric GABAA receptors, suggesting that the spontaneous activity of the β1 subunit-containing GABAA receptors may be mediated through a similar molecular mechanism that is dependent on the molecular volume of the residue at 265. [ABSTRACT FROM AUTHOR]

Targeted cell killing is required for effective treatment of cancers. We previously described the generation of a chimeric immunocasp-3 protein and its potent selective antitumor activity (Jia, L. T., Zhang, L. H., Yu, C. J., Zhao, J., Xu, Y. M., Gui, J. H., Jin, M., Ji, Z. L., Wen, W. H., Wang, C. J., Chen, S. Y., and Yang, A. G. (2003) Cancer Res. 63, 3257–3262). Here we extend the repertoire of another chimeric pro-apoptotic protein immunoGrB, which comprises an anti-HER2 single-chain antibody, a Pseudomonas exotoxin A translocation domain and active granzyme B. Human lymphoma Jurkat cells transfected with the immunoGrB gene expression vector were able to produce and secrete the chimeric protein. The immunoGrB molecule selectively recognized and destroyed HER2-overexpressing tumor cells both in vitro and in nude mouse after intramuscular injection of the immunoGrB expression plasmid. Further in vivo study showed that intravenous administration of immunoGrB gene-modified lymphocytes led to suppression of HER2-overexpressing tumor growth and prolonged animal survival because of continuous secretion of immunoGrB molecules into blood and lymph fluid. These results demonstrate that the chimeric immunoGrB molecule, which is capable of antibody-directed targeting and granzyme B-mediated killing, has therapeutic potential against HER2 tumors, especially in cases in which caspase-dependent apoptosis is inhibited. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the treatment of heart failure. However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial. Secondary effects of increased serum IGF1 levels on other tissues may explain these unfavorable results. The aim of the current study was to examine the role of IGF1 in cardiac myocytes in the absence of secondary effects, and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic function at 3 months of age, and this was maintained at 12-16 months of age. The phosphoinositide 3-kinase (PI3K)-Aktp70S6K1 pathway was significantly activated in hearts from IGF1R transgenics. Cardiac hypertrophy induced by ovcrexpression of IGF1R was completely blocked by a dominant negative PI3K(p110α) mutant, suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110α)-dependent manner. This study suggests that targeting the cardiac IGF1R-PI3K(p100α) pathway could be a potential therapeutic strategy for the treatment of heart failure. [ABSTRACT FROM AUTHOR]

Postnatal cardiac myocytes respond to stress signals by hypertrophic growth and activation of a fetal gene program. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy, and mice lacking the class II HDAC, HDAC9, are sensitized to hypertrophic signals. To further define the roles of HDACs in cardiac hypertrophy, we analyzed the effects of HDAC inhibitors on the responsiveness of primary cardiomyocytes to hypertrophic agonists. Paradoxically, HDAC inhibitors imposed a dose-dependent blockade to hypertrophy and fetal gene activation. We conclude that distinct HDACs play positive or negative roles in the control of cardiomyocyte hypertrophy. HDAC inhibitors are currently being tested in clinical trials as anti-cancer agents. Our results suggest that these inhibitors may also hold promising clinical value as therapeutics for cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Discusses a mouse model with liver-specific deletion of cytochrome p450 reductase (CPR) gene. Reduction of CPR expression with corresponding decrease in liver microsomal cytochrome p450 (CYP); Increase of liver weight in the homozygotes; Absence of alternative redox partners for liver microsomal CYP.

• Foaming phenomenon in thermal analysis was firstly confirmed by a novel micro-video equipment. • A self-assembly video device was designed with an ultra-rapid cooling system, which can tolerate high temperature and continuous heating. • Explained the reason of violent abnormal fluctuation of mass and energy in thermal analysis. • Secondary reactions of evolving gases were simultaneously recorded by the video instrument. The foaming occurring in thermal analysis often results in mass signal fluctuation or delay and finally leads to misunderstanding of reaction mechanism. However, it is very difficult to predict when and how foaming occurs if there is no video instrument for in-situ observation of thermal reactions. In this study, foaming was confirmed by a novel micro-video equipment of self-assembly with an ultra-rapid cooling system, which can tolerate high temperature and continuous heating. The video of heating tartaric acid continuously recorded a complete process of foaming between 200 and 300 °C and thermal analysis indicated the formation mechanism of foaming. The findings are consistent with the consequence of viscosity testing. The secondary reactions of evolving gases were simultaneously recorded by the video instrument, which revealed that foaming was the cause of mass information fluctuation or lag. [Display omitted] [ABSTRACT FROM AUTHOR]

We investigated ten pale, soft, and exudative (PSE), and ten normal meat samples from pig carcasses. The meat quality at 0, 5, 12, and 24 h post-mortem and the key enzyme activities at 0 and 24 h post-mortem were determined. We selected three PSE and three normal samples for proteomics analysis at 0 h and 24 h post-mortem. No remarkable differences in pyruvate kinase (PK) and lactate dehydrogenase (LDH) activity were observed between samples at 0 h post-mortem; however, creatine kinase (CK) activity was significantly higher in PSE meat. Hexokinase (HK) activity in PSE samples was higher than that in normal samples at 24 h post-mortem. Bioinformatics analysis of the proteome showed that PSE was related to glycolysis, TCA cycle, oxidative phosphorylation, muscle tissue structure, signal transduction, and molecular chaperones. This research found that proteins such as troponin T slow skeletal muscle isoform X, GADPH, L-lactate dehydrogenase A chain, and gamma-enolase isoform X1 might be responsible for PSE. • The activity of enzymes related to energy metabolism was compared between PSE pork and normal meat from 0 to 24 h after slaughter. • No differences were observed in the activity of lactate dehydrogenase and pyruvate kinase between PSE and normal meat 0 h after slaughter. • The upregulated expression of proteins involved in glycolysis and the downregulation of the proteins related to the TCA cycle and oxidative phosphorylation might be the reasons for the formation of PSE pork. • The varying expression of cytoskeleton proteins 24 h post-mortem between PSE and normal pork might result in varying tenderness and WHC. [ABSTRACT FROM AUTHOR]

Rice husk-based SiO 2 /C composite is a promising anode material for lithium ion battery, but it remains necessary to explore simple methods to improve its lithium storage performance. In this research, SiO 2 /C was prepared by adjusting ash content of pyrolyzed rice husk (PRH) using NaOH solution to study the effects of ash content adjustment on lithium storage performance of SiO 2 /C. The adjustment significantly affected the pore structure and lithium storage performance of the SiO 2 /C composite. The SiO 2 /C with ash content of 19.2 wt% ash exhibited a superior reversible capacity of 886 mA h/g at 200 mA/g, which ranked among the highest values ever reported for SiO 2 /C composites; this sample also showed excellent cyclic stability and good rate performance (381 mA h/g at 2000 mA/g). The good electrochemical performance was mainly due to the abundant pores (particularly mesopores) in the composite and to the synergistic effect between carbon and SiO 2. Adjusting ash content of char was an effective method for enhancing lithium storage performance of SiO 2 /C. • An adjusting ash content method was proposed to make rice husk-based anode material. • A simple method for effectively enhancing the lithium storage performance of SiO 2 /C was provided. • SiO 2 /C shows a high capacity of 886 mA h/g at 200 mA/g after 100 cycles. • SiO 2 /C displays excellent cycle stability and good rate performance. [ABSTRACT FROM AUTHOR]

• Degradation rate followed the order: 2,4,6-TBA>2-MCA>2,4-DCA>2,4,6-TCA. • OH and superoxide radical were involved in PAA/UV system. • The primary contribution: TBA (light radiation) and TCA (OH attacking). • The degradation pathway of haloanisoles in PAA/UV process were determined. • PAA/UV could largely reduce olfactory discomfort and health risk of haloanisoles. This study reported the kinetics and mechanism of degradation of odorant haloanisoles by peracetic acid combined with UV irradiation (PAA/UV). The removal efficiency of haloanisoles by PAA/UV was more than 92 % after 1 h reaction at pH 5, 25 °C, [HAs] =50 μg/L and [PAA] = 10 mg/L. The degradation of haloanisoles was fitted by the first-order kinetic model, and the rate constants of various haloanisoles followed the order: 2,4,6-tribromoanisole (2,4,6-TBA, (9.25 ± 0.71)×10−2 s-1) > 2-monochloroanisole (2-MCA, (8.00 ± 0.34)×10−2 s-1) > 2,4-dichloroanisole (2,4-DCA, (6.24 ± 0.55)×10−2 s-1) > 2,4,6-trichloroanisole (2,4,6-TCA, (5.05 ± 0.04)×10−2 s-1). The contribution of PAA (mainly composed of free radicals produced from PAA activation by UV) to the degradation rate of chloroanisoles in PAA/UV process ranged from 24 % to 36 %, while 25 % to the degradation rate of bromoanisole. Direct photolysis contributed much more to the removal of bromoanisole (42 %) than chloroanisoles (9–14 %). The inhibition of tert -butanol on degradation demonstrated the existence of ·OH, and superoxide radical and carbon-centered radicals were also probably existed in PAA/UV process. Combining density functional theory (DFT) calculation and products analysis, the degradation pathway of haloanisoles in PAA/UV process were determined. The odor and toxicity evaluation indicated PAA/UV process could reduce olfactory discomfort and health risk of haloanisoles. [ABSTRACT FROM AUTHOR]

The energy intensive industries of China consumes the highest share of coal that accounts for 93.69% of China's total coal consumption. Hence, these industries are important to achieve the goals to reduce carbon emission and energy conservation. The LMDI decomposition analysis is used to investigate the factors affecting coal consumption in these industries. The empirical findings indices that first, gross industrial output and structural changes had accelerated coal consumption, whereas energy intensity de-accelerated coal consumption. Second, technological improvements boosted industrial growth rate. Finally, results also reveal that there exists a coal rebound effect in energy intensive industries with the maximum at 35.07% in 2016, with an increasing trend during 1990–2016. The present research can help the policymakers to design a pinpointed policy framework to reduce carbon emission and coal conservation. • The coal rebound effect is evaluated by applying a well-designed mechanism. • LMDI model is applied to decompose the total coal consumption. • The technological indicator is estimated by using the resource intensity method. • Coal intensity deaccelerated, while output growth accelerated coal consumption. • Coal rebound effect is estimated as 35.07% in China's energy intensive industries. [ABSTRACT FROM AUTHOR]

This work reported the role of pyrene in formation of naturally occurring silver nanoparticles (AgNPs) via the reduction of silver ions by humic acid under the UV irradiation in the aquatic environment. An increase in temperature (25–90 °C), pH (5–9) or concentration of humic acid (2.5–15 mg/L) led to an enhanced formation of AgNPs. The TEM images indicated the formed AgNPs were spherical with an average particle size of ∼20 nm. Pyrene showed a limited capacity for the photoreduction of silver ions, and when both pyrene and humic acid were present, pyrene would compete with humic acid for the reduction of silver ions. However, the presence of pyrene would enhance the stability and suppress the antibacterial activity of natural AgNPs. The UV–vis spectra of AgNPs suspensions generated with pyrene did not change within 45 days. The inhibition rates against Escherichia coli of AgNPs generated with pyrene were 8–32% lower than those of AgNPs generated without pyrene. This study provides environmental implications on the fate and ecotoxicity of natural AgNPs with interaction of polycyclic aromatic hydrocarbons. Image 1 • Pyrene showed a limited capacity for the photoreduction of silver ions. • Pyrene would compete with humic acid for the reduction of silver ions. • Pyrene would enhance the stability of naturally occurring silver nanoparticles. • Pyrene would suppress the antibacterial activity of silver nanoparticles. [ABSTRACT FROM AUTHOR]

Palladium(II)-directed chiral metal--organic complex multilayers have been prepared on substrate surfaces through a layer-by-layer (LBL) assembly using hydroquinine anthraquinone-1,4-diyl diether bidentate ligands as linkers. The assembling process was monitored by measuring UV--vis absorption and X-ray photoelectron spectra, as well as scanning electron and atomic force microscopy after each layer. It was shown that the molecular chirality of the ligands was retained in the metal--organic complex multilayers. The LBL multilayer fluorescence spectrum showed a broad band at approximately 365 nm corresponding to the emission from the excited hydroquinine substituents. Cyclic voltammograms revealed a quasi-reversible redox wave couple with cathodic and anodic potentials of -0.35 and -0.05 V (vs. Ag/AgCl) at a potential scan rate of 0.05 V/s, which could be assigned to the redox reaction of metal--organic complexes in the multilayers. Further, the redox potential and the potential separation between cathodic and anodic peaks closely depended on the potential scan rate due to the strong film resistance caused by the closely packed arrangement of the metal--organic complexes in the LBL multilayers. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are an important class of water pollutants because of their known ecological and human toxicity. Electrocoagulation (EC) is a promising technology for mitigating industrial wastewater pollution, but the removal and transformation of PAHs during EC treatment has not yet been understood. Therefore, a paper-making wastewater effluent (PMWW) was employed in this study to investigate the relationship between PAHs’ removal and transformation during EC treatment. The results show that 86% of PAHs were effectively removed not only by the electro-oxidation reactions, but also by adsorption onto Fe hydroxide flocs. The removal and transformation of PAHs were related to the number of rings in their structures. Some PAHs composed of two aromatic rings (e.g., naphthaline and dimethylnaphthalene) were produced from humic acid-like and fulvic acid-like organics in PMWW, while PAHs with three to four rings were degraded, thus being removed efficiently. Therefore, PAH transformation during EC treatment exerted double-sided effects on the removal of PAHs; the net effect appeared to be positive. Overall, this study revealed the existence and importance of PAH transformation during EC treatment and provided useful guidance for pulp and paper mills to improve the design and operation of wastewater treatment facilities. [ABSTRACT FROM AUTHOR]

Electrocoagulation (EC) using iron (Fe), zinc (Zn) and aluminum (Al) electrodes was comparatively applied in the treatment of selenium (Se) in flour production (FP) wastewater. It was indicated that EC treatment with Fe anode obtained highest removal efficiency (79.1%) for Se in the 90 min treatment in the comparative study, which could be attributed to the superior adsorption capacity of in-situ generated iron flocs. Removal of Se resulted from electrodeposition and adsorption to in-situ generated flocs in EC treatment, and the operational conditions significantly influenced the Se removal performance in this work. The results showed the acidic condition and higher current density favored EC treatment on Se removal, EC removed up to 97.8% of Se at pH 4 under 15 mA cm−2, whereas it obtained 83.5% and 50.4% of removal efficiency at pH 7 and 10, respectively. There was competitive adsorption in the process of selenium removal, as the in-situ generated flocs effectively removed 35.6% of humic acid-like (HA-like) substance in FP wastewater after 90 min treatment. The FTIR results showed that HA-like substance mainly contained the protein water hydrogen bond, carboxylate COO antisymmetric stretching and other functional groups. Through the analysis of existence of Se in flocs and wastewater, it can be found that approximately 2.8%–3.92% of Se was removed by electrodeposition process. This study illustrated the Se removal mechanism and provided constructive suggestion for food manufacturing to the metal removal and utilization of advanced treatment. [Display omitted] • The acidic condition and higher current density favored EC treatment on Se removal. • EC (Fe) removed up to 79.1% of Se in the wastewater during 90 min treatment. • The generated flocs had superior adsorption capacity on Se removal. • Removal of Se resulted from electrodeposition and adsorption to generated flocs. • Flour production wastewater was mainly composed of humic acid-like substance. [ABSTRACT FROM AUTHOR]

In this work, both Electrocoagulation (EC) and Fered-Fenton (FF) technologies were used to treat reverse osmosis concentrates (ROC) from petrochemical production. The toxicity reduction capacity and mechanism were comparatively assessed during these two treatments. The results showed that FF exhibited higher capacity to reduce toxicity than EC in the 30 min treatment, which could be attributed to the removal of organic pollutants and heavy metals. The results showed that the ROC contained organics with molecular weight of 1200 g mol−1 and 220 g mol−1, which mainly consisted of the soluble microbial by-product-like and humic acid-like substances. The removal of these organics directly led to the noticeable toxicity reduction. Alkanes, haloalkanes, ketones, PAHs, and other four organic pollutants were the dominant species in the ROC, and the removal of small molecular weight organic pollutants played an essential role in reducing toxicity. FF exhibited stronger capacity to remove PAHs, BTEXS and haloalkanes, and the removal efficiencies for the PAHs were in the following order: 5-ring > 4-ring > 3-ring > 2-ring. The promotion of heavy metals removal appeared to be favorable for decreasing toxicity in ROC. This study illustrated the mechanism of the toxicity reduction and the characteristics of pollutants removal during FF and EC treatments, and provided valuable guidance for petrochemical manufacturing to the toxicity reduction and operation of wastewater treatment facilities. [Display omitted] • The removal of organic pollutants and heavy metals caused the toxicity reduction. • FF could obtain 10.3% lower luminescence inhibition than EC. • SMP-like and HA-like substances were observed to be the most refractory organics. • FF had higher removal efficiency of PAHs, BTEXS and haloalkanes than EC treatment. • The removal of As, Cr, Ni and Pb was crucial for the toxicity reduction. [ABSTRACT FROM AUTHOR]