Activation of prolyl hydroxylase‐2 for stabilization of mitochondrial stress along with simultaneous downregulation of HIF‐1α/FASN in ER + breast cancer subtype

The present study was undertaken to inquest the chemical activation of prolyl hydroxylase‐2 for the curtailment of hypoxia‐inducible factor‐1α and fatty acid synthase. It was well documented that hypoxia‐inducible factor‐1α and fatty acid synthase were overexpressed in mammary gland carcinomas. After screening a battery of compounds, BBAP‐2 was retrieved as a potential prolyl hydroxylase‐2 activator and validates its activity using ER + MCF‐7 cell line and n‐methyl‐n‐nitrosourea‐induced rat in vivo model, respectively. BBAP‐2 was palpable for the morphological characteristics of apoptosis along with changes in the mitochondrial intergrity as visualized by acridine orange/ethidium bromide and JC‐1 staining against ER + MCF‐7 cells. BBAP‐2 also arrest the cell cycle of ER + MCF‐7 cells at G2/M phase. Afterward, BBAP‐2 has scrutinized against n‐methyl‐n‐nitrosourea‐induced mammary gland carcinoma in albino Wistar rats. BBAP‐2 restored the morphological architecture when screened through carmine staining, haematoxylin and eosin staining, and scanning electron microscopy. BBAP‐2 also delineated the markers of oxidative stress favourably. The immunoblotting and mRNA expression analysis validated that BBAP‐2 has a potentialty activate the prolyl hydroxylase‐2 with sequential downregulating effect on hypoxia‐inducible factor‐1α and its downstream checkpoint. BBAP‐2 also fostered apoptosis through mitochondrial‐mediated death pathway. The present study elaborates the chemical activation of prolyl hydroxylase‐2 by which the increased expression of HIF‐1α and FASN can be reduced in mammary gland carcinoma.     

Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis

Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect.     

Effects of Dietary Fatty Acids and Exercise on Body‐Weight Regulation and Metabolism in Rats

Objective: To assess the interaction of high‐fat diets (HF) made with different dietary fatty acids and exercise on body‐weight regulation, adiposity, and metabolism. Research Methods and Procedures: Male Wistar rats born to dams fed HF diets (40% w/w) made with either fish oil (FO), soybean oil (SO), or palm oil (PO) were fed diets similar to their dams and divided randomly into exercise (EX, swimming) or sedentary control (SD) groups when they were 9 weeks old. EX lasted for 6 weeks. Twenty‐four hours after the last EX bout, fasted rats were killed by decapitation. Chemical analyses and body composition analysis were conducted. Results: The results demonstrated that different fatty acids had different effects on body weight, composition, and metabolism. SO‐fed rats gained the most weight and fat. EX reduced body weight of FO‐ and PO‐fed rats, but SO‐fed rats were still heavier and fatter than other rats. Data from SO‐ and PO‐fed rats suggested that they are insulin resistant and that EX normalized this abnormality. Of the three HF diets used, FO produced the least adverse effects compared with PO and SO. Discussion: Not only the quantity of dietary fat, but also the type of fat used, will produce different effects on body weight and metabolism. EX ameliorates the suggested insulin resistance induced in rats fed either highly saturated or n‐6 polyunsaturated fatty acids. Long‐chain n‐3 polyunsaturated fatty acids, as found in fish oil, are more beneficial than n‐6 polyunsaturated fatty acids when fed in high amounts to rats.     

Wide Potential Window Supercapacitors Using Open‐Shell Donor–Acceptor Conjugated Polymers with Stable N‐Doped States

Supercapacitors have emerged as an important energy storage technology offering rapid power delivery, fast charging, and long cycle lifetimes. While extending the operational voltage is improving the overall energy and power densities, progress remains hindered by a lack of stable n‐type redox‐active materials. Here, a new Faradaic electrode material comprised of a narrow bandgap donor?acceptor conjugated polymer is demonstrated, which exhibits an open‐shell ground state, intrinsic electrical conductivity, and enhanced charge delocalization in the reduced state. These attributes afford very stable anodes with a coulombic efficiency of 99.6% and that retain 90% capacitance after 2000 charge–discharge cycles, exceeding other n‐dopable organic materials. Redox cycling processes are monitored in situ by optoelectronic measurements to separate chemical versus physical degradation mechanisms. Asymmetric supercapacitors fabricated using this polymer with p‐type PEDOT:PSS operate within a 3 V potential window, with a best‐in‐class energy density of 30.4 Wh kg^?1 at a 1 A g^?1 discharge rate, a power density of 14.4 kW kg^?1 at a 10 A g^?1 discharge rate, and a long cycle life critical to energy storage and management. This work demonstrates the application of a new class of stable and tunable redox‐active material for sustainable energy technologies.     

Seasonal changes in European whitefish muscle and invertebrate prey fatty acid composition in a subarctic lake

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Aerobic biodegradation of N-nitrosodimethylamine (NDMA) by axenic bacterial strains

The water contaminant N-nitrosodimethylamine (NDMA) is a probable human carcinogen whose appearance in the environment is related to the release of rocket fuel and to chlorine-based disinfection of water and wastewater. Although this compound has been shown to be biodegradable, there is minimal information about the organisms capable of this degradation, and little is understood of the mechanisms or biochemistry involved. This study shows that bacteria expressing monooxygenase enzymes functionally similar to those demonstrated to degrade NDMA in eukaryotes have the capability to degrade NDMA. Specifically, induction of the soluble methane monooxygenase (sMMO) expressed by Methylosinus trichosporium OB3b, the propane monooxygenase (PMO) enzyme of Mycobacterium vaccae JOB-5, and the toluene 4-monooxygenases found in Ralstonia pickettii PKO1 and Pseudomonas mendocina KR1 resulted in NDMA degradation by these strains. In each of these cases, brief exposure to acetylene gas, a suicide substrate for certain monooxygenases, inhibited the degradation of NDMA. Further, Escherichia coli TG1/pBS(Kan) containing recombinant plasmids derived from the toluene monooxygenases found in strains PKO1 and KR1 mimicked the behavior of the parent strains. In contrast, M. trichosporium OB3b expressing the particulate form of MMO, Burkholderia cepacia G4 expressing the toluene 2-monooxygenase, and Pseudomonas putida mt-2 expressing the toluene sidechain monooxygenase were not capable of NDMA degradation. In addition, bacteria expressing aromatic dioxygenases were not capable of NDMA degradation. Finally, Rhodococcus sp. RR1 exhibited the ability to degrade NDMA by an unidentified, constitutively expressed enzyme that, unlike the confirmed monooxygenases, was not inhibited by acetylene exposure.     

Adiposity in Middle‐aged Women is Associated with Genetic Taste Blindness to 6‐n‐Propylthiouracil

Objective: Taste blindness to the bitterness of 6‐n‐propylthiouracil (PROP) may be a genetic marker for food preferences and dietary choices that ultimately influence body weight. A previous study in middle‐aged women showed that those who were taste blind to PROP (i.e., nontasters) had higher BMIs than those with the greatest sensitivity to PROP (i.e., supertasters). This study tested the hypothesis that the nontaster phenotype was associated with greater adiposity in middle‐aged women. Research Methods and Procedures: Forty women with a mean BMI of 26.6 ± 1.3 kg/m² and a mean age of 41.8 ± 1.8 years were recruited from the local community. They were classified as nontasters (n = 8), medium tasters (n = 18), or supertasters (n = 14) of PROP using a filter paper screening procedure. Anthropometric measures included height, weight, body fatness, triceps skinfold thickness, and waist circumference. Dietary restraint and disinhibition were also measured to assess cognitions associated with body weight. Results: BMI was 6.2 units higher in nontaster women compared with supertaster women (29.7 ± 0.9 vs. 23.5 ± 0.9, respectively; p < 0.05). Body fatness (p < 0.01) and triceps skinfold thickness (p < 0.05) were also higher in these women. Waist circumference showed a trend in the appropriate direction. Although disinhibition was associated with greater adiposity, the relation between PROP status and adiposity was not altered after controlling for disinhibition. Discussion: The PROP nontaster phenotype was strongly associated with several measures of adiposity in middle‐aged women. These data confirm our previous findings and suggest that the PROP polymorphism may be a reliable indicator of weight gain susceptibility.     

Cuticular Hydrocarbon Profiles Differentiate Tropical Fire Ant Populations (Solenopsis geminata,Hymenoptera: Formicidae)

The cuticular hydrocarbons (CHCs) from hexane rinses of workers from two Florida populations (dark and red forms) of the tropical fire ant, Solenopsis geminata, were separated by silica gel chromatography and identified by GC/MS analysis. Both the dark form and the red form produce similar CHCs with carbon chain lengths ranging from 17 to 35. However, the relative percentages of these CHCs were consistently different between the two color forms. The largest CHC component in the dark form is tricosane, and (Z)‐9‐tricosene for the red form. There were several significant differences in percent composition. For example, the dark form was characterized by a low tricosene:tricosane ratio (ca. 0.25), whereas this ratio was > 2.5 for the red form. The ratio of tricosene:tricosane can be used as a diagnostic biomarker to delimit the dark and red forms. Cluster analysis showed that the CHCs patterns of dark form colonies are completely separated from the CHC pattern of red form colonies. Differences in social behaviors like nestmate recognition and polygyny between workers from this dark form and the red form await further investigation.     

Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I' beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide.

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I'beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 --> 1 hydrogen bonds. In addition, a single 4 --> 1 hydrogen bond is also observed at the N-terminus. All five Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C(alpha)-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean tau values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively.     

Interface Engineering for Highly Efficient and Stable Planar p‐i‐n Perovskite Solar Cells

Organic‐inorganic halide perovskite materials have become a shining star in the photovoltaic field due to their unique properties, such as high absorption coefficient, optimal bandgap, and high defect tolerance, which also lead to the breathtaking increase in power conversion efficiency from 3.8% to over 22% in just seven years. Although the highest efficiency was obtained from the TiO₂ mesoporous structure, there are increasing studies focusing on the planar structure device due to its processibility for large‐scale production. In particular, the planar p‐i‐n structure has attracted increasing attention on account of its tremendous advantages in, among other things, eliminating hysteresis alongside a competitive certified efficiency of over 20%. Crucial for the device performance enhancement has been the interface engineering for the past few years, especially for such planar p‐i‐n devices. The interface engineering aims to optimize device properties, such as charge transfer, defect passivation, band alignment, etc. Herein, recent progress on the interface engineering of planar p‐i‐n structure devices is reviewed. This review is mainly focused on the interface design between each layer in p‐i‐n structure devices, as well as grain boundaries, which are the interfaces between polycrystalline perovskite domains. Promising research directions are also suggested for further improvements.     

Dl‐3‐n‐butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF‐κB signalling

In this study, we examined the neuroprotective effects and anti‐inflammatory properties of Dl‐3‐n‐butylphthalide (NBP) in Sprague‐Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL‐positive cells at 7 days post‐injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF‐κB expression at 1 day post‐injury. In a co‐culture system with BV‐2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV‐2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV‐2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF‐κB expression in BV‐2 cells. Our findings demonstrate that NBP may have neuroprotective and anti‐inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF‐κB signalling.     

Differential effect of ascorbic acid and n-acetyl-L-cysteine on arsenic trioxide-mediated oxidative stress in human leukemia (HL-60) cells

Arsenic trioxide (ATO) has been recommended for the treatment of refractory cases of acute promyelocytic leukemia (APL). Recent studies in our laboratory indicated that oxidative stress plays a key role in ATO-induced cytotoxicity in human leukemia (HL-60) cells. In the present investigation, we performed the MTT assay and trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) production in HL-60 cells coexposed to either ascorbic acid (AA) and ATO or to n-acetyl-L-cysteine (NAC) and ATO. The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in MDA levels with increasing doses of AA. In contrary, the addition of NAC to ATO-treated HL-60 cells resulted in a dose-dependent decrease of MDA production. From these results, we conclude that the addition of the AA to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS), whereas the addition of NAC under the same experimental condition significantly (p < .05) decreases the level of ROS formation. On the basis of these direct in vitro findings, our studies provide evidence that AA may extend the therapeutic spectrum of ATO. The coadministration of NAC with ATO shows a potential specificity for tumor cells, indicating that it may not enhance the clinical outcome associated with ATO monotherapy in vivo.     

Solution conformation of a tetradecapeptide stabilized by two di‐n‐propyl glycine residues

The solution conformation of a designed tetradecapeptide Boc‐Val‐Ala‐Leu‐Dpg‐Val‐Ala‐Leu‐Val‐Ala‐Leu‐Dpg‐Val‐Ala‐Leu‐OMe (Dpg‐14) containing two di‐n‐propyl glycine (Dpg) residues has been investigated by ¹H NMR and circular dichroism in organic solvents. The peptide aggregates formed at a concentration of 3 mM in the apolar solvent CDCl₃ were broken by the addition of 12% v/v of the more polar solvent DMSO‐d₆. Successive N_iH N_i+1H NOEs observed over the entire length of the sequence in this solvent mixture together with the observation of several characteristic medium‐range NOEs support a major population of continuous helical conformations for Dpg‐14. Majority of the observed coupling constants ( ) also support ? values in the helical conformation. Circular dichroism spectra recorded in methanol and propan‐2‐ol give further support in favor of helical conformation for Dpg‐14 and the stability of the helix at higher temperature. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN‐induced hepatocellular carcinoma

Cancer metastasis is a complex multi‐step process, responsible for a majority of cancer‐related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi‐factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP‐2 and MMP‐9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti‐oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP‐2 and MMP‐9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co‐treatment significantly decreased the activities of MMP‐2 and MMP‐9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP‐2 and MMP‐9 in rats co‐treated with BA compared to DEN‐induced hepatocellular carcinoma. Our results reveal that BA exerts its anti‐metastatic effect against DEN‐induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP‐2 and MMP‐9. Copyright © 2010 John Wiley & Sons, Ltd.     

Comprehensive Characterisation of n‐Alkylresorcinols and Other Lipid Constituents of Mercurialis tomentosa L. from Alicante,Spain

Mercurialis tomentosa L. has been used in Spanish ethnomedicine. In the present study the first phytochemical characterisation of a lipid fraction from M. tomentosa was performed. The CHCl₃ extraction of aerial parts from M. tomentosa and GC/MS investigations revealed the occurrence of cuticular lipid and wax constituents, like long chain n‐alcohols and n‐aldehydes (C₂₂ – C₃₀), besides several aromatic constituents, i.e., phenylpropanoids and n‐alkylresorcinols. The latter were further purified by CC and analysed by LC/MSⁿ. In contrast to other Mercurialis species, i.e., M. annua, M. perennis, which exclusively contain 5‐n‐alkylresorcinols ( 1a  –  j , C_n), mainly 5‐n‐alkyl‐2‐methylresorcinols ( 2a  –  j , C_n*) with side chain lengths of C₁₅ – C₂₅ were found in M. tomentosa, in addition to 1a  –  j . Thus, the latter compounds may be utilised for analytical characterisation and authentication of M. tomentosa based on fingerprinting methods. For structure elucidation a novel facile total synthesis of one representative 5‐n‐alkyl‐2‐methylresorcinol homologue ( 2d , C₁₉*) was developed, starting with a Grignard reaction from a substituted benzoic acid chloride ( 19 ). The compound obtained by synthesis was identical to the natural product 2d in terms of its chromatographic and spectroscopic features. Futhermore, 2d exhibited satisfactory DPPH free radical scavenging activity (IC₅₀ = 37.8 μm ) when compared to trolox (IC₅₀ = 21.0 μm ), corroborating the antioxidant features of these amphipathic molecules.     

Subtle Roles of Sb and S in Regulating the Thermoelectric Properties of N‐Type PbTe to High Performance

A high ZT (thermoelectric figure of merit) of ≈1.4 at 900 K for n‐type PbTe is reported, through modifying its electrical and thermal properties by incorporating Sb and S, respectively. Sb is confirmed to be an amphoteric dopant in PbTe, filling Te vacancies at low doping levels (<1%), exceeding which it enters into Pb sites. It is found that Sb‐doped PbTe exhibits much higher carrier mobility than similar Bi‐doped materials, and accordingly, delivers higher power factors and superior ZT . The enhanced electronic transport is attributed to the elimination of Te vacancies, which appear to strongly scatter n‐type charge carriers. Building on this result, the ZT of Pb_0.9875Sb_0.0125Te is further enhanced by alloying S into the Te sublattice. The introduction of S opens the bandgap of PbTe, which suppresses bipolar conduction while simultaneously increasing the electron concentration and electrical conductivity. Furthermore, it introduces point defects and induces second phase nanostructuring, which lowers the lattice thermal conductivity to ≈0.5 W m^?1 K^?1 at 900 K, making this material a robust candidate for high‐temperature (500–900 K) thermoelectric applications. It is anticipated that the insights provided here will be an important addition to the growing arsenal of strategies for optimizing the performance of thermoelectric materials.     

Nonfullerene n‐Type Organic Semiconductors for Perovskite Solar Cells

Compared to inorganic semiconductors and/or fullerene derivatives, nonfullerene n‐type organic semiconductors present some advantages, such as low‐temperature processing, flexibility, and molecule structure diversity, and have been widely used in perovskite solar cells (PSCs). In this research news article, the recent advances in nonfullerene n‐type organic semiconductors which function as electron‐transporting, interface‐modifying, additive, and light‐harvesting materials in PSCs are summarized. The remaining challenges and promising future directions of nonfullerene‐based PSCs are also discussed.     

Applied in situ product recovery in ABE fermentation

The production of biobutanol is hindered by the product's toxicity to the bacteria, which limits the productivity of the process. In situ product recovery of butanol can improve the productivity by removing the source of inhibition. This paper reviews in situ product recovery techniques applied to the acetone butanol ethanol fermentation in a stirred tank reactor. Methods of in situ recovery include gas stripping, vacuum fermentation, pervaporation, liquid–liquid extraction, perstraction, and adsorption, all of which have been investigated for the acetone, butanol, and ethanol fermentation. All techniques have shown an improvement in substrate utilization, yield, productivity or both. Different fermentation modes favored different techniques. For batch processing gas stripping and pervaporation were most favorable, but in fed‐batch fermentations gas stripping and adsorption were most promising. During continuous processing perstraction appeared to offer the best improvement. The use of hybrid techniques can increase the final product concentration beyond that of single‐stage techniques. Therefore, the selection of an in situ product recovery technique would require comparable information on the energy demand and economics of the process. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:563–579, 2017