Acyl-coenzyme A:cholesterol acyltransferases Chang, Ta-Yuan; Li, Bo-Liang; Chang, Catherine C. Y ...
American journal of physiology: endocrinology and metabolism,
07/2009, Volume:
297, Issue:
1
Journal Article
Peer reviewed
Open access
1 Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire; 2 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for ...Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Submitted 12 November 2008
; accepted in final form 12 January 2009
ABSTRACT
The enzymes acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs) are membrane-bound proteins that utilize long-chain fatty acyl-CoA and cholesterol as substrates to form cholesteryl esters. In mammals, two isoenzymes, ACAT1 and ACAT2, encoded by two different genes, exist. ACATs play important roles in cellular cholesterol homeostasis in various tissues. This chapter summarizes the current knowledge on ACAT-related research in two areas: 1 ) ACAT genes and proteins and 2 ) ACAT enzymes as drug targets for atherosclerosis and for Alzheimer's disease.
acyl-coenzyme A:cholesterol acyltransferase inhibitors; atherosclerosis; Alzheimer's disease
Address for reprint requests and other correspondence: T. Y. Chang, Dept. of Biochemistry, Dartmouth Medical School, 1 Rope Ferry Rd., Hanover, NH 03755-1404 (e-mail: Ta.Yuan.Chang{at}Dartmouth.edu )
Chinese herb Radix sophorae tonkinensis extract oxymatrine shows anticancer effects. This study evaluated the role of oxymatrine in colorectal cancer (CRC) and the underlying molecular events in ...vitro and in vivo. CRC cells were treated with different doses of oxymatrine to assess cell viability, reactive oxygen species production, gene expression, and gene alterations. Meanwhile, mouse xenograft and liver metastasis models were used to assess the effects of oxymatrine using histology examination, transmission electron microscopy, and Western blot, respectively. Our results showed that oxymatrine treatment triggered CRC cell mitophagy to inhibit CRC cell growth, migration, invasion, and metastasis in vitro and in vivo. At the gene level, oxymatrine inhibited LRPPRC to promote Parkin translocation into the mitochondria and reduce the mitophagy‐activated NLRP3 inflammasome. Thus, oxymatrine had an anticancer activity through LRPPRC inhibition, mitophagy induction, and NLRP3 inflammasome suppression in the CRC cell xenograft and liver metastasis models. In conclusion, the study demonstrates the oxymatrine anti‐ CRC activity through its unique role in regulating CRC cell mitophagy and NLRP3 inflammasome levels in vitro and in vivo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Transition‐metal catalyzed enantioconvergent cross‐coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α‐disubstituted amino acids. However, the construction ...of chiral C−N bonds between tertiary‐carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper‐catalyzed enantioconvergent radical C−N cross‐coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N‐ligand with a long spreading side arm. An array of α,α‐disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α‐fully substituted amine building blocks.
A copper‐catalyzed enantioconvergent radical C−N cross‐coupling of tertiary alkyl halides with sulfoximines (as ammonia surrogates) was realized by employing a chiral anionic N,N,N‐ligand with a long spreading side arm under mild conditions. An array of valuable α,α‐disubstituted amino acids could be furnished with good efficiency (up to 95 % yield) and enantioselectivity (up to >99 % ee).
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Reducing hot-carrier relaxation rates is of great significance in overcoming energy loss that fundamentally limits the efficiency of solar energy utilization. Semiconductor quantum dots are expected ...to have much slower carrier cooling because the spacing between their discrete electronic levels is much larger than phonon energy. However, the slower carrier cooling is difficult to observe due to the existence of many competing relaxation pathways. Here we show that carrier cooling in colloidal graphene quantum dots can be 2 orders of magnitude slower than in bulk materials, which could enable harvesting of hot charge carriers to improve the efficiency of solar energy conversion.
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Warm-mix asphalt technology has been applied to recycled rubber asphalt binder (RAB), which forms warm-mixed crumb rubber-modified asphalt binder (W-RAB) as a “green” material for environmental ...conservation and to enhance road performance. Furthermore, low-temperature cracking is one of the major distresses for asphalt pavement, which drastically restricts ride quality and service level. Therefore, the main objective of this study is to comparatively analyze the low-temperature properties of W-RABs based on thermal stress and the simple fractional model. W-RABs were obtained by mixing 60 mesh recycled rubber (CR) and two different types of warm-mix additives, namely viscosity reducer (1, 2, and 3%) and surfactant (0.4, 0.6, and 0.8%). First, Hopkins and Hamming’s numerical algorithm and the Boltzmann superposition principle were used for obtaining thermal stress σT. Subsequently, critical cracking temperature Tcr was derived using the single asymptote procedure (SAP) theory. Second, the simple fractional viscoelasticity model was used to calculate the creep compliance, damping ratio, and dissipation energy ratio, and the results were compared with the Superpave protocol results obtained with bending beam rheometer (BBR) tests. The results showed that a combination of CR and warm-mix additives could slightly improve the thermal crack resistance of the asphalt binder. The addition of 0.6% surfactant yielded the optimum performance, while only a high dosage (3%) of viscosity reducer provided a marked improvement in efficiency, which decreased with a decrease in temperature. This study recommends the use of RAB composited with 0.6% surfactant for areas with extremely low temperature.
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Accurate estimation of land surface temperature (LST) is crucial for ecological environment monitoring and climate change studies in mountainous areas. The current LST retrieval algorithms were ...developed without accounting for the topographic effect, which can only be used to retrieve LST over relatively flat surfaces. Due to the impact of 3-D structure of mountainous surfaces, rugged terrain makes the processes of thermal radiation more complex. In this study, a radiative transfer equation (RTE)-based single-channel algorithm was proposed to retrieve LST with topographic effect correction from the Landsat 8 thermal infrared (TIR) data in mountainous areas. This algorithm accounts for the changes in the thermal radiation components in the TIR RTE caused by the topographic effect. According to the analysis of simulation data, sky-view factor (SVF), atmospheric water vapor content, surface emissivity of target pixel, and average LST of the surrounding terrain have significant influence on the magnitude of the topographic effect. The differences between the LST retrieved without/with topographic effect correction from the Landsat 8 TIR data are related to SVF. The topographic effect should be taken into account in the LST retrieval algorithm when SVF is smaller than 0.7. The largest LST difference of approximately 1 K occurs in the deep valley. The results indicate that LST without topographic effect correction could be overestimated to be as high as 1 K. Due to a lack of in situ LST measurements, the performance of the LST retrieval algorithm in mountainous areas was only evaluated by comparing the brightness temperature (BT) at the top of the atmosphere (TOA) simulated by the DART+MODTRAN model and the TIR RTE over mountainous surfaces at three subregions. There is a good consistency between BT at the TOA simulated by the DART+MODTRAN model and the TIR RTE over mountainous surfaces at the three subregions, with a root-mean-squared error (RMSE) of less than 0.23 K.
A general synthesis of inorganic single-crystalline hollow spheres has been achieved through a mechanism analogous to the Kirkendall effect, based on a simple one-step laser process performed at room ...temperature. Taking TiO2 as an example, we describe the laser process by investigating the influence of experimental parameters, for example, laser wavelength, laser fluence/irradiation time, liquid medium, and concentration of starting materials, on the formation of hollow spheres. It was found that the size-tailored TiO2 hollow spheres demonstrate tunable light scattering over a wide visible-light range. Inspired by the effect of light scattering, we introduced the TiO2 hollow sphere’s scattering layer in quantum dot-sensitized solar cells and achieved a current notable 10% improvement of solar-to-electric conversion efficiency, indicating that TiO2 hollow spheres are potential candidates in optical and optoelectronic devices.
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The adsorption and separation abilities of gases (including CO2, CH4, N2, and H2) in a series of chiral COFs (CCOFs) were studied using the Grand canonical Monte Carlo (GCMC) method, periodic density ...functional theory (DFT) (PBE functional) calculations and accurate dispersion corrected double-hybrid DHDF-D3 to explore the potential application of recently synthesized chiral COFs (Han et al., J. Am. Chem. Soc., 2018, 140, 892–895 and Han et al., J. Am. Chem. Soc., 2017, 139, 8693–8697). In contrast to four classical structures (including IRMOF-1, UMCM-1, COF-5, and ZIF-8), CCOF6 shows a better CO2 adsorption capacity at 298 K in a wide range of pressure from 0 to 100 kPa. More importantly, the selectivity of CO2 over N2, CH4 and H2 in CCOF6 is obviously greater than that of other classic porous materials. GCMC simulation demonstrates that the CO2 molecules prefer the smaller B1 channel in CCOF6 at pressure lower than 10 kPa; however, there is no obvious preferential adsorption site in CCOF5. To better understand the mechanism of CO2 adsorption in CCOFs, the interaction energy between CO2 and CCOFs was calculated by the double-hybrid DFT-D3, confirming the preferred adsorption sites in CCOF6 due to the proper narrow channel and the charge transfer from CO2 to CCOF6. Our well established theoretical calculation reveals that CCOF6, with promising CO2 adsorption and selectivity properties, has the potential to be an excellent material for CO2 adsorption and separation.
The use of antagonistic microorganisms and their volatile organic compounds (VOCs) to control plant fungal pathogens is an eco-friendly and promising substitute for chemical fungicides. In this work, ...endophytic bacterium ETR-B22, isolated from the root of
Gagnep., was found to exhibit strong antagonistic activity against 12 fungal pathogens found in agriculture. Strain ETR-B22 was identified as
based on 16S rRNA and
sequences. We evaluated the antifungal activity of VOCs emitted by ETR-B22. The VOCs from strain ETR-B22 also showed broad-spectrum antifungal activity against 12 fungal pathogens. The composition of the volatile profiles was analyzed based on headspace solid phase microextraction (HS-SPME) gas chromatography coupled to mass spectrometry (GC-MS). Different extraction strategies for the SPME process significantly affected the extraction efficiency of the VOCs. Thirty-two different VOCs were identified. Among the VOC of ETR-B22, dimethyl trisulfide, indole, methyl anthranilate, methyl salicylate, methyl benzoate, benzyl propionate, benzyl acetate, 3,5-di-tert-butylphenol, allyl benzyl ether and nonanoic acid showed broad-spectrum antifungal activity, and are key inhibitory compounds produced by strain ETR-B22 against various fungal pathogens. Our results suggest that the endophytic strain ETR-B22 and its VOCs have high potential for use as biological controls of plant fungal pathogens.
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Tectonically active high relief areas are proposed to have a substantial impact on climate regulation throughout the Cenozoic. Here, we present lithium (Li) isotope data of the dissolved load and ...suspended particulate material from the basins of the Yalong River and the Jinsha River, which drain the high-relief borders of the eastern Tibetan Plateau and constitute the headwaters of the Yangtze River. Dissolved δ7Li values are relatively low and constant in the Jinsha River mainstream (+6.8‰ to +9.7‰) compared to the higher and downstream increasing values in the Yalong River mainstream (+10.8‰ to +17.5‰). Furthermore, dissolved δ7Li values in the major tributaries of the Jinsha and Yalong River are highly variable and increase downstream from +11.4‰ to +29.4‰ and from +9.0‰ to +23.6‰, respectively. Robust correlations between Li, Na, and Cl concentrations identify that evaporite dissolution in the uppermost headwaters of the Jinsha River basin controls the Li budget and riverine δ7Li values of the mainstream and has a significant impact on dissolved Li in the Yangtze River. In contrast to the Jinsha River mainstream, dissolved Li in the Yalong River mainstream and the Jinsha and Yalong River tributaries are dominantly derived from the dissolution of silicates. δ7Li variations in the Yalong River basin and the Jinsha tributaries reflect little Li uptake by clays in the upper reaches and more Li uptake by clays in the lower reaches of the river basins. SWR/D ratios (where SWR is the chemical silicate weathering rate, and D is the total denudation rate) highlight an intermediate silicate weathering intensity under a kinetically limited weathering regime for the study area. However, positive correlations between dissolved δ7Li value and silicate weathering intensity proxies (such as Si/(Nasil + K) and K/(Nasil + K)) indicate an increasing weathering intensity downstream. A positive correlation between dissolved δ7Li values and the annual precipitation and a negative one between δ7Li values and elevation indicates that larger annual precipitation under a flattening relief results in a stronger silicate weathering intensity, thus, more Li uptake in clays and higher riverine δ7Li values in the lower reaches. Compared to the lower reaches of Yangtze River basin (∼+20‰), lower dissolved δ7Li values in its headwater of this study suggest that the increase in δ7Li of seawater over the Cenozoic is influenced by weathering in floodplains that developed due to erosion of high mountains, rather than weathering of mountain belts itself. Combined with silicate weathering rates of the eastern border of the Tibetan Plateau, the highest riverine δ7Li values in its catchments come along with the highest silicate weathering rates and high CO2 consumption, suggesting that a more elevated topography may have an important role in the drawdown of CO2 during the Cenozoic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP