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The Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway controls multiple biological processes, including cell survival, proliferation, and differentiation. Abnormally activated STAT3 signaling promotes tumor cell growth, proliferation, and survival, as well as tumor invasion, angiogenesis, and immunosuppression. Hence, JAK/STAT3 signaling has been considered a promising target for antitumor therapy. In this study, a number of ageladine A derivative compounds were synthesized. The most effective of these was found to be compound 25. Our results indicated that compound 25 had the greatest inhibitory effect on the STAT3 luciferase gene reporter. Molecular docking results showed that compound 25 could dock into the STAT3 SH2 structural domain. Western blot assays demonstrated that compound 25 selectively inhibited the phosphorylation of STAT3 on the Tyr705 residue, thereby reducing STAT3 downstream gene expression without affecting the expression of the upstream proteins, p-STAT1 and p-STAT5. Compound 25 also suppressed the proliferation and migration of A549 and DU145 cells. Finally, in vivo research revealed that 10 mg/kg of compound 25 effectively inhibited the growth of A549 xenograft tumors with persistent STAT3 activation without causing significant weight loss. These results clearly indicate that compound 25 could be a potential antitumor agent by inhibiting STAT3 activation.

To evaluate the month-wise prevalence of subclinical mastitis (SM) and its relations with climatic temperature and humidity, and to provide references for control and prevention of mastitis in dairy cows in Guangdong, China, California mastitis test method was used to determine the monthly prevalence of SM (MPSM, %) of lactating Holstein cows from 11 dairy farms in Guangdong Province, China, including about 516 cows per monthly examination. The average MPSM on a cow and a quarter basis were 30 and 13% respectively, and there was a positive linear correlation between monthly mean air temperature (MT, ?C) and MPSM on a cow basis (r=0.763, P=0.004) or a quarter basis (r=0.577, P=0.049), but there were no correlations between MT and MPSM on a cow or a quarter basis (P>0.05). There was a shift in MPSM trend that the highest MPSM (38.4%) was not for the hottest July with MT at 30.8?C, but for the later September at 27.9?C. The farms need to develop new housing conditions to control cowshed temperatures in the hot season to reduce the mastitis prevalences in the posthot months.

High levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α) are present in atherosclerotic lesions. TNF-α regulates expression of multiple genes involved in various stages of atherosclerosis, and it exhibits proatherosclerotic and antiatherosclerotic properties. ACAT catalyzes the formation of cholesteryl esters (CE) in monocytes/macrophages, and it promotes the foam cell formation at the early stage of atherosclerosis. We hypothesize that TNF-α may be involved in regulating the ACAT gene expression in monocytes/macrophages. In this article, we show that in cultured, differentiating human monocytes, TNF-α enhances the expression of the ACAT1 but not ACAT2 gene, increases the cholesteryl ester accumulation, and promotes the lipid-laden cell formation. Several other proinflammatory cytokines tested do not affect the ACAT1 gene expression. The stimulation effect is consistent with a receptor-dependent process, and is blocked by using nuclear factor-kappa B (NF-kappa B) inhibitors. A functional and unique NF-kappa B element located within the human ACAT1 gene proximal promoter is required to mediate the action of TNF-α. Our data demonstrate that TNF-α, through the NF-kappa B pathway, specifically enhances the expression of human ACAT1 gene to promote the CE-laden cell formation from the differentiating monocytes, and our data support the hypothesis that TNF-α is proatherosclerotic during early phase of lesion development.

DOI：10.3969/j.issn.1672⁃6731.2012.05.023

High-purity ternary Pr13Fe80B7 magnetic powder with high anisotropy is obtained by a modified hydrogenation disproportionation desorption recombination (HDDR) process. It is found that the formation of HDDR Pr13Fe80B7 anisotropy is related to a rodlike disproportionation microstructure.

Microstructural changes of NdFe10.5Mo1.5 and Pr13Fe80B7 compounds during the solid-hydrogenation disproportionation desorption recombination process are investigated in this paper. It is found that the early disproportionated microstructure of NdFe10.5Mo1.5 and Pr13Fe80B7 alloys shows similar rodlike morphology. All the NdH2+X and PrH2+X rods have the same orientation and grow with a definite orientation related to the α-Fe matrix. However, it is different that Mo atoms are found to dissolve in the α-Fe matrix of the NdFe10.5Mo1.5 disproportionated products while the PrH2+X rods are enriched with B in the case of Pr13Fe80B7 alloys. No special crystallographic relationship between the recombined NdFe10.5Mo1.5 or Pr13Fe80B7 and its disproportionated products is observed. A preferred nucleation and growth of recombined Pr2Fe14B grains is found while that of recombined NdFe10.5Mo1.5 grains is not. Thus, the final hydrogenation-disproportionation desorption recombination (HDDR) NdFe10.5Mo1.5NX powder is isotropic while the HDDR Pr13Fe80B7 powder has a strong anisotropy under the same HDDR treatment conditions. In the end, the formation of anisotropy in the HDDR Pr13Fe80B7 and NdFe10.5Mo1.5NX powders is discussed. [ABSTRACT FROM AUTHOR]

Strip-casting technique is used to prepare anisotropic Nd(Fe,Mo)12Nx compounds. It is found that, by this technique, the single-phase Nd(Fe,Mo)12 compounds can be directly obtained without postannealing at a rolling velocity of 3 m/s and with an Fe-to-Mo ratio of 7. Under the same nitrogenation conditions, it is easier to introduce the nitrogen atoms into the strip-cast Nd(Fe,Mo)12 powders than into the conventionally cast powders. The microstructure studies of the ingots show that not only the size of strip cast Nd(Fe,Mo)12 grains is small, but also the size distribution of the grains is narrow as compared with those of conventionally cast ingots. Thus, the strip-casting technique is used to synthesize the anisotropic powders of Nd(Fe,Mo)12Nx with a Br of 1.10 T, an iHc of 448 kA/m, and a (BH)max of 160 kJ/m3. [ABSTRACT FROM AUTHOR]

High-purity ternary Pr13Fe80B7 magnetic powder with high anisotropy is obtained by a modified hydrogenation disproportionation desorption recombination (HDDR) process in this work. This powder exhibits a record-high Br of 1.05 T, and has a good crystal texture along the c axis. It is found that the formation of HDDR Pr13Fe80B7 anisotropy is related to a rodlike disproportionation microstructure. We also show that by changing the HDDR conditions, an intrinsic coercivity of 800 kA/m and an energy product of 144 kJ/m3 are obtained on this powder. The details of the modified HDDR process are also presented in this paper. [ABSTRACT FROM AUTHOR]

We introduce the concept of quasi-hyperalgebraic lattice and prove that a complete lattice is a Priestley space with respect to the interval topology if and only if it is quasi-hyperalgebraic. Some characterizations of quasi-hyperalgebraic lattices are presented. We also prove that the Smyth powerdomain of a quasi-hyperalgebraic lattice is hyperalgebraic. [ABSTRACT FROM AUTHOR]

To investigate the process of strain relaxation and resultant variation of microstructure and magnetic properties, low-doped La0.825Sr0.175MnO3 epitaxial films with different thicknesses are deposited on LaAlO3 substrates and strain induced nanopillars are discovered inside the La0.825Sr0.175MnO3 film. Perpendicular oriented nanopillars mainly exist below 30 nm and tend to disappear above 30 nm. The distribution of nanopillars not only induce the variation of lattice parameters and local structural distortion but also lead to the deviation of easy magnetization axis from the perpendicular direction. Specifically, the out-of-plane lattice parameters of the film decrease quickly with the increase of the thickness but tend to be constant when the thickness is above 30 nm. Meanwhile, the variations of magnetic properties along in-plane and out-of-plane directions would also decline at first and they then remain nearly unchanged. Our work constructs the relationship between nanopillars and magnetic properties inside films. We are able to clearly reveal the effects of inhomogeneous strain relaxation. [ABSTRACT FROM AUTHOR]

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. [ABSTRACT FROM AUTHOR]

The evolution of a magnetic domain structure induced by temperature and magnetic field is reported in silicon-doped yttrium iron garnet (YIG) films with perpendicular anisotropy. During a cooling-down procedure from 300 K to 7 K, a 20% change in the domain width is observed, with the long tails of the stripes being shortened and the twisting stripes being straightened. Under the influence of the stray field of a barium ferrite, the garnet presents an interesting domain structure, which shows an appearance of branching protrusions. The intrinsic mechanisms in these two processes are also discussed. [ABSTRACT FROM AUTHOR]

The corrected Stefan—Boltzmann law of black holes in the frame of a generalized uncertainty principle is derived through the Planck equation of thermal radiation. The result is different from the flat spacetime: a corrected T6 term induced by the generalized uncertainty principle emerges; the coefficient of the T4 term is no longer a constant while related with the spacetime in the vicinity of the event horizon and the thin film model. Applying this corrected law to black hole radiation, the highest temperature in the final time of the radiation and the corresponding remnant with a mass of order of Planck mass are obtained. The lifespan of black holes is also corrected, however, the correction is extremely small. [ABSTRACT FROM AUTHOR]