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Aluminum alloy materials have been extensively used in long-span roof structures, especially in coastal and industrial buildings containing corrosive matters. In this study, new-type aluminum alloy...

Dysregulated lipid metabolism plays crucial roles in various diseases, including diabetes mellitus, cancer, and neurodegeneration. Recent studies suggest that alterations in major lipid metabolic pathways contribute to pathogenesis of lung diseases, including chronic obstructive pulmonary disease (COPD). These changes allow lung tissue to meet the energy needs and trigger anabolic pathways that initiate the synthesis of active molecules directly involved in the inflammation. In this review, we summarize the changes of catabolism and anabolism of lipids, lipid molecules including lipid mediators, lipid synthesis transcription factors, cholesterol, and phospholipids, and how those lipid molecules participate in the initiation and resolution of inflammation in COPD.

Polysaccharides are secreted by many marine bacteria as a strategy for growth, binding trace metals, adhering to solid surfaces, and to survive adverse conditions. Therefore, they have attracted extensive research interest due to their biological roles as well as potential industrial application. Many works have been carried out to study the growth dynamics of polysaccharides producing bacteria. Average polysaccharide production per cell during growth were usually studied in the past. However, most previous works were carried out at the population level, and the research at a single cell level was rare. Atomic force microscopy (AFM) is a powerful tool in studying single microorganisms and their extracellular polysaccharides. Here we investigated the growth dynamics and capsular polysaccharide (CPS) production of a CPS producing bacterium Zunongwangia profunda SM-A87 isolated from deep-sea sediments with AFM. Z. profunda SM-A87 exhibited slow growth rates at 10 °C, which was lower than at optimum growth temperature (30 °C). But the CPS production at 10 °C was much higher than that at 30 °C. Single cell imaging with AFM revealed rod like cell morphology at both temperatures, but filamentous bacteria could sometimes be noticed at 10 °C. The CPSs surrounding bacterial cells were observed, and the fibrils of polysaccharides entangled into networks. The diameter of the capsules and the length of the polysaccharides fibrils increased as cultivation time increased. The average volume of the bacterial cells and capsular polysaccharides surrounding each cell at both temperatures were calculated. The average volume of a single bacterial cell was 0.2–0.3 µm 3 , and it increased in exponential phase and slightly decreased in stationary phase, but the average volume of CPS produced by single cells increased during bacterial growth. CPS production increased to 0.097 ± 0.051 µm 3 per cell at 10 °C in stationary phase, which is larger than that produced at 30 °C (0.055 ± 0.013 µm 3 per cell). We report a novel method of estimating the average bacterial polysaccharide production with AFM. Since polysaccharides-producing bacteria are abundant in marine sediments, this method is potentially useful for studying the biological and ecological role of polysaccharides-producing bacteria from the deep sea in the future.

Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow–derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow–derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM-induced necroptosis and activation of subsequent NF κ light-chain–enhancer of activated B cells (NFKB) signaling. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM-induced inflammatory response in MTOR-deficient macrophages. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM-induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders.

1,2-Carbon atom rearrangement has been broadly applied as a guiding strategy in complex molecule assembly. As it entails the carbon-carbon or carbon-heteroatom bond migration between two vicinal atoms, this type of reaction is capable of generating structural complexity through a molecular skeletal reorganization. This review will focus on recent employment of this strategy in the total synthesis of natural products, highlighting the exceptional utility of such synthetic methodologies in the construction of intricate carbocycles, heterocycles or structurally complex motifs from synthetically more accessible precursors.

Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells. In this study, we aimed to investigate the function of autophagy as well as its upstream and downstream signals in cigarette smoke-induced mucus production in human bronchial epithelial (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the classical autophagy inducers starvation or Torin-1, significantly triggered MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced mucus production. The CSE-induced autophagy was mediated by mitochondrial reactive oxygen species (mitoROS), which regulated mucin expression through the JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable effects on the autophagy-JNK signaling cascade. Airways of mice with dysfunctional autophagy-related genes displayed a markedly reduced number of goblet cells and attenuated levels of Muc5ac in response to cigarette smoke exposure. These results altogether suggest that mitoROS-dependent autophagy is essential for cigarette smoke-induced mucus hyperproduction in airway epithelial cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for chronic airway diseases.

Eleven new cassane-type diterpenoids (1–11), along with 12 known compounds were isolated from the seeds of Caesalpinia minax Hance. Their structures were determined by extensive spectroscopic methods in combination with X-ray diffraction analysis. All the compounds were evaluated for COX-2 inhibitory activity, and displayed different levels of inhibition except for 14 whose C and D rings were connected through a spiro-atom. Among them, compound 23, a furanoditerpenoid lactone with a hydroxyl group at C-1 displayed the most potent inhibitory activity with an inhibition ratio of 82.0% at 4.0 μM, which was stronger than its analog 16 with an additional hydroxyl group at C-2. Further detailed testing showed that both compounds 23 and 16 dose-dependently inhibited the COX-2 enzyme with IC50 values of 2.4 ± 0.1 and 3.2 ± 0.2 μM, respectively. Molecular docking analysis showed significant hydrogen bonding and π–π interactions with the enzyme, and revealed the docking scores 36.3108 and 28.6678 for 23 and 16, respectively, which are consistent with their IC50 values. Cytotoxic assay showed that all these diterpenoids only exhibit weak activities with IC50 values over 50 μM on normal cells. Thus, these diterpenoids might be potential anti-inflammatory agents targeting the COX-2 enzyme with low toxicity.

Carpets made with different blending ratio of bamboo and cotton fibers were treated with modified chitosan by padding process. The best performance of the carpets treated was obtained when the carpets were padding with 70 g /L modified chitosan solution under the roller pressure of 0.14 MPa, and cured at 160°C for 90 min. The antibacterial effect of the carpets treated with modified chitosan was characterized by the inhibition ratio to staphylococcus aureus, escherichia coli and Candida albicans and the lustrating ratio of mite. The treated carpets all showed broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and fungi tested and modified chitosan is effective on anti mite.

An asymmetric fluorination/semipinacol rearrangement of 2-oxa allylic alcohols, as catalyzed by cinchona-alkaloid derivatives, gives chiral β-fluoro ketones with moderate to high levels of enantioselectivity (see scheme). Both enantiomers of the product could be obtained by using the appropriate catalyst.

Anodic coatings were prepared by micro-arc oxidation on AZ91 magnesium alloys with the addition of 0-8 g/L tannic acid. The influences of tannic acid concentration on the conductivity and coating properties were studied. The result shows that with the increase of tannic acid concentration, the solution conductivity decreases and the coating color becomes dark. In the solution with 4 g/L tannic acid, the obtained coatings are the most uniform and achieve the best corrosion resistance.

We detected polysaccharide capsules from Zunongwangia profunda SM-A87 with atomic force microscopy (AFM). The molecular organization of the capsules at the single-polysaccharide-chain level was reported. Furthermore, we found that with ScanAsyst mode the polysaccharide capsules could be detected even in the presence of deliquescent water covering the capsule.

OBJECTIVES Human primary microRNA-155/B-cell integration cluster (BIC) transcript is the precursor of microRNA-155. The overexpression of them has been widely observed in the progression of various types of tumors. Our objective was to investigate the effect of anticancer agents on the expression of BIC and possible signal pathways that involved in. METHODS Quantitative real-time reverse transcriptase polymerase chain reaction was used to measure the expression of BIC. Chemical inhibitors against c-Jun N-terminal kinase 1, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2, protein kinase C, checkpoint kinase 1, and phosphatidylinositol 3 kinase (PI3K) were used for the evaluation of involved signal pathways. RNA interference was used to knock down the expression of ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3 related, and suppressor of morphogenesis in genitalia-1 (SMG-1), and Western blot was carried out to evaluate the knockdown effect. RESULTS B-cell integration cluster expression was induced by a representative anti-pancreatic cancer drug, gemcitabine, in human pancreatic cancer PANC-1 cells. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 and c-Jun N-terminal kinase inhibitors, but not the checkpoint kinase 1 and protein kinase C inhibitors, suppressed the up-regulation of BIC. B-cell integration cluster up-regulation was also significantly inhibited by the PI3K inhibitor wortmannin. RNA interference studies showed that wortmannin-sensitive SMG-1 but not ataxia-telangiectasia mutated or ataxia-telangiectasia and Rad3 related was involved in the up-regulation. CONCLUSIONS Our results show that multiple pathways can be involved in the up-regulation of BIC. Furthermore, we demonstrate for the first time that PI3K SMG-1 is required for gemcitabine-induced up-regulation of BIC transcript.

The natural mulberry silk and high-count combed cotton were chosen as raw materials woven into a thin fabric, with classic colour designed as fashion vertical strips. In dying process, high-quality green dye formulations were used to ensure good quality of yarn; in sizing process, the modified starch based, supplemented by a new polypropylene slurry were combined as sizing, which had high concentration and low viscosity, uniform sizing and improved resistance to mill, reduced the regeneration hairiness; in finishing process, the formaldehyde-free anti-crease finishing agent was applied by wet short steaming process, the fabric had anti-crease property, smooth and non-formaldehyde residue. The material after finishing has firmly quality, smooth and fine, slippery and pleasant, safe and practical, has both the texture and luster of silk, also has the comfort of cotton fabric. Through the selection of raw material, production and finishing process, the eco-environmental was stand out, the colour generous and elegant, excellent performance, good market response. The product development process and wear behavior of this high-grade fabric were described in this article. With the textile low-carbon idea through and living standard’s enhancement, the demand of ecotype textile for consumer is getting more and more broad, for this reason, we have developed new product: the ecotype cotton-silk colur woven taffeta. The natural low tex combed cotton was selected as warp yarn and raw silk as weft, and the colour and style formula were careful designed, the high quality environmental protection dye and the formula in dyeing procedure was selected. In the sizing and after-treatment procedure made the key attract, highlight the green environmental protection performance, the fabric has silky quality and gloss, and has cotton comfort, the colour naturally lofty, has good performance, has good market echo. It satisfied the consumer to lining comfortableness, functionality, artistic request[1]. Presently this product’s development and the production process were shown as follow

Cigarette smoke-induced cell death contributes to the pathogenesis of chronic obstructive pulmonary disease, though the relative roles of apoptosis and autophagy remain unclear. The inducible stress protein heme oxygenase-1 (HO-1) confers cytoprotection against oxidative stress. We examined the relationships between these processes in human bronchial epithelial cells (Beas-2b) exposed to cigarette smoke extract (CSE). CSE induced morphological and biochemical markers of autophagy in Beas-2b cells and induced autophagosome formation as evidenced by formation of GFP-LC3 puncta and electron microscopic analysis. Furthermore, CSE increased the processing of microtubule-associated protein-1 light chain-3 (LC3B-I) to LC3B-II, within 1 hr of exposure. Increased LC3B-II was associated with increased autophagy, since inhibitors of lysosomal proteases and of autophagosome-lysosome fusion further increased LC3B-II levels during CSE exposure. CSE concurrently induced extrinsic apoptosis in Beas-2b cells involving early activation of death-inducing-signaling-complex (DISC) formation and downstream activation of caspases (-8,-9,-3). The induction of extrinsic apoptosis by CSE was dependent in part on autophagic proteins. Reduction of Beclin 1 levels with beclin 1 siRNA inhibited DISC formation and caspase-3/8 activation in response to CSE. LC3B siRNA also inhibited caspase-3/8 activation. The stress protein HO-1 protected against CSE-induced cell death by concurrently downregulating apoptosis and autophagy-related signaling. Adenoviral mediated expression of HO-1 inhibited DISC formation and caspase-3/9 activation in CSE-treated epithelial cells, diminished the expression of Beclin 1, and partially inhibited the processing of LC3B-I to LC3B-II. Conversely, transfection of Beas-2b with ho-1 siRNA augmented CSE-induced DISC formation and increased intracellular reactive oxygen species formation. HO-1 expression augmented CSE-induced phosphorylation of NFkappaB p65 in Beas-2b cells. Consistently, expression of IkappaB, the inhibitor of NFkappaB, increased CSE-induced DISC formation. LC3B siRNA also enhanced p65 phosphorylation. In fibroblasts from beclin 1 heterozygous knockout mice, p65 phosphorylation was dramatically upregulated, while CSE-induced DISC formation was inhibited, consistent with an anti-apoptotic role for NFkappaB and a pro-apoptotic role for Beclin 1. These studies demonstrated an interdependence of autophagic and apoptogenic signaling in CSE-induced cell death, and their coordinated downregulation by HO-1. An understanding of the regulation of cell death pathways during smoke exposure may provide therapeutic strategies in smoke-related illness.

Extracellular signal-regulated protein kinase (ERK), one of the mitogen-activated protein kinase, has been known to be involved in diverse cellular functions. In this work, we found that basically inhibition of this kinase in cultured cells markedly increased the gamma-glutamate-cysteine ligase (GCL; EC 6.3.2.2) activity, but without any considerable induction of the GCL genes. The increased GCL activity consequently elevated the cellular GSH level and eventually enhanced the cellular antioxidant capacity. Genetic inhibition of B-Raf, the upstream of ERK, also resulted in increased GCL activity and GSH level. Recent evidence also suggests that chronic pro-oxidant exposure results in the loss of ERK phosphorylation in vivo. Therefore, the findings in the present study suggest that inhibition of B-Raf/MEK/ERK pathway might be a promising physiological approach to up-regulate GCL activity and GSH. This study would also help us to understand the comprehensive role of the Raf/MEK/ERK pathway in overall physio/pathological conditions.

Oxidative stress and the role of antioxidants are currently one of the most important subjects in the field of life science. In the present study, we assessed the oxidation of plasma lipids induced by free radicals and its inhibition by antioxidants with a fluorescence probe BODIPY. Vitamin E and C-depleted plasma was used to evaluate the inherent action of several antioxidants. BODIPY reacted with free radicals in plasma to emit fluorescence (ex. 510 nm, em. 520 nm), which was suppressed by the antioxidants in a concentration-dependent manner. However, the suppression of fluorescence emission by antioxidants did not always correlate quantitatively with the suppression of lipid peroxidation. For example, alpha-tocopherol suppressed BODIPY fluorescence but enhanced the peroxidation of plasma lipids in the absence of ascorbic acid. 2,2,5,7,8-Pentamethyl-6-chromanol, a vitamin E analogue without a phytyl side chain, almost completely suppressed both fluorescence emission and lipid peroxidation in the plasma. These results show that BODIPY can be used as a convenient probe for radical scavenging, but that care should be taken for the evaluation of antioxidant capacity.

Objective The relevance of oxidative stress in mice fed a choline-deficient diet (CDD) was investigated in relation to the oxidative stress marker, hydroxyoctadecadienoic acid (HODE) in comparison with F2-isoprostanes. Further, the protective effects of antioxidants against oxidative damage were assessed by using HODE. Methods We recently proposed total HODE as a biomarker for oxidative stress in vivo. Biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert various oxidation products of linoleates to HODE. In the present study, this method was applied to measure oxidative damage in mice induced by CDD for 1 mo. Results CDD, when compared with choline-controlled diet (CCD), increased liver weight and fatty acid accumulation but the increase in body weight was less significant. Remarkable increases in HODE and 8-iso-prostaglandin F2α in liver and plasma were observed when mice were fed with the CDD for 1 mo compared with the CCD. The HODE level was about two to three orders higher than the F2-isoprostane level. This increase was decreased to the level of the CCD when α-tocopherol or 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, a potent synthetic antioxidant, was mixed with the CDD. The stereoisomer ratio of HODE (9-and-13 (Z,E)-HODE/9-and-13 (E,E)-HODE) was decreased by CDD compared with CCD, which was spared by the addition of α-tocopherol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran. However, the increase in plasma glutamic-pyruvic transaminase and fatty acids in liver induced by the CDD was not recovered by any antioxidant. Conclusions This study clearly demonstrated that oxidative stress was involved in fatty liver formation induced by the CDD and that HODE was a good biomarker for an oxidative stress in vivo.

The adaptive response induced by the lipid peroxidation products, such as phosphatidylcholine hydroperoxide, lysophosphatidylcholine (LysoPC), 15-deoxy-Delta(12,14)-prostaglandin J(2), 4-hydroxynonenal (4-HNE), hydroxyoctadecadienoic acid, 7-hydroxycholesterol, and cholesterol 5beta,6beta-epoxide, was investigated in this study. Although these products have been implicated in oxidative stress-related diseases, pretreatment with such compounds at sublethal concentrations significantly protected PC12 cells against subsequent oxidative stress induced by 6-hydroxydopamine. Moreover, 4-HNE and LysoPC also exhibited adaptive protection in human arterial endothelial cells. These findings suggest a general hormetic effect of such compounds in cell cultures and may lead to a reappraisal of the eventual role of reactive oxygen species and lipid peroxidation in organisms.

4-Hydroxynonenal (4-HNE) is one of the major end products of lipid peroxidation. It has been widely accepted that 4-HNE can induce oxidative stress, implicating into extensive stress-related diseases. In the present study, however, 4-HNE was found to exert adaptive cytoprotective effect at low concentrations, which was primarily through induction of thioredoxin reductase 1 (TR1) via transcriptional activation of NF-E2-related factor 2 (Nrf2). Pretreatment with 4-HNE at sublethal concentrations significantly protected PC12 cells against the subsequent oxidative cell death induced by H2O2 and 6-hydroxydopamine. The cellular antioxidative glutathione system did not show any considerable changes, whereas the TR1 activity as well as the mRNA level was significantly elevated by the 4-HNE treatment. Cells treated with TR1 small interfering RNA exhibited less resistance to oxidative stress, and the adaptive response was completely abolished. The Nrf2 was transcriptionally activated by 4-HNE. Cells treated with Nrf2-small interfering RNA exerted lower constitutive levels of TR1 and exhibited less resistance to oxidative stress, and the 4-HNE-induced TR1 expression and subsequent adaptive response were again abolished in such cells. Treatment with 4-HNE at the adaptive concentration induced transient activation of extracellular signal-regulated protein kinase 1/2 and Akt/protein kinase B. Pharmacological inhibition of both these kinase pathways effectively attenuated 4-HNE-induced TR1 expression and subsequent adaptive protection. The above findings, taken together, suggest that stimulation with 4-HNE at sublethal concentrations induces adaptive response and enhances cell tolerance, primarily through induction of TR1 via transcriptional activation of Nrf2 signaling pathway, thereby protecting cells against the forthcoming oxidative stress.

The adaptive responses to H2O2 and the resulting protective effect against oxidative stress have been investigated using PC12 cells. Pretreatment of sublethal doses of H2O2 significantly protected PC12 cells against the cytotoxicity induced by lethal H2O2. The endogenous antioxidant defense systems, catalase and glutathione peroxidase, were enhanced quickly by the pretreatment of low doses of H2O2. This pretreatment also exerted protective effect against the oxidative insults induced by 6-hydroxydopamine and paraquat, but not against alkyl peroxyl radicals. Our results, taken together, suggest that the stimulation by low dose of H2O2 enriches the cellular antioxidant defense systems, thereby enhancing cell tolerance against the forthcoming oxidative insults induced by H2O2 and related hydroxyl radicals.

Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring phytoalexin present in grapes and other foods, has been reported to possess chemopreventive effects as revealed by its striking inhibition of diverse cellular events associated with tumor initiation, promotion and progression. In our present study, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), when treated with the cultured human mammary epithelial (MCF-10A) cells, induced the expression of cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) that are responsible for the oxidation of 17beta-estradiol to produce catechol estrogens. Resveratrol strongly inhibited the TCDD-induced aryl hydrocarbon receptor (AhR) DNA binding activity, the expression of CYP1A1 and CYP1B1 and their catalytic activities in MCF-10A cells. It also reduced the formation of 2-hydroxyestradiol and 4-hydroxyestradiol from 17beta-estradiol by recombinant human CYP1A1 and CYP1B1, respectively. Furthermore, resveratrol significantly attenuated the intracellular reactive oxygen species (ROS) formation and oxidative DNA damage as well as the cytotoxicity induced by the catechol estrogens. Our data suggest that CYP1A1- and CYP1B1-catalyzed catechol estrogen formation might play a key role in TCDD-induced oxidative damage, and resveratrol can act as a potential chemopreventive against dioxin-induced human mammary carcinogenesis by blocking the metabolic formation of the catechol estrogens and scavenging the ROS generated during their redox cycling.

The adsorption and reactivity of acrylic acid on clean and preoxidized Ni(111) have been examined under ultrahigh vacuum (UHV) conditions using reflection absorption infrared spectroscopy (RAIRS). On clean Ni(111), acrylic acid molecules that adsorb as dimers at 140 K subsequently decompose between 240 and 310 K into surface-bound acrylate species and η1(O)-acrylic acid monomers attached to the surface through the lone pair electrons of the carbonyl O atom. On Ni(111)-p(2 × 2)-O, facile deprotonation of acrylic acid occurs at 240 K to yield upright symmetrically bound acrylate species. Increasing the coverage results in tilting of the acrylate species as a consequence of steric hindrance and repulsive dipolar interactions. An alternative synthetic route to stable surface-bound acrylate monolayers has also been achieved through O-induced nucleophilic substitution of acryloyl chloride on Ni(111)-p(2 × 2)-O.

The antioxidant effect of resveratrol (3,4',5-trihydroxy-trans-stilbene) and its analogues, that is, 4-hydroxy-trans-stilbene (4-HS), 3,5-dihydroxy-trans-stilbene (3,5-DHS), 4,4'-dihydroxy-trans-stilbene (4,4'-DHS), 3,4-dihydroxy-trans-stilbene (3,4-DHS), 3,4,5-trihydroxy-trans-stilbene (3,4,5-THS) and 3,4,4'-trihydroxy-trans-stilbene (3,4,4'-THS), against the peroxidation of linoleic acid has been studied in sodium dodecyl sulfate (SDS) and cetyltrimethyl ammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble azo initiator 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), and the reaction kinetics were studied by monitoring the formation of linoleic acid hydroperoxides. The synergistic antioxidant effect of these compounds with alpha-tocopherol (vitamin E) was also studied by following the decay kinetics of alpha-tocopherol and the reaction intermediate, the alpha-tocopheroxyl radical. Kinetic analysis of the antioxidant process demonstrates that these compounds are effective antioxidants in micelles used either alone or in combination with alpha-tocopherol. The antioxidative action involves trapping the propagating lipid peroxyl radical and reducing the alpha-tocopheroxyl radical to regenerate alpha-tocopherol. It was found that the antioxidant activity of resveratrol analogues depends significantly on the position of the hydroxyl groups, the oxidation potential of the molecule and the reaction medium. Molecules with ortho-dihydroxyl and/or para-hydroxyl functionalities possess high activity.

The first total synthesis of polycyclic Stemona alkaloid maistemonine has been achieved. The efficient approach features a stereoselective intramolecular Schmidt reaction, a ketone-ester condensation, and a Reformatsky reaction. Additionally, another Stemona alkaloid stemonamide was divergently synthesized from a common intermediate.

Efficient intramolecular N/O-nucleophilic cyclization of 2-aryl indoles has been developed to afford the corresponding 2-aza-3-oxaindolines and 3-indolinones in 80–95% yield. The methods provided convenient access to fused imidazo[1,2-c]oxazolidinone, oxazolidine, or tetrahydro-1,3-oxazine cores under mild conditions.

FR901464 (1) and spliceostatin A (2) are potent inhibitors of spliceosomes. These compounds have shown remarkable anticancer activity against multiple human cancer cell lines. Herein, we describe efficient, enantioselective syntheses of FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of their splicing activity. Syntheses of spliceostatin A and FR901464 were carried out in the longest linear sequence of 9 and 10 steps, respectively. To construct the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction, Achmatowicz rearrangement, Michael addition, and reductive amination as key steps. The remarkable diastereoselectivity of the Michael addition was specifically demonstrated with different substrates under various reaction conditions. The side chain B was prepared from an optically active alcohol, followed by acetylation and hydrogenation over Lindlars catalyst. The other densely functionalized tetrahydropyran C-ring was derived from readily available (R)-isopropylidene glyceraldehyde through a route featuring 1,2-addition, cyclic ketalization, and regioselective epoxidation. These fragments were coupled together at a late stage through amidation and cross-metathesis in a convergent manner. Six key diastereomers were then synthesized to probe the importance of specific stereochemical features of FR901464 and spliceostatin A, with respect to their in vitro splicing activity. © 2014 American Chemical Society.

Efficient intramolecular N/O-nucleophilic cyclization of 2-aryl indoles has been developed to afford the corresponding 2-aza-3-oxaindolines and 3-indolinones in 80–95% yield. The methods provided convenient access to fused imidazo[1,2-c]oxazolidinone, oxazolidine, or tetrahydro -1,3-oxazine cores under mild conditions.

A short and improved synthesis of the title compounds is presented in 19 and 20 total steps, respectively.

Antioxidant effects of the principal polyphenolic components extracted from green tea leaves, i.e., (−)-epicatechin (EC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin gallate (EGCG), against peroxidation of linoleic acid have been studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a lipid-soluble azo initiator di-tert-butyl hyponitrite (DBHN) and the reaction kinetics were followed by formation of linoleic acid hydroperoxides and consumption of the antioxidant. Kinetic analysis of the antioxidation process demonstrates that these green tea polyphenols are effective antioxidants in micelles used either alone or in combination with α-tocopherol (vitamin E), but their antioxidative behaviour and relative effectiveness are substantially different from those in the water-soluble initiator AMPAD-initiated peroxidations reported previously. The antioxidative action of the green tea polyphenols (GOHs) in DBHN-initiated peroxidation involves trapping the initiating tert-butoxyl radical and the propagating linoleic acid peroxyl radicals. However, the GOHs could not participate in the α-tocopherol recycling reaction as in the case of AMPAD-initiated reactions due to their very fast reaction with the initiating tert-butoxyl radical.

Construction of the polyaryl quaternary unit through a ZnBr2 catalyzed tandem coupling/semipinacol rearrangement participated by allylic cations was reported for the first time.

The synergistic antioxidant mechanisms of α-tocopherol (vitamin E) with green tea polyphenols and β-carotene are discussed on the basis of kinetic studies on the reactions of α-tocopheroxyl radical with the green tea polyphenols, β-carotene and retinal by stopped-flow electron paramagnetic resonance technique, and on the inhibition of lipid peroxidation by these antioxidants.

The antioxidant effect of the main polyphenolic components extracted from green tea leaves, i.e., (−)-epicatechin (EC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC), (−)-epigallocatechin gallate (EGCG) and gallic acid (GA), against peroxidation of linoleic acid has been studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble azo initiator 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AMPAD) and the reaction kinetics were followed by formation of linoleic acid hydroperoxides and consumption of the antioxidant. Kinetic analysis of the antioxidation process demonstrates that these green tea polyphenols are effective antioxidants in micelles used either alone or in combination with α-tocopherol (vitamin E). The antioxidative action may involve trapping the initiating radicals in the bulk water phase, trapping the propagating lipid peroxyl radicals on the surface of the micelle and regenerating α-tocopherol by reducing α-tocopheroxyl radical. The antioxidant activity of these green tea polyphenols depends significantly on the microenvironment of the reaction medium, the oxidation potential and the size of the molecule.

Roots and rhizomes of the stemonaceous plant have long been used for the treatment of respiratory diseases and as domestic insecticides in traditional folk medicine of East Asia. So far, over 130 structurally diverse Stemona alkaloids have been isolated from the monocotyledonous family Stemonaceae. These Stemona alkaloids have fascinating architectures and potential biological activities, which have provoked broad interests in their total synthesis. Among the Stemona alkaloids, parvineostemonine (1a), isolated from Stemona parviflora by Ye and co-workers in 2003, is a unique molecule which differs from the typical Stemona alkaloids such as 1b–1e (Figure 1). Parvineostemonine fea

Antimicrobial peptides are promising alternative antimicrobial agents compared to conventional antibiotics. Understanding the mode of action is important for their further application. We examined the interaction between trichokonin VI, a peptaibol isolated from Trichoderma pseudokoningii, and Bacillus subtilis, a representative Gram-positive bacterium. Trichokonin VI was effective against B. subtilis with a minimal inhibitory concentration of 25 µM. Trichokonin VI exhibited a concentration- and time-dependent effect against B. subtilis, which was studied using atomic force microscopy. The cell wall of B. subtilis collapsed and the roughness increased upon treatment with trichokonin VI. Nanoindentation experiments revealed a progressive decrease in the stiffness of the cells. Furthermore, the membrane permeabilization effect of trichokonin VI on B. subtilis was monitored, and the results suggest that the leakage of intracellular materials is a possible mechanism of action for trichokonin VI, which led to alterations in the morphological and nanomechanical properties of B. subtilis.

Diaryl allylic tertiary alcohols afford up to 93% enantioselectivity by use of a cinchona-derived catalyst and NBS as brominating reagent.

A full account of the total synthesis of (±)-maistemonine, (±)-stemonamide, and (±)-isomaistemonine is presented. Two approaches have been developed to construct the basic pyrrolo[1,2-a]azepine core of the Stemona alkaloids, featuring a tandem semipinacol/Schmidt rearrangement of a secondary azide and a highly stereoselectively desymmetrizing intramolecular Schmidt reaction, respectively. To build the common spiro-γ-butyrolactone, a new protocol was carried out by utilizing an intramolecular ketone-ester condensation as the key transformation. The vicinal butyrolactone moiety of (±)-maistemonine was stereoselectively introduced via a one-pot procedure involving the epimerization at C-3 and carbonyl allylation/lactonization. Moreover, (±)-stemonamide was divergently synthesized from a common intermediate, and (±)-isomaistemonine was obtained via the epimerization of (±)-maistemonine at C-12.

The reaction allows the construction of two adjacent stereocenters: a chiral oxo-quaternary carbon, and a functionalizable halogen.

A novel asymmetric halogenation/semipinacol rearrangement reaction catalyzed by cinchona alkaloid derivatives was developed. Two types of β-haloketones (X = Br, Cl) were obtained with up to 95% yield and 99% enantiomeric excess. The desired (+) and (−) enantiomers of the β-haloketones were readily obtained.

Treatment of the azide (I) with TiCl4 results in a new and efficient formation of the spiro compound (II).

A TiCl(4)-promoted tandem intramolecular Prins cyclization/Schmidt reaction has been designed and developed to be an efficient method for the construction of the azaspiro[4,4]nonane. The present tandem protocol has been employed to construct the tricyclic azaquaternary skeleton (ring A, B, and C) of stemonamine.

Intermolecular condensation reaction of 1,3,5-triarylenynols catalyzed by gold as Lewis acid was reported for the first time; the products with unique structures have potential applications in materials chemistry, and tandem reaction product 3n has been used to detect mercury ions as an organic molecular probe.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. Methodology and Principal Findings: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSEinduced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1 2/2 mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. Conclusions: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

Free radicals induce oxidative stress in vivo, leading to various disorders and diseases. In the present study, the effect of oxygen pressure on the cytotoxicity induced by free radicals was studied. It was found that alkyl radicals markedly aggravated Jurkat cell apoptosis under low oxygen pressure and this was ascribed to a hypoxic condition caused by the consumption of oxygen by alkyl radicals giving peroxyl radicals and subsequent lipid peroxidation by a chain mechanism. The intracellular lipid hydroperoxides significantly increased at an early time point even under hypoxia. Cytochrome c was released from the mitochondria, and caspase-9 as well as caspase-3 was activated during apoptosis, indicating that cell death followed by the intrinsic, mitochondrial apoptosis pathway. Pretreatment with VAD-FMK, a caspase inhibitor, attenuated the apoptosis induced by alkyl radicals under hypoxia. Moreover, pretreatment with various antioxidants also significantly rescued the cells from apoptosis. Taken together, the results indicate that free radicals induced hypoxic conditions, which accelerated mitochondria-dependent cell apoptosis.

It has been hypothesized that oxidative modification of low density lipoprotein plays a key role in the pathogenesis of atherosclerosis. In order to elucidate the role of lipid oxidation and its inhibition in vivo, apolipoprotein E and alpha-tocopherol (alphaT) transfer protein double knockout (ApoE(-/-)alpha-TTP(-/-)) and apolipoprotein E knockout (ApoE(-/-)) mice fed with a vitamin E-depleted diet and a diet containing 0.002 wt.% alphaT, respectively, were used with or without the treatment of a synthetic antioxidant 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653, 0.2 wt.%). The lipid oxidation markers of total hydroxylinoleic acid (tHODE), 8-iso-prostaglandin F(2alpha), and 7-hydroxycholesterol (t7-OHCh) in the blood, liver, and brain were inclusively measured with or without an excessive cholesterol-feeding (Ch-diet). The tHODE levels were elevated by Ch-diet in the plasma and brain of ApoE(-/-)alpha-TTP(-/-) mice and in the liver of ApoE(-/-) mice without BO-653. The levels of t7-OHCh in the liver were also increased due to the Ch-diet, and the ratio of t7-OHCh to the parent compound cholesterol was reduced to the control levels by BO-653. In summary, it was demonstrated by biomarkers, tHODE and t7-OHCh, that the added BO-653 in their diets exerted antioxidative effects in vivo under the condition of reduced vitamin E.