A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Methods In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. Results In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. Conclusions We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC

Distinct Biogeography of Different Fungal Guilds and Their Associations With Plant Species Richness in Forest Ecosystems

Plant pathogens are increasingly considered as important agents in promoting plant coexistence, while plant symbionts like ectomycorrhizal fungi (EMF) can facilitate plant dominance by helping conspecific individuals to defend against plant pathogens. However, we know little about their relationships with plants at large scales. Here, using soil fungal data collected from 28 forest reserves across China, we explored the latitudinal diversity gradients of overall fungi and different fungal functional guilds, including putative plant pathogens, EMF, and saprotrophic fungi. We further linked the spatial patterns of alpha diversities of putative plant pathogens and EMF to the variation of plant species richness. We found that the relationships between latitude and alpha diversities of putative plant pathogens and EMF were region-dependent with sharp diversity shifts around the mid-latitude (similar to 35 degrees N), which differed from the unimodal diversity distributions of the overall and saprotrophic fungi. The variations in the diversities of putative plant pathogens and EMF were largely explained by the spatial regions (south vs. north/subtropical zone vs. temperate zone). Additionally, the alpha diversities of these two fungal guilds exhibited opposing trends across latitude. EMF could alter the relationship between diversities of putative plant pathogens and plants in the south/subtropical region, but not vice versa. We also found that the ratio of their alpha diversities (EMF to putative plant pathogens) was negatively related to plant species richness across the spatial regions (north to south), and explained similar to 10% of the variation of plant species richness. Overall, our findings suggest that plant-microbe interactions not only shape the local plant diversity but also may have non-negligible contributions to the large-scale patterns of plant diversity in forest ecosystems.National Natural Science Foundation of China [31600403, 31800422, 41673111, U1501232, 41622106]; Natural Science Foundation of Guangdong Province, China [2016A030312003]; U.S. National Science Foundation MacroSystems Biology program [NSF EF-1065844]; Candidates at Sun Yat-Sen UniversityOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Kimura disease of submandibular gland : submandibular Kimura disease

Kimura disease (KD) is a rare benign chronic inflammatory disorder of unknown aetiology prevalence in young adult Asian males. Head and neck region especially salivary gland and cervical lymph node are the most commonly affected. In contrast to parotid gland, submandibular gland involvement is rarely reported. Diagnosis is always challenging due to variable presentations that may mimic other inflammatory or neoplastic conditions, and non-specific imaging, cytology, and histopathology findings. Generally, there was several treatments modality reported but showed variable response with high recurrence rate. The treatment for submandibular gland KD specifically is not well describe due to its rarity. We present a case of KD with submandibular gland and cervical lymph node involvement in elderly man that mimic malignancy and highlight the challenging in management.peer-reviewe

Genetic variation and recombination analysis of the GP5 (GP5a) gene of PRRSV-2 strains in China from 1996 to 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) has been prevalent in China for more than 25 years and remains one of the most significant pathogens threatening the pig industry. The high rate of mutation and frequent recombination of PRRSV have exacerbated its prevalence, particularly with the emergence of highly pathogenic PRRSV (HP-PRRSV) has significantly increased the pathogenicity of PRRSV, posing a serious threat to the development of Chinese pig farming. To monitor the genetic variation of PRRSV-2 in China, the GP5 sequences of 517 PRRSV-2 strains from 1996 to 2022 were analyzed and phylogenetic trees were constructed. Furthermore, a total of 60 PRRSV strains, originating from various lineages, were carefully chosen for nucleotide and amino acid homologies analysis. The results showed that the nucleotide homologies of the PRRSV GP5 gene ranged from 81.4 to 100.0%, and the amino acid homologies ranged from 78.1 to 100.0%. Similarly, the PRRSV GP5a gene showed 78.0 ~ 100.0% nucleotide homologies and 70.2 ~ 100.0% amino acid homologies. Amino acid sequence comparisons of GP5 and GP5a showed that some mutations, such as substitutions, deletions, and insertions, were found in several amino acid sites in GP5, these mutations were primarily found in the signal peptide region, two highly variable regions (HVRs), and near two T-cell antigenic sites, while the mutation sites of GP5a were mainly concentrated in the transmembrane and intramembrane regions. Phylogenetic analysis showed that the prevalent PRRSV-2 strains in China were divided into lineages 1, 3, 5, and 8. Among these, strains from lineage 8 and lineage 1 are currently the main prevalent strains, lineage 5 and lineage 8 have a closer genetic distance. Recombination analysis revealed that one recombination event occurred in 517 PRRSV-2 strains, this event involved recombination between lineage 8 and lineage 1. In conclusion, this analysis enhances our understanding of the prevalence and genetic variation of PRRSV-2 in China. These findings provide significant insights for the development of effective prevention and control strategies for PRRS and serve as a foundation for future research in this field

TOI-216b and TOI-216 c: Two Warm, Large Exoplanets in or Slightly Wide of the 2:1 Orbital Resonance

Warm, large exoplanets with 10-100 day orbital periods pose a major challenge to our understanding of how planetary systems form and evolve. Although high eccentricity tidal migration has been invoked to explain their proximity to their host stars, a handful reside in or near orbital resonance with nearby planets, suggesting a gentler history of in situ formation or disk migration. Here we confirm and characterize a pair of warm, large exoplanets discovered by the TESS Mission orbiting K-dwarf TOI-216. Our analysis includes additional transits and transit exclusion windows observed via ground-based follow-up. We find two families of solutions, one corresponding to a sub-Saturn-mass planet accompanied by a Neptune-mass planet and the other to a Jupiter in resonance with a sub-Saturn-mass planet. We prefer the second solution based on the orbital period ratio, the planet radii, the lower free eccentricities, and libration of the 2:1 resonant argument, but cannot rule out the first. The free eccentricities and mutual inclination are compatible with stirring by other, undetected planets in the system, particularly for the second solution. We discuss prospects for better constraints on the planets' properties and orbits through follow-up, including transits observed from the ground.We gratefully acknowledge support by NASA XRP NNX16AB50G and NASA TESS GO 80NSSC18K1695. The Center for Exoplanets and Habitable Worlds is supported by the Pennsylvania State University, the Eberly College of Science, and the Pennsylvania Space Grant Consortium. T.D. acknowledges support from MIT’s Kavli Institute as a Kavli postdoctoral fellow. K.H. acknowledges support from STFC grant ST/R000824/1. M.Ž. acknowledges funding from the Australian Research Council (grant DP170102233). This research was supported in part by the National Science Foundation under Grant No. NSF PHY-1748958

Stay in touch with the endoplasmic reticulum

The endoplasmic reticulum (ER), which is composed of a continuous network of tubules and sheets, forms the most widely distributed membrane system in eukaryotic cells. As a result, it engages a variety of organelles by establishing membrane contact sites (MCSs). These contacts regulate organelle positioning and remodeling, including fusion and fission, facilitate precise lipid exchange, and couple vital signaling events. Here, we systematically review recent advances and converging themes on ER-involved organellar contact. The molecular basis, cellular influence, and potential physiological functions for ER/nuclear envelope contacts with mitochondria, Golgi, endosomes, lysosomes, lipid droplets, autophagosomes, and plasma membrane are summarized.JH is supported by the National Natural Science Foundation of China (92254305), the Strategic Priority Research Program (XDB39000000) and Project for Young Scientists in Basic Research (YSBR-075) of the Chinese Academy of Sciences, and the National Key Research and Development Program of China (2021YFA1300800). CZ is supported by the National Natural Science Foundation of China (92254305, 91854204, 32130026). LG is supported by National Natural Science Foundation of China (92254302, 32225013, 32130023), National Key Research and Development Program of China (2021YFA0804802, 2019YFA0508602), Beijing Natural Science Foundation (JQ20028), and New Cornerstone Science Foundation (Xplorer Prize). HC is supported by grants from the National Natural Science Foundation of China (92254303, 32170701), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB37020304), and the National Key Research and Development Program of China (2021YFA1300301). GY is supported by the National Natural Science Foundation of China (91954201,31971289) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB37040402). XH is supported by grants from the National Natural Science Foundation of China (91954207), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA24030205), and the National Key Research and Development Program of China (2018YFA0506902). YGZ is supported by the National Natural Science Foundation of China (32170753). XB is supported by the National Natural Science Foundation of China (32170692, 92154001), the Fundamental Research Funds for the Central Universities (63213104, 63223043), and the Talent Training Project at Nankai University (035-BB042112). SS is supported by grants from the National Natural Science Foundation of China (32101000, 32271273). WL is supported by the Beijing Municipal Science & Technology Commission (5202022).Peer reviewe

The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project.Comment: This document is a collaborative effort, 185 pages, 110 figure

Genome editing of a rice CDP-DAG synthase confers multipathogen resistance

Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovatio

A Remnant Planetary Core In The Hot-Neptune desert

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune ‘desert’1,2 (a region in mass–radius space that contains few planets) have proved to be particularly valuable in this regard. These planets include HD149026b3, which is thought to have an unusually massive core, and recent discoveries such as LTT9779b4 and NGTS-4b5, on which photoevaporation has removed a substantial part of their outer atmospheres. Here we report observations of the planet TOI-849b, which has a radius smaller than Neptune’s but an anomalously large mass of 39.1+2.7−2.6 Earth masses and a density of 5.2+0.7−0.8 grams per cubic centimetre, similar to Earth’s. Interior-structure models suggest that any gaseous envelope of pure hydrogen and helium consists of no more than 3.9+0.8−0.9 per cent of the total planetary mass. The planet could have been a gas giant before undergoing extreme mass loss via thermal self-disruption or giant planet collisions, or it could have avoided substantial gas accretion, perhaps through gap opening or late formation6. Although photoevaporation rates cannot account for the mass loss required to reduce a Jupiter-like gas giant, they can remove a small (a few Earth masses) hydrogen and helium envelope on timescales of several billion years, implying that any remaining atmosphere on TOI-849b is likely to be enriched by water or other volatiles from the planetary interior. We conclude that TOI-849b is the remnant core of a giant planet