Confining MoS2 nanocrystals in MOF-derived carbon for high performance lithium and potassium storage

Developing an efficient synthesis protocol to simultaneously control 2D nanomaterials’ size and dispersion is the pivot to optimize their electrochemical performance. Herein, we report the synthesis of uniform MoS2 nanocrystals well-anchored into the void space of porous carbon (donated as MoS2⊂C hybrids) by a simple confined reaction in metal–organic framework (MOF) during carbonization process. The strong confinement effect refrain MoS2 growth and aggregation, generating abundant active centers and edges, which contribute fast lithium/potassium reaction kinetics. In addition to the hybridization with the derived carbon, the MoS2⊂C hybrids exhibit rapid Li+ transfer rate (∼10−9 cm2 s−1) and greatly improved electronic conductivity. Consequently, the MoS2⊂C hybrids show ultrafast rate performances and satisfactory cycling stabilities as anode materials for both lithium and potassium ion batteries. This work demonstrates a universal tactic to achieve high dispersive 2D nanomaterials with tailorable particle size. © 2020 Institute of Process Engineering, Chinese Academy of SciencesNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21975074, 91534202, 91834301]; Basic Research Program of Shanghai [17JC1402300]; Shanghai Scientific and Technological Innovation Project [18JC1410500]; National Program for Support of TopNotch Young Professionals; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [222201718002

Integrating Strategies of Herbal Metabolomics, Network Pharmacology, and Experiment Validation to Investigate Frankincense Processing Effects

In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and preparation high-performance liquid chromatography (PHPLC) techniques were used for major compounds isolation and minor compounds concentration. Processed frankincense was subjected to two stepwise solvent systems, namely, n-hexane:ethanol:water (6:5:1) and n-hexane:methyl-acetate:acetonitrile:water (4:4:3:4), to yield 12 fractions, and 18 compounds were further separated. Second, a comprehensive metabolomic analysis conducted by ultrahigh-performance liquid-chromatography/electrospray-ionization mass spectrometry (UHPLC-Qtof-MS) coupled with multivariate statistics was performed to fully characterize the chemical components and discover the potential biomarkers between frankincense and processed frankincense. In total, 81 metabolites, including the 18 separated compounds, were selected as potential biomarkers between frankincense and processed frankincense among 153 detected compounds for their VIP values of greater than one. The tirucallane-type compounds and components with 9,11-dehydro structures clearly occurred at high levels in the processed frankincense, while lupine-type compounds and those with 11-keto structures were significantly higher in frankincense. Then, a network pharmacology model was constructed to decipher the potential mechanisms of processing. Intestinal absorption properties prediction indicated the possibility of processing-related absorption enhancement. A systematic analysis of the constructed networks showed that the C-T network was constructed with 18 potential biomarkers and 69 targets. TNF and IL-1β were among the top-ranked and were linked by 8 and 7 pathways, which were mainly involved in inflammation. The arachidonic acid metabolism pathway exhibited the highest number of target connections. Finally, the prediction was validated experimentally by an intestinal permeability and efficacy assay. The experiments provided convincing evidence that processed frankincense harbored stronger inhibition effects toward TNF-α-, IL-1β- and arachidonic acid-induced platelet aggregation. The processing procedure leads to changes of the chemical metabolites, which triggers the enhancement of absorption and cure efficiency. The global change of the metabolites, absorption and pharmacological effects of processing were depicted in a systematic manner

Differential features of early childhood motor skill development and working memory processing: evidence from fNIRS

ObjectiveThe study investigated the differential characteristics associated with motor skill development and working memory processing during early childhood, thereby providing insights for understanding motor learning and cognitive development in young children.MethodsIn total, 101 preschool children (age: 4–6 years) were recruited for this study. The motor skill development level and the working memory capacity of the children were assessed using the MOBAK Motor Development Assessment Scale and a block task paradigm, respectively. Functional near-infrared spectroscopy brain imaging technology was used to monitor hemodynamic signals in the prefrontal cortex (PFC) of the children while they completed different memory tasks. MATLAB software and the Homer2 plugin were used to calculate the oxygenated hemoglobin (Oxy-Hb) concentration in relevant brain regions during the tasks.Results(1) The low motor skill group exhibited significantly lower accuracy during the three-memory load condition than during the two-memory load condition. Under both two-memory and three-memory load conditions, the high motor skill group exhibited significantly higher accuracy than the low motor skill group. (2) Significant differences in the Oxy-Hb concentration were observed in the left dorsolateral PFC (L-DLPFC), and right and left triangular part of the Broca’s area (R-PTBA and L-PTBA, respectively) between the two memory difficulty levels for the high motor skill group. The Oxy-Hb concentration was significantly higher during the three-memory load condition than during the two-memory load condition. Under the two-memory load condition, the high motor skill group exhibited significantly higher Oxy-Hb concentration in the L-DLPFC and L-PTBA regions than in the low motor skill group. Under the three-memory load condition, the high motor skill group exhibited significantly higher Oxy-Hb concentration in the L-DLPFC, R-PTBA, and L-PTBA regions than the low motor skill group.ConclusionA close association was observed between the motor skill levels and working memory in young children, with higher motor skill levels being associated with more pronounced brain activation patterns during working memory tasks

Achieving blood pressure control targets in hypertensive patients of rural China - A pilot randomized trial

Background: This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China. Methods: A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to \u3c 150 mmHg; moderately intensive: 130 to \u3c 140 mmHg; and intensive: \u3c 130 mmHg. The patients were followed for 6 months. Discussion: The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population\u27s characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets (\u3c 150, \u3c 140, and \u3c 130 mmHg) in a sample of rural, Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2 mmHg, 131.1 mmHg, and 124.2 mmHg, respectively, in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 h after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intensive group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events, including dry cough, palpitations, and arthralgia, were low and showed no significant differences between the three groups. This trial provided real-world experience and laid the foundation for a future, large-scale, BP target study. Trial registration: Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016

Exploiting an Allosteric Binding Site of PRMT3 Yields Potent and Selective Inhibitors

Protein arginine methyltransferases (PRMTs) play an important role in diverse biological processes. Among the nine known human PRMTs, PRMT3 has been implicated in ribosomal biosynthesis via asymmetric dimethylation of the 40S ribosomal protein S2 and in cancer via interaction with the DAL-1 tumor suppressor protein. However, few selective inhibitors of PRMTs have been discovered. We recently disclosed the first selective PRMT3 inhibitor, which occupies a novel allosteric binding site and is noncompetitive with both the peptide substrate and cofactor. Here we report comprehensive structure-activity relationship studies of this series, which resulted in the discovery of multiple PRMT3 inhibitors with submicromolar potencies. An X-ray crystal structure of compound 14u in complex with PRMT3 confirmed that this inhibitor occupied the same allosteric binding site as our initial lead compound. These studies provide the first experimental evidence that potent and selective inhibitors can be created by exploiting the allosteric binding site of PRMT3

Structural Studies of a Four-MBT Repeat Protein MBTD1

The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats.We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a "cavity insertion recognition mode" to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation.The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

S100A14 Stimulates Cell Proliferation and Induces Cell Apoptosis at Different Concentrations via Receptor for Advanced Glycation End Products (RAGE)

S100A14 is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effects on different types of cells. However, exact extracellular roles of S100A14 have not been clarified yet. Here we investigated the effects of S100A14 on esophageal squamous cell carcinoma (ESCC) cell lines. Results demonstrated that low doses of extracellular S100A14 stimulate cell proliferation and promote survival in KYSE180 cells through activating ERK1/2 MAPK and NF-κB signaling pathways. Immunoprecipitation assay showed that S100A14 binds to receptor for advanced glycation end products (RAGE) in KYSE180 cells. Inhibition of RAGE signaling by different approaches including siRNA for RAGE, overexpression of a dominant-negative RAGE construct or a RAGE antagonist peptide (AmphP) significantly blocked S100A14-induced effects, suggesting that S100A14 acts via RAGE ligation. Furthermore, mutation of the N-EF hand of S100A14 (E39A, E45A) virtually reduced 10 µg/ml S100A14-induced cell proliferation and ERK1/2 activation. However, high dose (80 µg/ml) of S100A14 causes apoptosis via the mitochondrial pathway with activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase. High dose S100A14 induces cell apoptosis is partially in a RAGE-dependent manner. This is the first study to demonstrate that S100A14 binds to RAGE and stimulates RAGE-dependent signaling cascades, promoting cell proliferation or triggering cell apoptosis at different doses