Prunella vulgaris: A comprehensive review of chemical constituents, pharmacological effects and clinical applications.

Prunella vulgaris (PV) is a perennial herb belonging to the Labiate family and is widely distributed in northeastern Asian countries such as Korea, Japan, and China. It is reported to display diverse biological activities including anti-microbial, anti-cancer, and anti-inflammation as determined by in vitro or in vivo studies. So far, about 200 compounds have been isolated from PV plant and majority of these have been characterized mainly as triterpenoids, sterols and flavonoids, followed by coumarins, phenylpropanoids, polysaccharides and volatile oils. This review summarizes and analyzes the current knowledge on the chemical constituents, pharmacological activities, mechanisms of action and clinical applications of the PV plant including its potential as a future medicinal plant. Although some of the chemical constituents of the PV plant and their mechanism of action have been investigated the biological activities of many of these remain unknown and further clinical trials are required to further enhance its reputation as a medicinal plant

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

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

(−)-Naringenin 4′,7-dimethyl Ether Isolated from <i>Nardostachys jatamansi</i> Relieves Pain through Inhibition of Multiple Channels

(−)-Naringenin 4′,7-dimethyl ether ((−)-NRG-DM) was isolated for the first time by our lab from Nardostachys jatamansi DC, a traditional medicinal plant frequently used to attenuate pain in Asia. As a natural derivative of analgesic, the current study was designed to test the potential analgesic activity of (−)-NRG-DM and its implicated mechanism. The analgesic activity of (−)-NRG-DM was assessed in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model, in which the mice were intraperitoneally administrated with vehicle or (−)-NRG-DM (30 or 50 mg/kg) (n = 10 for each group). Our data showed that (−)-NRG-DM can dose dependently (30~50 mg/kg) relieve the pain behaviors. Notably, (−)-NRG-DM did not affect motor coordination in mice evaluated by the rotarod test, in which the animals were intraperitoneally injected with vehicle or (−)-NRG-DM (100, 200, or 400 mg/kg) (n = 10 for each group). In acutely isolated mouse dorsal root ganglion neurons, (−)-NRG-DM (1~30 μM) potently dampened the stimulated firing, reduced the action potential threshold and amplitude. In addition, the neuronal delayed rectifier potassium currents (IK) and voltage-gated sodium currents (INa) were significantly suppressed. Consistently, (−)-NRG-DM dramatically inhibited heterologously expressed Kv2.1 and Nav1.8 channels which represent the major components of the endogenous IK and INa. A pharmacokinetic study revealed the plasma concentration of (−)-NRG-DM is around 7 µM, which was higher than the effective concentrations for the IK and INa. Taken together, our study showed that (−)-NRG-DM is a potential analgesic candidate with inhibition of multiple neuronal channels (mediating IK and INa)

Albumin Fusion at the N-Terminus or C-Terminus of HM-3 Leads to Improved Pharmacokinetics and Bioactivities

HM-3, an integrin antagonist, exhibits anti-tumor biological responses and therefore has potential as a therapeutic polypeptide. However, the clinical applications of HM-3 are limited by its short half-life. In this study, we genetically fused human serum albumin (HSA) to the N or C-terminus of HM-3 to improve HM-3 pharmacokinetics. HM-3/HSA proteins were successfully expressed in Pichia pastoris and displayed improved pharmacokinetic properties and stability. Among them, the half-life of HM-3-HSA was longer than HSA-HM-3. In vitro, the IC50 values of HSA-HM-3 and HM-3-HSA were 0.38 ± 0.14 μM and 0.25 ± 0.08 μM in B16F10 cells, respectively. In vivo, the inhibition rates of B16F10 tumor growth were 36% (HSA-HM-3) and 56% (HM-3-HSA), respectively, indicating antitumor activity of HM-3-HSA was higher than HSA-HM-3. In conclusion, these results suggested that the HM-3/HSA fusion protein might be potential candidate HM-3 agent for treatment of melanoma and when HSA was fused at the C-terminus of HM-3, the fusion protein had a higher stability and activity

Research Progresses in Improvement for Low Temperature Performance of Lithium-Ion Batteries

锂离子电池因其能量密度高，循环寿命长等优点已成为新型动力电池领域的研究热点，但其温度特性尤其是低温性能较差制约着锂离子电池的进一步使用. 本文综述了锂离子电池低温性能的研究进展，系统地分析了锂离子电池低温性能的主要限制因素. 从正极、电解液、负极三个方面讨论了近年来研究者们提高电池低温性能的改性方法. 并对提高锂离子电池低温性能的发展方向进行了展望.Lithium-ion batteries (LIBs) have become a new research hotspot due to their high energy density and long service life. However, the temperature characteristics, especially the poor performance at low temperatures, have seriously limited their wider applications. In this report, the research progresses in the low temperature performance of LIBs are reviewed. The main existing limitations of LIBs at low temperatures were systematically analyzed, and followed by discussion on the recent improvements in low temperature performances by developing novel cathode, electrolyte, and anode materials. The developments for improving the low temperature performance of LIBs are prospected. The three most important factors that influence the low temperature electrochemical performance of LIBs are as follows: 1) a reduced ion conductivity of the electrolyte and solid electrolyte interface (SEI) film formed on the electrode/electrolyte interface; 2) increased charge-transfer resistances at both the cathode and anode electrolyte- electrode interfaces; 3) slow lithium diffusion in the electrodes. The above three points lead to high polarization and lithium deposition, which may cause problems in terms of performance, reliability and safety of the cell. The key point is to provide expedite paths for the transport of lithium ions and electrons at low temperatures. All the influential aspects, such as cathode, electrolyte,and anode, should be considered to improve the low temperature performance of LIBs. The low temperature electrolyte can be obtained by adjusting the relative compositions, and species of the solvent, salt, and additive. The conductivity of electrolyte can be improved by adding low melting point cosolvents and salts. In addition, use of electrolyte additives forming low impedance interface film is one of the most economic and effective methods to improve the low temperature performance. And the structure of electrode materials can be optimized by doping, coating and decreasing the particle size, which can ensure sufficient conductivity and shorten diffusion path length for lithium ions and electrons. Managing the electrolyte and developing electrodes are efficient methods to improve the low temperature performance. Future studies should be focused on achieving high performance lithium-ion battery materials.国家重点研发计划（No. 2018YFB010400）和福建省高校产学合作项目（No. 2018H6020）资助作者联系地址：1.多氟多化工股份有限公司，河南 焦作 454150; 2. 厦门大学化学化工学院/能源学院，福建 厦门 361005; 3. 多氟多(焦作)新能源科技有限公司，河南 焦作454150Author's Address: 1. Do-fluoride Chemicals Co., Ltd, Jiaozuo 454150, Henan, China; 2. College of Chemistry and Chemical Engineering/College of energy, Xiamen University, Xiamen 361005, Fujian China 3. Do-Fluoride Jiaozuo New Energy Technology CO., Ltd, Jiaozuo 454150, Henan, China通讯作者E-mail：[email protected]; yyang@xmu. edu. c