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Due to the intensive development of novel biopharming applications, there is a need for the in vitro verification models prior to in vivo testing. Laying hen has been already applied as an animal bioreactor to produce the therapeutical enzyme in a rare disease called lysosomal acid lipase deficiency. In this study, we aimed to verify how the proteome of the transfected oviduct epithelial cells would be affected by genetic nonviral modification with the human exogene. The study was based on a previously developed method to cultivate chicken oviduct epithelial cells (COEC). The typical characteristics of the COEC epithelial cells were retained across the experiments. The mean efficiency of nucleofection ranged from 2.6 to 19.7% depending on the cells' isolation and location in the oviduct (upper, infundibulum site, or magnum). The PCR confirmed the incorporation of human interferon alpha2a ( hIFNα2a ) exogene into the nucleofected COEC but, the production of hIFNα2a protein did not exceed the detection level in this study. The ovalbumin protein was detected in the nontransfected and transfected COEC, which confirmed the normal secreting functions of the cells subject to modification. Proteomic analysis revealed an increase in abundance of the cell adhesion molecules and collagen molecules after introducing gene under ovalbumin promoter. According to the bioinformatic analyses there was a limited negative impact of transfection on cells, and the normal biochemical pathways were not severely disordered. In conclusion, the observations provide new knowledge about the proteomic profile of the manipulated COEC with regard to the retained normal functionality of the cells, which can be informative for avian biopharma research. [ABSTRACT FROM AUTHOR]

Immersed tube tunnel has been widely used in virtue of its characteristics of shallow burial, good waterproof performance, strong stratum adaptability, etc., however, it is also characterized by enclosed space, prolonged submersion of structure in deep water, complicated surrounding environment, etc., particularly, in case of accident of tunnel structure, inestimable losses will be caused, therefore, the control of structural stability risk in operation period is especially important. This article carries out risk source analysis and identification, scenario design and simulation analysis, risk loss judgment standards and weight research for structural stability of long and large immersed tube tunnel in operation period on basis of extra-large immersed tube tunnel of the fourth lane of Shenzhen-Zhongshan Thoroughfare, based on which and in combination with the relevant domestic and foreign risk assessment and expert research results, the structural stability risk levels and risk scores of structural stability in operation period are obtained by quantitative risk calculation method and the relevant suggestions for risk control are proposed. [ABSTRACT FROM AUTHOR]

Abstract: Chewing the areca nut is carcinogenic to humans. Arecoline, a major alkaloid in areca nut, is suspected to be a carcinogenic component. It has been shown to have genotoxic potential in various in vitro systems; but information on its in vivo genotoxicity is limited. To investigate the organ-specific mutagenic potential of arecoline, we employed gpt delta transgenic mice to analyze the mutagenicity of arecoline in the oral tissues and liver. Male gpt delta mice were given arecoline hydrobromide in drinking water at 300 and 700μg/mL for 6 weeks. 4-Nitroquinoline-1 (4-NQO) was used as a positive control. Two weeks after the last treatment, mutation frequencies in the oral tissues (a mixture of gingival, buccal, pharyngeal and sublingual tissue) and liver were detected and mutation spectra were analyzed. There were no statistically significant differences in the average mutation frequencies between arecoline-treated and untreated groups in both the oral tissues and liver. However, in the oral tissues, one mouse in arecoline-300μg/mL group and two mice in arecoline-700μg/mL group showed more than 2.5-fold higher mutation frequencies than the untreated group; they also exhibited unique mutation spectra compared to spontaneous mutation types. In these three mice, all mutations occurred at G:C sites, where G:C→T:A transversions were most frequent, followed by G:C→A:T transitions and G:C→C:G transversions. The main type of spontaneous mutation in both the oral tissues and liver was G:C→A:T transition. These results suggest that arecoline poses a mutagenic hazard in the oral tissues of gpt delta transgenic mice. [Copyright &y& Elsevier]

Stem and progenitor cells have the capacity to balance self-renewal and differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection. At what point along the spectrum of maturation do progenitors lose capacity for self-renewal and become irreversibly committed to differentiation? Using a system of conditional myeloid development that can be toggled between self-renewal and differentiation, we interrogate determinants of this "point of no return" in differentiation commitment. Irreversible commitment is due primarily to loss of open regulatory site access and disruption of a positive feedback transcription factor activation loop. Restoration of the transcription factor feedback loop extends the window of cell plasticity and alters the point of no return. These findings demonstrate how the chromatin state enforces and perpetuates cell fate and identify potential avenues for manipulating cell identity. [Display omitted] • There exists a point of irreversible commitment in granulocytic differentiation • Chromatin-state dynamics establish the transition from self-renewal to differentiation • Reduced chromatin accessibility underlies irreversible loss of regulatory site access • Restoration of a transcription factor feedback loop alters differentiation commitment Blanco et al. investigate the balance between self-renewal and differentiation and the mechanism of irreversible cell fate commitment. Using a model of conditional myeloid development, they find that loss of accessible chromatin and disruption of a transcription factor feedback loop underlies the "point of no return" in terminal myeloid differentiation. [ABSTRACT FROM AUTHOR]

Pluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 impairs mouse ESC differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1 −/− cells abnormally express developmental genes usually repressed by PRC2. Such de-repression is paralleled by decreased PRC2 binding to chromatin and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1 −/− cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins. • Depletion of ZFC3H1 in mouse ESCs results in differentiation defects • PRC2 target genes are deregulated in Zfc3h1 −/− cells • Chromatin binding of PRC2 and H3K27me3 is reduced in Zfc3h1 −/− cells • Increased binding of RNA impairs PRC2 complex stability ZFC3H1 targets pA+ RNA for decay by the nuclear RNA exosome. Garland et al. report a disruptive relationship between excess RNA and PRC2 upon depletion of ZFC3H1 in mouse ESCs. In such conditions, RNA is bound by PRC2 components, which show reduced binding to chromatin and fellow PRC2 proteins. [ABSTRACT FROM AUTHOR]

Two new polyketides versicolorones A-B (1 – 2), one new diketopiperazine derivative aspergiamide B methyl ester (3), along with twenty known compounds 4 – 23 , were obtained from the EtOAc extract of the Cordyceps -colonizing fungus Aspergillus versicolor ZJUTE2. The structures of 1 – 3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the calculated and experimental ECD spectra. In the in-vitro bioassay, compounds 8 and 21 exhibited significant inhibitory activity against the Escherichia coli β -glucuronidase (EcGUS) with IC 50 values of 54.73 ± 2.69 and 56.59 ± 1.77 μM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

Herein, the magnetocaloric effect (MCE) of Fe-doped Gd-rich microwires has been investigated. Experimental results indicated that this type of the microwires has entirely amorphous microstructure and smooth surface, and exhibits a relatively higher Curie temperature (∼121.8 K) as for the appropriate Fe substitution, and a remarkable and reversible MCE effect with almost no thermal or magnetic hysteresis loss. For a magnetic field change of 5 T, the isothermal magnetic entropy change (-Δ S m ) for the longitudinal direction reaches as large as 10.33 J kg −1 K −1 , besides the refrigerant capacity (RC) achieves a relatively large value of 748.22 J kg −1 . Meanwhile, the Arrott plots also indicate that the ferromagnetic-paramagnetic transition is of the second-order. Therefore, it can be concluded that the obtained Fe-doped Gd-rich wires are used as intelligent materials with enhanced MCE property for potential multifunctional applications in magnetic refrigeration field. [ABSTRACT FROM AUTHOR]

In recent years, polar topological textures like skyrmions and vortices in ferroelectric superlattices and multilayers have received extensive attention. However, the polar topological textures in these systems suffer strong interactions and are difficult to be manipulated as individual elements, limiting their application prospects in storage and logic devices. Here, via phase field simulations, we demonstrate domain engineering as a feasible strategy to create diverse weakly correlated polar topological texture arrays in single-layer tetragonal ferroelectric thin films, including Néel-type skyrmions with positive/negative topological charges and Bloch-type skyrmions with different chirality. We calculate the stability phase diagram and reveal the evolution characteristics of these polar topological textures under local electric and mechanical stimuli. We realize local erasing and writing of single Néel- and Bloch-type skyrmions, as well as deterministic chirality control of single Bloch-type skyrmion, confirming the weak correlation of the polar skyrmions. Our study therefore demonstrates domain engineering as an effective strategy for stabilizing weakly correlated polar topological textures, which extends the existence system of polar topological textures and paves a new way for the design of storage and logic devices based on polar topological textures. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] Tanshinone I facilitated the metabolism of AAI and reduced AAN. [•] Tanshinone I induced liver CYP1A expression. [•] Tanshinone I similarly increased the transcriptional activity of CYP1A1 and 1A2. [ABSTRACT FROM AUTHOR]

Unlabelled Image [ABSTRACT FROM AUTHOR]