Exploring the active mechanism of berberine against HCC by systematic pharmacology and experimental validation

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Berberine (BBR) is the main component of Coptidis rhizoma, the dried rhizome of Coptis chinensis and is a potential plant alkaloid used for the treatment of cancer due to its high antitumor activity. The present study examined the therapeutic potential and molecular mechanism of action of BBR against HCC, using systematic pharmacology combined with a molecular docking approach and experimental validation in vitro. Through systematic pharmacological analysis, it was found that BBR serves a significant role in inhibiting HCC by affecting multiple pathways, especially the PI3K/AKT signaling pathway. Furthermore, the docking approach indicated that the binding of BBR to AKT could lead to the suppression of AKT activity. The present study examined the inhibitory effect of BBR on the PI3K/AKT pathway in HCC and identified that BBR downregulated the expressions of phosphorylated AKT and PI3K in MHCC97‑H and HepG2 cells, inhibiting their growth, cell migration and invasion in a dose‑dependent manner. In addition, inhibition of the AKT pathway by BBR also contributed to cell apoptosis in MHCC97‑H and HepG2 cells. Taken together, the results of the present study suggested that BBR may be a promising antitumor drug for HCC that acts by inhibiting the PI3K/AKT pathway

LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild-type mice and Lrrk1-deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L-plastin, an actin bundling protein. We found that phosphorylation of L-plastin at serine (Ser) residues 5 was present in wild-type osteoclasts but not in Lrrk1-deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated L-plastin confirmed the reduced L-plastin Ser5 phosphorylation in Lrrk1 knockout (KO) osteoclasts. micro computed tomography (Micro-CT) analyses revealed that the trabecular bone volume of the distal femur was increased by 27% in the 16 to 21-week-old L-plastin KO females as compared with the wild-type control mice. The ratio of bone volume to tissue volume and connectivity density were increased by 44% and 47% (both P \u3c 0.05), respectively, in L-plastin KO mice. Our data suggest that targeted disruption of L-plastin increases trabecular bone volume, and phosphorylation of Ser5 in L-plastin in the Lrrk1 signaling pathway may in part contribute to actin assembly in mature osteoclasts

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Effect of Various Pretreatments on Quality Attributes of Vacuum-Fried Shiitake Mushroom Chips

The objective of this study is to investigate the effects of pretreatments on the quality of vacuum-fried shiitake mushroom slices. Four different pretreatments addressed in this study were (1) blanching as control, (2) blanching and osmotic dehydration with maltodextrin (MD) solution, (3) blanching, osmotic dehydration, and coating with sodium carboxymethyl cellulose (CMC), (4) blanching and osmotic dehydration, followed by freezing. All samples were pretreated and then fried in palm oil at 90°C with vacuum degree of −0.095 MPa for 30 min. The results showed that pretreatments significantly (p < 0.05) affected the moisture content, oil content, color, water activity aw, total phenolic content, and sensory evaluation of shiitake mushroom chips. The blanching, osmotic dehydration, and coating pretreatment could improve color and sensory evaluation and also minimize the oil uptake of fried chips, whereas this treatment caused the highest reduction of total phenolic contents. There were no significant (p > 0.05) differences of fried chip in the texture among the four different pretreatments. The aw values of all the fried chips were less than 0.38, indicating that the products had a long shelf life. Therefore, the blanching, osmotic dehydration, and coating pretreatment before vacuum frying was the most suitable pretreatment for vacuum-fried shiitake mushroom chips

Real-Time PPP Based on the Coupling Estimation of Clock Bias and Orbit Error with Broadcast Ephemeris

Satellite orbit error and clock bias are the keys to precise point positioning (PPP). The traditional PPP algorithm requires precise satellite products based on worldwide permanent reference stations. Such an algorithm requires considerable work and hardly achieves real-time performance. However, real-time positioning service will be the dominant mode in the future. IGS is providing such an operational service (RTS) and there are also commercial systems like Trimble RTX in operation. On the basis of the regional Continuous Operational Reference System (CORS), a real-time PPP algorithm is proposed to apply the coupling estimation of clock bias and orbit error. The projection of orbit error onto the satellite-receiver range has the same effects on positioning accuracy with clock bias. Therefore, in satellite clock estimation, part of the orbit error can be absorbed by the clock bias and the effects of residual orbit error on positioning accuracy can be weakened by the evenly distributed satellite geometry. In consideration of the simple structure of pseudorange equations and the high precision of carrier-phase equations, the clock bias estimation method coupled with orbit error is also improved. Rovers obtain PPP results by receiving broadcast ephemeris and real-time satellite clock bias coupled with orbit error. By applying the proposed algorithm, the precise orbit products provided by GNSS analysis centers are rendered no longer necessary. On the basis of previous theoretical analysis, a real-time PPP system was developed. Some experiments were then designed to verify this algorithm. Experimental results show that the newly proposed approach performs better than the traditional PPP based on International GNSS Service (IGS) real-time products. The positioning accuracies of the rovers inside and outside the network are improved by 38.8% and 36.1%, respectively. The PPP convergence speeds are improved by up to 61.4% and 65.9%. The new approach can change the traditional PPP mode because of its advantages of independence, high positioning precision, and real-time performance. It could be an alternative solution for regional positioning service before global PPP service comes into operation

Microstructure Evolution and Solidification Behavior of a Novel Semi-Solid Alloy Slurry Prepared by Vibrating Contraction Inclined Plate

In this work, based on the A356 alloy, a novel Al–Si–Mg–Cu–Fe–Sr alloy with good mechanical property and high thermal conductivity was developed. The semi-solid slurry of the alloy was prepared via the vibrating contraction inclined plate. The microstructure evolution and solidification behavior of the alloy were investigated. The results demonstrated that, compared with the A356 alloy, the enhanced property of the Al–Si–Mg–Cu–Fe–Sr alloy was associated with the size of primary α-Al grains and morphology of eutectic Si phases. In addition, the preparation process parameters of semi-solid slurries, including the pouring temperature, inclination angle, and vibration frequency, had a crucial effect on the size and morphology of primary α-Al grains. The optimized pouring temperature, inclination angle, and vibration frequency were 670 °C, 45°, and 60 Hz, respectively. In this condition, for the primary α-Al grains, a minimum grain diameter of 64.31 µm and a maximum shape factor of 0.80 were obtained. This work provides a reference for the application of the alloy with high performance in the field of automobile and communication

The role of national carbon pricing in phasing out China's coal power

Summary: As the country with the world's largest coal power capacity, China is launching a national carbon market. How the carbon pricing may contribute to phasing out China's coal power is a great concern. We collect full-sample data set of China's 4540 operating coal plant units and develop a stochastic Monte-Carlo financial model to assess the financial sustainability of the plant operation. Although China's coal plants have long residual technical lifetime, their operations are close to the break-even state. Even with low carbon price of 50 CNY/tCO2 growing at 4%/y and the permits being fully auctioned, the average residual lifetime of all the plants will be reduced by 5.43 years, and the cumulative CO2 emission from 2020 to 2050 will be reduced by 22.73 billion ton. The spatial disparity in the carbon pricing effect is significant, and the western regions are more vulnerable to the carbon pricing risk than the eastern regions