Functional division of the dorsal striatum based on a graph neural network

The dorsal striatum, an essential nucleus in subcortical areas, has a crucial role in controlling a variety of complex cognitive behaviors; however, few studies have been conducted in recent years to explore the functional subregions of the dorsal striatum that are significantly activated when performing multiple tasks. To explore the differences and connections between the functional subregions of the dorsal striatum that are significantly activated when performing different tasks, we propose a framework for functional division of the dorsal striatum based on a graph neural network model. First, time series information for each voxel in the dorsal striatum is extracted from acquired functional magnetic resonance imaging data and used to calculate the connection strength between voxels. Then, a graph is constructed using the voxels as nodes and the connection strengths between voxels as edges. Finally, the graph data are analyzed using the graph neural network model to functionally divide the dorsal striatum. The framework was used to divide functional subregions related to the four tasks including olfactory reward, "0-back" working memory, emotional picture stimulation, and capital investment decision-making. The results were further subjected to conjunction analysis to obtain 15 functional subregions in the dorsal striatum. The 15 different functional subregions divided based on the graph neural network model indicate that there is functional differentiation in the dorsal striatum when the brain performs different cognitive tasks. The spatial localization of the functional subregions contributes to a clear understanding of the differences and connections between functional subregions

Penetration and pharmacokinetics of ferulic acid after dermal administration

Purpose: To study the in vitro penetration and in vivo pharmacokinetics of ferulic acid (FA), and the correlation between them after dermal administration. Methods: Franz diffusion cell was used to study in vitro penetration of FA. The concentration of FA in the Franz receiver solution was assessed by high performance liquid chromatography (HPLC). Prior to in vivo pharmacokinetics experiments, probe recovery was validated with respect to influencing factors such as flow rate, FA concentration, within-day stability and reproducibility of the probes. In in vivo pharmacokinetic experiment, six male CD-1 hairless mice were used. The micro-dialysis (MD) probe was implanted in the dermis of the rat skin, and dialysates from probe outlet were quantified directly by HPLC. In in vivo studies, deconvolution methods were used to determine the relationship between in vitro and in vivo data, and the correlation coefficient of linear equations. Results: There was significant effect of pH (5 ~ 8) on the penetration of FA. Increase in pH caused commensurate decrease in permeability. The Cmax of FA was 300.74 ± 31.86 ng/mL while Tmax was 138.00 ± 22.80 min after dermal administration of 1 mg/mL FA dissolved in phosphate buffered saline (PBS). The correlation coefficient (r) between in vitro and in vivo data was 0.9905. Conclusion: Both in vivo and in vitro experiments demonstrate that FA permeates the stratum corneum of skin rapidly. The unionized form of FA shows better penetration than the ionic form. In addition, results from correlation analysis indicate that the in vitro penetration characteristics of FA can be applied to predict its in vivo pharmacokinetics

Combining Metabolomics and Transcriptomics to Characterize Tanshinone Biosynthesis in Salvia Miltiorrhiza

Plant natural products have been co-opted for millennia by humans for various uses such as flavor, fragrances, and medicines. These compounds often are only produced in relatively low amounts and are difficult to chemically synthesize, limiting access. While elucidation of the underlying biosynthetic processes might help alleviate these issues (e.g., via metabolic engineering), investigation of this is hindered by the low levels of relevant gene expression and expansion of the corresponding enzymatic gene families. However, the often-inducible nature of such metabolic processes enables selection of those genes whose expression pattern indicates a role in production of the targeted natural product. Here, we combine metabolomics and transcriptomics to investigate the inducible biosynthesis of the bioactive diterpenoid tanshinones from the Chinese medicinal herb, Salvia miltiorrhiza(Danshen). Untargeted metabolomics investigation of elicited hairy root cultures indicated that tanshinone production was a dominant component of the metabolic response, increasing at later time points. A transcriptomic approach was applied to not only define a comprehensive transcriptome (comprised of 20,972 non-redundant genes), but also its response to induction, revealing 6,358 genes that exhibited differential expression, with significant enrichment for up-regulation of genes involved in stress, stimulus and immune response processes. Consistent with our metabolomics analysis, there appears to be a slower but more sustained increased in transcript levels of known genes from diterpenoid and, more specifically, tanshinone biosynthesis. Among the co-regulated genes were 70 transcription factors and 8 cytochromes P450, providing targets for future investigation. Our results indicate a biphasic response of Danshen terpenoid metabolism to elicitation, with early induction of sesqui- and tri- terpenoid biosynthesis, followed by later and more sustained production of the diterpenoid tanshinones. Our data provides a firm foundation for further elucidation of tanshinone and other inducible natural product metabolism in Danshen

A fluorescent peptidyl substrate for visualizing peptidyl-prolyl cis/trans isomerase activity in live cells

Imaging active PPIases in live cells with a small molecular probe.</p

Two-Dimensional Platinum Telluride with Ordered Te Vacancy Superlattice for Efficient and Robust Hydrogen Evolution

Defect engineering to activate the basal planes of transition metal dichalcogenides (TMDs) is critical for the development of TMD-based electrocatalysts as the chemical inertness of basal planes restrict their potential applications in hydrogen evolution reaction (HER). Here, we report the synthesis and evaluation of few-layer (7x7)-PtTe2-x with an ordered, well-defined and high-density Te vacancy superlattice. Compared with pristine PtTe2, (2x2)-PtTe2-x and Pt(111), (7x7)-PtTe2-x exhibits superior HER activities in both acidic and alkaline electrolytes due to its rich structures of undercoordinated Pt sites. Furthermore, the (7x7)-PtTe2-x sample features outstanding catalytic stability even compared to the state-of-the-art Pt/C catalyst. Theoretical calculations reveal that the interactions between various undercoordinated Pt sites due to proximity effect can provide superior undercoordinated Pt sites for hydrogen adsorption and water dissociation. This work will enrich the understanding of the relationship between defect structures and electrocatalytic activities and provide a promising route to develop efficient Pt-based TMD electrocatalysts

CO-stabilisation mechanisms of nanoparticles and surfactants in Pickering emulsions produced by membrane emulsification

Two different membrane emulsification methods were used to study mechanisms for co-stabilisation of emulsions, by either electrostatic or steric stabilised nanoparticles with anionic, cationic or non-ionic surfactants. The experimental results demonstrated the existence of two distinct co-stabilisation mechanisms that arise from interactions of the nanoparticles and surfactant molecules. When significant interaction is not involved, independent competitive adsorption of nanoparticles and surfactant molecules occurs spontaneously to stabilise droplets in formation. The adsorption/desorption equilibrium between surfactant molecules determines the longevity of the droplet stability. When the surfactant molecule reacts with the nanoparticle surface, the resultant surface modification appears to generate faster wetting kinetics for nanoparticles at the oil/water interface and yields enhanced stabilisation. The paper discusses the implications of controlling these interactions for emulsion production membrane systems

Detachment Activated CyPA/CD147 Induces Cancer Stem Cell Potential in Non-stem Breast Cancer Cells

This work is licensed under a Creative Commons Attribution 4.0 International License.Background: Cancer stem cells (CSCs), responsible for cancer metastasis and recurrence, are generated from non-CSCs after chemo-radiation therapy. This study investigated the induction of CSC potential in non-stem breast cancer cells and the underlying molecular mechanisms in detachment culture. Methods: Bulk breast cancer cells, or sorted non-CSCs and CSCs were cultured under an attached or detached condition to assess CSC numbers, ability to form tumor spheres, expression of stemness markers, and chemoresistance. Lentivirus carrying CD147 shRNA or cDNA was used to manipulate CD147 expression, while CD147 ligand recombinant cyclophilin A (CyPA) or its inhibitor was used to activate or inhibit CD147 signaling. Results: Detachment promoted anoikis resistance, chemoresistance, sphere formation, self-renewal, and expression of stemness markers in breast cancer cells. Detachment increased functional ALDH+ or CD44highCD24–/low CSCs, and induced CSC potential in ALDH– or CD44lowCD24high non-CSCs. Upon detachment, both CD147 expression and CyPA secretion were enhanced, and CyPA-CD147 activation mediated detachment induced CSC potential in non-CSCs via STAT3 signaling. Clinically, CD147 and pSTAT3 were highly co-expressed and correlated with poor overall survival and tumor recurrence in breast cancer patients. Conclusion: This study demonstrates that detachment induces the generation of CSCs from non-stem breast cancer cells via CyPA-CD147 signaling, indicating that targeting CD147 may serve as a potential novel therapeutic strategy for lethal metastatic breast cancer by eliminating induced CSCs.National Basic Research Program (#2015CB553700)National Science and Technology Major Project (#2015ZX09501-009)National Natural Science Foundation of China (#31571469 and #81872349

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte