The MST/YAP (mammalian Ste20-like kinase/Yes-associated protein 2) pathway plays an important role in hepatocellular carcinoma (HCC). Although post-translational modification-especially MST/Lats (large tumor suppressor)-mediated phosphorylation and PP1 (protein phosphatase-1)-mediated dephosphorylation-has been found to regulate the activity of YAP2, very little is known about its acetylation. In our experiments, we observed that the expression of SIRT1 is significantly upregulated in the tumor samples of the hepatocarcinoma patients, and SIRT1 mRNA level positively correlates with connective tissue growth factor (CTGF) mRNA level. We then found that SIRT1 deacetylates YAP2 protein in HCC cells and SIRT1-mediated deacetylation increases the YAP2/TEAD4 association, leading to YAP2/TEAD4 transcriptional activation and upregulated cell growth in HCC cells. Moreover, knockdown of SIRT1 blocks the cisplatin (CDDP)-induced nuclear translocation of YAP2 and enhances the chemosensitivity of HCC cells to CDDP treatment. Together, our findings reveal a new regulatory mechanism of YAP2 by the SIRT1-mediated deacetylation that may be involved in HCC tumorigenesis and drug resistance.
Summary In the field, the growth of the aquatic weed Eichhornia crassipes and the alga Microcystis aeruginosa may be inhibited by fallen leaves of Lantana camara. This study showed that extracts of L. camara leaves and their fractions reduced the biomass of E. crassipes and M. aeruginosa within 7 days under laboratory conditions. Two fractions with highly inhibitory activity from the extract were isolated and subsequently identified as the pentacyclic triterpenoids, lantadene A and lantadene B. Both compounds significantly inhibited E. crassipes and M. aeruginosa growth, even at a low concentration. At all concentrations tested, their inhibitory activities were much higher than that of salicylic acid, a putative allelochemical from L. camara. The results indicated that the predominant allelochemicals involved in L. camara against either E. crassipes or M. aeruginosa are not phenolic acids, but lantadene A and lantadene B. Field trials showed that released levels of lantadene A and lantadene B were significantly correlated with amounts and decomposition periods of L. camara leaves floated in water. The amount released from 5 kg L. camara leaves was over the inhibition threshold of both E. crassipes and M. aeruginosa and reached a maximum at days 15–20. This study suggested that allelochemicals of L. camara could potentially be used to improve the management of weeds and algae in aquatic systems.
Autotoxicity is a major reason for replant problems in managed tree ecosystems. Studies have related phenolics-based allelochemicals to autotoxicity. We selected a 20-year-old replanted Chinese fir [Cunninghamia lancealata (Lamb.) Hook] tree ecosystem to isolate, identify, determine the biological activity of, and quantify soil phytotoxins. Eight common phenolics (coumarin, vanillin, isovanillin, and p-hydroxybenzoic, vanillic, benzoic, cinnamic, and ferulic acids), friedelin, and a novel cyclic dipeptide (6-hydroxy-1,3-dimethyl-8-nonadecyl-[1,4]-diazocane-2,5-diketone) were obtained by using the bioassay-guided isolation technique from toxic soil of the replanted Chinese fir tree ecosystem. Chemical structures were determined by spectroscopic means, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) experiments. High concentrations of soil phenolics and friedelin were observed in the natural evergreen broadleaf forest (CK) rather than in the Chinese fir tree ecosystem. The phenolics and friedelin were not phytotoxic to Chinese fir trees. However, the cyclic dipeptide inhibited Chinese fir growth at soil concentrations determined in the replanted Chinese fir tree ecosystem. There was a significantly higher soil concentration of cyclic dipeptide in the replanted Chinese fir tree ecosystem than in a fresh Chinese fir tree ecosystem. The results suggest that phenolics and friedelin are not key allelochemicals since they are weakly phytotoxic and are detected in low concentrations in the replanted Chinese fir tree ecosystem, while cyclic dipeptide is a highly active allelochemical with a phytotoxic effect that limits offspring growth in the replanted Chinese fir tree ecosystem. The discovery of cyclic dipeptide, as well as a further understanding of its potential action mechanism in the replanted Chinese fir tree ecosystem, may contribute to solving the replant problems in managed tree ecosystems.
We report the follow-up of 10 pulsars discovered by the Five-hundred-meter Aperture Spherical radio-Telescope (FAST) during its commissioning. The pulsars were discovered at a frequency of 500-MHz using the ultra-wide-band (UWB) receiver in drift-scan mode, as part of the Commensal Radio Astronomy FAST Survey (CRAFTS). We carried out the timing campaign with the 100-m Effelsberg radio-telescope at L-band around 1.36 GHz. Along with 11 FAST pulsars previously reported, FAST seems to be uncovering a population of older pulsars, bordering and/or even across the pulsar death-lines. We report here two sources with notable characteristics. PSR J1951+4724 is a young and energetic pulsar with nearly 100 per cent of linearly polarized flux density and visible up to an observing frequency of 8 GHz. PSR J2338+4818, a mildly recycled pulsar in a 95.2-d orbit with a Carbon-Oxygen white dwarf (WD) companion of $\gtrsim 1\, \rm {M}_{\odot }$, based on estimates from the mass function. This system is the widest WD binary with the most massive companion known to-date. Conspicuous discrepancy was found between estimations based on NE2001 and YMW16 electron density models, which can be attributed to under-representation of pulsars in the sky region between Galactic longitudes 70○ < l < 100○. This work represents one of the early CRAFTS results, which start to show potential to substantially enrich the pulsar sample and refine the Galactic electron density model.
We report the phase-connected timing ephemeris, polarization pulse profiles, Faraday rotation measurements, and Rotating-Vector-Model (RVM) fitting results of twelve millisecond pulsars (MSPs) discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in the Commensal radio Astronomy FAST survey (CRAFTS). The timing campaigns were carried out with FAST and Arecibo over three years. Eleven of the twelve pulsars are in neutron star - white dwarf binary systems, with orbital periods between 2.4 and 100 d. Ten of them have spin periods, companion masses, and orbital eccentricities that are consistent with the theoretical expectations for MSP - Helium white dwarf (He WD) systems. The last binary pulsar (PSR J1912−0952) has a significantly smaller spin frequency and a smaller companion mass, the latter could be caused by a low orbital inclination for the system. Its orbital period of 29 days is well within the range of orbital periods where some MSP - He WD systems have shown anomalous eccentricities, however, the eccentricity of PSR J1912−0952 is typical of what one finds for the remaining MSP - He WD systems.
The follow-up timing observations were carried out for 24 pulsars discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey (CRAFTS). We report their phase-connected timing ephemeris, polarization pulse profiles and Faraday rotation measurements. With their spin periods spanning from 2.995 ms to 4.34 s, their period derivative were determined to spread between 7.996(8) × 10−21 s/s and 9.83(3) × 10−15 s/s, which imply that they have characteristic ages from 1.97 × 106 yr to 5.93 × 109 yr. It is inferred that PSRs J0211+4235 and J0518+2431 are beyond the ‘traditional death line’. PSR J0211+4235 is beyond the ‘death valley’. The death line model of Zhang et al (2000) also cannot explain the radio presence of PSR J0211+4235. This suggests that radiation theory needs to be improved. Besides, ten of the 22 canonical pulsars show nulling phenomena. Moreover, PSR J1617+1123 exhibits variation of emission and J0540+4542 shows subpulse drifting. The DM of five pulsars is larger than the estimated by the YMW16 electron density model, which could suggest that electron density models need updates for higher Galactic latitude regions. PSRs J0447+2447 and J1928−0548 are isolated millisecond pulsars. With their flux densities spanning from 5(1) μJy – 553(106) μJy, some of these new pulsars found by FAST are distant, dim, and low-$\dot{E}$ ones and are suitable for testing pulsar emission theories.
In the version of this article initially published, an equal-contributor footnote was missing for authors H. Xu, J. R. Niu and P. Chen. The Author contributions section has been amended to read "H.X., J.R.N. and P.C. contributed equally and led the data analysis". The changes have been made to the HTML and PDF versions of the article.
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