The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers. Arachidonic acid (AA) and its metabolites play critical role in the development of ...breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood. We found that the levels of AA and cytosolic phospholipase A2 (cPLA2) strongly correlated with the signaling activity of mTORC1 and mTORC2 as well as the expression levels of vascular epithelial growth factor (VEGF) in human breast tumor tissues. In cultured breast cancer cells, AA effectively activated both mTOR complex 1 (mTORC1) and mTORC2. Interestingly, AA-stimulated mTORC1 activation was independent of amino acids, phosphatidylinositol 3-kinase (PI3-K) and tuberous sclerosis complex 2 (TSC2), which suggests a novel mechanism for mTORC1 activation. Further studies revealed that AA stimulated mTORC1 activity through destabilization of mTOR-raptor association in ras homolog enriched in brain (Rheb)-dependent mechanism. Moreover, we showed that AA-stimulated cell proliferation and angiogenesis required mTOR activity and that the effect of AA was mediated by lipoxygenase (LOX) but not cyclooxygenase-2 (COX-2). In animal models, AA-enhanced incidences of rat mammary tumorigenesis, tumor weights and angiogenesis were inhibited by rapamycin. Our findings suggest that AA is an effective intracellular stimulus of mTOR and that AA-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer.
Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in ...animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear β-catenin, leading to c-Cbl mediated degradation of β-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses β-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.
Heterogeneous oxidation of liquid cyclohexane by molecular oxygen was carried out over metal-containing ZSM-5 catalysts in a solvent-free system. Among those M-ZSM-5 and M/ZSM-5 catalysts tested, ...Co-containing ZSM-5 catalysts including Co/ZSM-5 (prepared by ion-exchange and calcination) and Co-ZSM-5 (prepared by ion-exchange and drying) showed the best activity for the oxidation of cyclohexane to cyclohexanone and cyclohexanol. Co/ZSM-5 had almost the same activity as Co-ZSM-5 for the cyclohexane oxidation; however, the leaching of cobalt from Co-ZSM-5 readily occurred. Co/ZSM-5 (calcined) catalyst could achieve about 10
mol% conversion of cyclohexane and 97% selectivity of KA-oil (the mixture of cyclohexanone and cyclohexanol) at 393
K under the pressure of 1.0
MPa O
2. In addition, other factors like the temperature, the pressure, the time, various metals, the
tert-butylhydroperoxide (TBHP) addition, and the catalyst reuse were investigated carefully. For the titled oxidation, Co/ZSM-5 was recyclable, and could behave as a truly heterogeneous catalyst.
ABSTRACT
This experiment was conducted to evaluate the effects of bile acids (BAs) on the growth performance and lipid metabolism of broilers fed with different energy level diets. 480 one-day-old ...Arbor Acres broilers (45.01 ± 0.26 g) were allotted to a 2 × 2 factorial design with 2 levels of energy (basal or high-energy level) and 2 levels of BAs (with or without BAs supplementation), resulting in 4 groups of 8 replicates; the experiment lasted 42 d. High-energy diets decreased the feed/gain ratio (F/G) from 1 to 21 d (P < 0.05), and increased the liver index and abdominal fat percentage at 42 d (P < 0.05). The serum total triglyceride (TG) and high-density lipoprotein cholesterol at 42 d were increased by high-energy diets (P < 0.05), while the hepatic lipoprotein lipase (LPL) activity at 21 and 42 d was decreased (P < 0.05). BAs supplementation increased the body weight at 21 d and decreased the F/G during entire period (P < 0.05), as well as improved the carcass quality reflected by decreased abdominal fat percentage at 42 d and increased breast muscle percentage at 21 and 42 d (P < 0.05). The serum TG at 21 and 42 d were decreased by BAs (P < 0.05), and the hepatic LPL activity at 42 d was increased (P < 0.05). In addition, high-energy diets increased the expression of sterol regulatory element binding transcription factor 1, acetyl-CoA carboxylase, and fatty acid synthase (P < 0.05), while BAs diets decreased these genes expression (P < 0.05). Moreover, BAs supplementation also increased the expression of carnitine palmitoyltransferase 1 (P < 0.05), which was increased in high-energy groups (P < 0.05). In conclusion, BAs supplementation could increase growth performance, elevate carcass quality, and improve lipid metabolism in broilers.
It is normally expected that an excellent optical material should have p arrow right s-like transitions at the absorption edge. This is because the strength of p arrow right s-like transitions ...usually is much stronger than those of p arrow right p transitions, especially in those ionic semiconductors where the electronic states are more localized and behave as atomic characters. Here, we demonstrate an exception that the luminescence intensity of hexagonal boron nitride (h-BN) could be at least two orders of magnitude greater than that of AIN, despite the dominated atomic p arrow right p transitions at the absorption edge of h-BN. Using group theory analysis and first-principles calculations, we show that the strong optical transitions in h-BN originate from the unusually strong p arrow right p-like transitions and its "two-dimensional" nature. As learned from h-BN, we demonstrate that one can dramatically increase the absorption or luminescence intensity at the fundamental absorption edge of an optical material by confining its thickness into a few layers, which is much more effective than the commonly used superlattice technology.
A series of Schiff-base complexes has been synthesized by the condensation of 1,2-diaminocyclohexane with salicylaldehyde, 2-pyridinecarboxaldehyde, and 2-hydroxy-1-naphthaldehyde, followed by the ...metallation with manganese (
1,
2,
3a), cobalt (
3b), copper (
3c) and iron (
3d) salts. These Schiff-base ligands
L
1
–
L
3
and complexes
1,
2,
3a–
d were then characterized by IR,
1H NMR,
13C NMR, UV–vis spectra, and DSC measurement. Schiff-base Mn complex (
3a) resulting from
N,
N′-bis(2-hydroxy-1-naphthalidene)cyclohexanediamine (
L
3
) ligand was considerably active for the catalytic epoxidation of styrene under mild conditions, in which the highest yield of styrene oxide reached 91.2
mol%, notably higher than those achieved from simple salt catalysts Mn(Ac)
2·4H
2O and MnSO
4·H
2O. However, another two salen–Mn complexes
1 and
2 derived from ligands
N,
N′-bis(salicylidene)cyclohexanediamine (
L
1
) and
N,
N′-bis(2-pyridine carboxalidene)cyclohexanediamine (
L
2
) exhibited relatively poor activity under identical experimental conditions.
In klystron amplifiers, spurious oscillations caused by the backstreaming electrons from collector may lead to unacceptable instabilities in experiments. To facilitate the fast and accurate analysis ...of such types of self-oscillations, rather than performing time-consuming particle-in-cell (PIC) simulations, the small signal theory to predict threshold conditions of spurious oscillations in klystrons has been further developed and implemented into the klystron computer code KlyC. If spurious oscillation occurs, the frequency and Q of the oscillation mode in a small signal regime can also be predicted. The effectiveness of the proposed threshold prediction method has been demonstrated through benchmarking against PIC codes, showing great agreement with result discrepancies at the several percentage level, while numerical computation time for small signal models is significantly (at least three orders of magnitude) faster than executed in the PIC simulations.
Abstract
The Lobster Eye Imager for Astronomy (LEIA), a pathfinder of the Wide-field X-ray Telescope of the Einstein Probe mission, was successfully launched onboard the SATech-01 satellite of the ...Chinese Academy of Sciences on 2022 July 27. In this paper, we introduce the design and on-ground test results of the LEIA instrument. Using state-of-the-art Micro-Pore Optics (MPO), a wide field of view of 346 square degrees (18.°6 × 18.°6) of the X-ray imager is realized. An optical assembly composed of 36 MPO chips is used to focus incident X-ray photons, and four large-format complementary metal-oxide semiconductor (CMOS) sensors, each of size 6 cm × 6 cm, are used as the focal plane detectors. The instrument has an angular resolution of 4′–8′ (in terms of FWHM) for the central focal spot of the point-spread function, and an effective area of 2–3 cm
2
at 1 keV in essentially all the directions within the field of view. The detection passband is 0.5–4 keV in soft X-rays and the sensitivity is 2–3 × 10
−11
erg s
−1
cm
−2
(about 1 milliCrab) with a 1000 s observation. The total weight of LEIA is 56 kg and the power is 85 W. The satellite, with a design lifetime of 2 yr, operates in a Sun-synchronous orbit of 500 km with an orbital period of 95 minutes. LEIA is paving the way for future missions by verifying in flight the technologies of both novel focusing imaging optics and CMOS sensors for X-ray observation, and by optimizing the working setups of the instrumental parameters. In addition, LEIA is able to carry out scientific observations to find new transients and to monitor known sources in the soft X-ray band, albeit with limited useful observing time available.
Abstract
Distributed photovoltaic is one of the important energy supplies in new-type power system. Notably, when the main transformer is operated in non-directly grounded mode and distributed ...photovoltaic is connected to the low-voltage side, faults such as single-phase grounding short-circuit may cause overvoltage problems at the neutral point of the transformer, thereby posing a threat to the insulation at the neutral point. For the main transformer neutral point voltage offset and gap protection problems, this paper first analyzes the fault characteristics of the network, the operation of the line protection and the neutral point voltage offset after the fault occurs. Furthermore, combined with the distributed photovoltaic output characteristics after the near-system protection action, this paper analyzes that the distributed photovoltaic access after the line protection action may cause the neutral point over-voltage offset to deteriorate further. Moreover, under different matching degrees of distributed capacity and local load, the degree of neutral point voltage deviation when a single-phase fault occurs in a substation with distributed photovoltaic is derived. On this basis, the criterion of gap breakdown of the main transformer and relevant suggestions for installing gap protection are given. Finally, based on the simulation analysis of the single-phase ground fault of the grid-connected line, the boundary of neutral breakdown at different fault moments are obtained, thereby effectively guiding distributed photovoltaic to access new-type power system friendly.
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