Anti-Hepatitis B Virus Effect and Possible Mechanism of Action of 3,4-O-Dicaffeoylquinic Acid In Vitro and In Vivo

The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 μg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 μg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression

Targeted next-generation sequencing of dedifferentiated chondrosarcoma in the skull base reveals combined TP53 and PTEN mutations with increased proliferation index, an implication for pathogenesis

Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Patient 1 exclusively exhibited a noncartilaginous component with a TP53 frameshift mutation in the pathological specimens from the first surgery. The tumor recurred after radiation therapy with an exceedingly increased proliferation index. Targeted next-generation sequencing (NGS) revealed the presence of both a TP53 mutation and a PTEN deletion in the cartilaginous and the noncartilaginous components of the recurrent tumor. Fluorescence in situ hybridization and immunostaining confirmed reduced DNA copy number and protein levels of the PTEN gene as a result of the PTEN deletion. Patient 2 exhibited both cartilaginous and noncartilaginous components in the surgical specimens. Targeted NGS of cells from both components showed neither TP53 nor PTEN mutations, making Patient 2 a naïve TP53 and PTEN control for comparison. In conclusion, additional PTEN loss in the background of the TP53 mutation could be the cause of increased proliferation capacity in the recurrent tumor

p21WAF1 and hypoxia/reoxygenation-induced premature senescence of H9c2 cardiomyocytes

We have previously reported on hypoxia/reoxygenation-induced premature senescence in neonatal rat cardiomyocytes. In this research, we investigated the effects of p21WAF1 (p21) in hypoxia/reoxygenation-induced senescence, using H9c2 cells. A plasmid overexpressing wild type p21WAF1 and a plasmid expressing small hairpin RNA (shRNA) targeting p21WAF1 were constructed, and transfected into H9c2 cells to control the p21 expression. Hypoxia/reoxygenation conditions were 1% O2 and 5% CO2, balancing the incubator chamber with N2 for 6 h (hypoxia 6 h), then 21% oxygen for 8 h (reoxygenation 8 h). Cell cycle was examined using flow cytometry. Senescence was assessed using β-galactosidase staining. The expression of p53, p21, p16INK4a, and cyclin D1 was assayed using Western blotting. At hypoxia 6 h, cells overexpressing p21 had a larger G1 distribution, stronger β-galactosidase activity, and lower cyclin D1 expression compared to control cells, while the opposite results and higher p53 expression were obtained in p21-knockdown cells. At reoxygenation 8 h, p21-silenced cells had a smaller percentage of G1 cells, weaker β-galactosidase activity and lower 16INK4a expression, and higher cyclin D1 expression, but the overexpression group showed no difference. Taken together, this data implies that p21WAF1 is important for the hypoxia phase, but not the reoxygenation phase, in the H9c2 senescence process. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 445–451

SkillNet-X: A Multilingual Multitask Model with Sparsely Activated Skills

Traditional multitask learning methods basically can only exploit common knowledge in task- or language-wise, which lose either cross-language or cross-task knowledge. This paper proposes a general multilingual multitask model, named SkillNet-X, which enables a single model to tackle many different tasks from different languages. To this end, we define several language-specific skills and task-specific skills, each of which corresponds to a skill module. SkillNet-X sparsely activates parts of the skill modules which are relevant either to the target task or the target language. Acting as knowledge transit hubs, skill modules are capable of absorbing task-related knowledge and language-related knowledge consecutively. Based on Transformer, we modify the multi-head attention layer and the feed forward network layer to accommodate skill modules. We evaluate SkillNet-X on eleven natural language understanding datasets in four languages. Results show that SkillNet-X performs better than task-specific baselines and two multitask learning baselines (i.e., dense joint model and Mixture-of-Experts model). Furthermore, skill pre-training further improves the performance of SkillNet-X on almost all datasets. To investigate the generalization of our model, we conduct experiments on two new tasks and find that SkillNet-X significantly outperforms baselines

LAMOST observations in the Kepler field. Analysis of the stellar parameters measured with the LASP based on the low-resolution spectra

All of the 14 subfields of the Kepler field have been observed at least once with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, Xinglong Observatory, China) during the 2012-2014 observation seasons. There are 88,628 reduced spectra with SNR$_g$ (signal-to-noise ratio in g band) $\geq$ 6 after the first round (2012-2014) of observations for the LAMOST-Kepler project (LK-project). By adopting the upgraded version of the LAMOST Stellar Parameter pipeline (LASP), we have determined the atmospheric parameters ($T_{\rm eff}$ , $\log g$, and $\rm [Fe/H]$) and heliocentric radial velocity $v_{\rm rad}$ for 51,406 stars with 61,226 spectra. Compared with atmospheric parameters derived from both high-resolution spectroscopy and asteroseismology method for common stars in Huber et al. (2014), an external calibration of LASP atmospheric parameters was made, leading to the determination of external errors for the giants and dwarfs, respectively. Multiple spectroscopic observations for the same objects of the LK-project were used to estimate the internal uncertainties of the atmospheric parameters as a function of SNR$_g$ with the unbiased estimation method. The LASP atmospheric parameters were calibrated based on both the external and internal uncertainties for the giants and dwarfs, respectively. A general statistical analysis of the stellar parameters leads to discovery of 106 candidate metal-poor stars, 9 candidate very metal-poor stars, and 18 candidate high-velocity stars. Fitting formulae were obtained segmentally for both the calibrated atmospheric parameters of the LK-project and the KIC parameters with the common stars. The calibrated atmospheric parameters and radial velocities of the LK-project will be useful for studying stars in the Kepler field.Comment: 53 pages, 21 figures, 5 tables, Accepted for publication by ApJ

[Amino­(iminio)meth­yl]phospho­nate

The title compound, CH5N2O3P, exists as a zwitterion. The N atom of the imino group is protonated and the phospho­nic acid group is deprotonated. The mol­ecular geometry about the central C atom of this zwitterionic species was found to be strictly planar with the sum of the three angles about C being precisely 360°. In the crystal, the mol­ecules are inter­linked by O—H⋯O and N—H⋯O hydrogen-bonding inter­actions, forming a three-dimensional supra­molecular network structure

Biobutanol production in a Clostridium acetobutylicum biofilm reactor integrated with simultaneous product recovery by adsorption

BACKGROUND: Clostridium acetobutylicum can propagate on fibrous matrices and form biofilms that have improved butanol tolerance and a high fermentation rate and can be repeatedly used. Previously, a novel macroporous resin, KA-I, was synthesized in our laboratory and was demonstrated to be a good adsorbent with high selectivity and capacity for butanol recovery from a model solution. Based on these results, we aimed to develop a process integrating a biofilm reactor with simultaneous product recovery using the KA-I resin to maximize the production efficiency of biobutanol. RESULTS: KA-I showed great affinity for butanol and butyrate and could selectively enhance acetoin production at the expense of acetone during the fermentation. The biofilm reactor exhibited high productivity with considerably low broth turbidity during repeated batch fermentations. By maintaining the butanol level above 6.5 g/L in the biofilm reactor, butyrate adsorption by the KA-I resin was effectively reduced. Co-adsorption of acetone by the resin improved the fermentation performance. By redox modulation with methyl viologen (MV), the butanol-acetone ratio and the total product yield increased. An equivalent solvent titer of 96.5 to 130.7 g/L was achieved with a productivity of 1.0 to 1.5 g · L(-1) · h(-1). The solvent concentration and productivity increased by 4 to 6-fold and 3 to 5-fold, respectively, compared to traditional batch fermentation using planktonic culture. CONCLUSIONS: Compared to the conventional process, the integrated process dramatically improved the productivity and reduced the energy consumption as well as water usage in biobutanol production. While genetic engineering focuses on strain improvement to enhance butanol production, process development can fully exploit the productivity of a strain and maximize the production efficiency