Paeonol Attenuated Inflammatory Response of Endothelial Cells via Stimulating Monocytes-Derived Exosomal MicroRNA-223

Introduction: Paeonol, an active compound isolated from the radix of Cortex Moutan, has been shown to have anti-atherosclerosis effects by regulating blood cells’ function and protecting vascular cells injury. Besides, emerging evidences has proven that exosomes might play a pivotal role in intercellular communication by transmiting proteins and microRNAs from cell to cell. However, the relationship between monocytes-derived exosomal microRNA-223 and vascular inflammation injury along with paeonol’ effects are still not clear.Objective: Our study aimed to explain whether paeonol’s protective effect on inflammatory response is related to the regulation of exosomal microRNA-223 in the VECs.Methods: ApoE−/− mice were fed with high fat diet to replicate the AS model. HE staining and immunohistochemistry was used to detect inflammatory response of aorta. The expression of IL-1β and IL-6 were detected by ELISA. Western blot was used to detect the expression of STAT3, pSTAT3, ICAM-1 and VCAM-1. qRT-PCR was used to detect miR-223 expression. Exosomes were extracted from THP-1 cells by differential centrifugation and observed by transmission electron microscope. Observation of exosomes uptake into HUVECs was realized by laser microscopy. miR-223 target gene was detected by double luciferase gene report test.Results:In vivo experiments confirmed that paeonol restricted atherosclerosis development and increased miR-223 expression, inhibited STAT3 pathway in ApoE−/− mice. In vitro, miR-223 showed robust presence in THP-1 cells and undetectable in HUVECs. And we had observed that miR-223 could be internalized from THP-1 cells into HUVECs taking exosomes as a carrier. Paeonol obviously increased miR-223 expression in co-cultured HUVECs and exosomes in concentration dependent manner, compared to LPS group. In addition, paeonol relieved inflammatory secretion, adhesion and STAT3 expression in HUVECs, which could be inverted after miR-223 inhibitor transfection into THP-1 cells.Conclusion: Paeonol could increase the expression of miR-223 in THP-1 derived exosomes and in HUVECs after uptake of exosomes, whereas decrease the expression of STAT3, p-STAT3 in HUVECs. Ultimately paeonol decreased the expression of IL-1β, IL-6, ICAM-1, VCAM-1 in HUVECs and alleviated adhesion of THP-1 cells to HUVECs

Mesoporous High‐Surface‐Area Copper–Tin Mixed‐Oxide Nanorods: Remarkable for Carbon Monoxide Oxidation

Mesoporous, high‐surface‐area Cu–Sn mixed‐oxide nanorods were fabricated for the first time by nanocasting with the use of mesoporous KIT‐6 silica as the hard template. The Cu–Sn nanorods are significantly more active than 1 % Pd/SnO2 for the oxidation of CO and possesses long‐term durability and potent water resistance; they thus have the potential to replace noble metal catalysts for emission‐control processes.In rod we trust: Mesoporous, high‐surface‐area Cu–Sn nanorods are successfully fabricated for the first time by nanocasting with the use of KIT‐6 silica as the hard template; these nanomaterials are significantly more active than 1 % Pd/SnO2 for the oxidation of CO, and furthermore, they have the potential to replace noble metal catalysts for emission control.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/1/cctc201600221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/2/cctc201600221-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/3/cctc201600221_am.pd

Portable gas chromatography–mass spectrometry method for the in‑feld screening of organic pollutants in soil and water at pollution incidents

Environmental pollution incidents generate an emergency response from regulatory agencies to ensure that the impact on the environment is minimised. Knowing what pollutants are present provides important intelligence to assist in determining how to respond to the incident. However, responders are limited in their in-feld capabilities to identify the pollutants present. This research has developed an in-feld, qualitative analytical approach to detect and identify organic pollutants that are commonly detected by regulatory environmental laboratories. A rapid, in-feld extraction method was used for water and soil matrices. A coiled microextraction (CME) device was utilised for the introduction of the extracted samples into a portable gas chromatography–mass spectrometry (GC–MS) for analysis. The total combined extraction and analysis time was approximately 6.5 min per sample. Results demonstrated that the in-feld extraction and analysis methods can screen for ffty-nine target organic contaminants, including polyaromatic hydrocarbons, monoaromatic hydrocarbons, phenols, phthalates, organophosphorus pesticides, and organochlorine pesticides. The method was also capable of tentatively identifying unknown compounds using library searches, signifcantly expanding the scope of the methods for the provision of intelligence at pollution incidents of an unknown nature, although a laboratory-based method was able to provide more information due to the higher sensitivity achievable. The methods were evaluated using authentic casework samples and were found to be ft-for-purpose for providing rapid in-feld intelligence at pollution incidents. The fact that the in-feld methods target the same compounds as the laboratory-based methods provides the added beneft that the in-feld results can assist in sample triaging upon submission to the laboratory for quantitation and confrmatory analysis

Influence of long-term fertilization on soil aggregates stability and organic carbon occurrence characteristics in karst yellow soil of Southwest China

Current research has long focused on soil organic carbon and soil aggregates stability. However, the effects of different long-term fertilization on the composition of yellow soil aggregates and the characteristics of the occurrence of organic carbon in the karst region of Southwest China are still unclear. Based on a 25-year long-term located experiment on yellow soil, soil samples from the 0–20 cm soil layer were collected and treated with different fertilizers (CK: unfertilized control; NPK: chemical fertilizer; 1/4 M + 3/4 NP: 25% chemical fertilizer replaced by 25% organic fertilizer; 1/2 M + 1/2 NP: 50% chemical fertilizer replaced by organic fertilizer; and M: organic fertilizer). In water-stable aggregates, soil aggregates stability, total organic carbon (TOC), easily oxidized organic carbon (EOC), carbon preservation capacity (CPC), and carbon pool management index (CPMI) were analyzed. The findings demonstrated that the order of the average weight diameter (MWD), geometric mean diameter (GWD), and macro-aggregate content (R0.25) of stable water aggregates was M > CK > 1/2M +1/2NP > 1/4M +3/4NP> NPK. The MWD, GWD, and R0.25 of NPK treatment significantly decreased by 32.6%, 43.2%, and 7.0 percentage points, respectively, compared to CK treatment. The order of TOC and EOC content in aggregates of different particle sizes was M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, and it increased as the rate of organic fertilizer increased. In macro-aggregates and bulk soil, the CPC of TOC (TOPC) and EOC (EOPC), as well as CPMI, were arranged as M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, but the opposite was true for micro-aggregates. In bulk soil treated with organic fertilizer, the TOPC, EOPC, and CPMI significantly increased by 27.4%–53.8%, 29.7%–78.1%, 29.7–82.2 percentage points, respectively, compared to NPK treatment. Redundancy analysis and stepwise regression analysis show that TOC was the main physical and chemical factor affecting the aggregates stability, and the TOPC in micro-aggregates has the most direct impact. In conclusion, the primary cause of the decrease in SOC caused by the long-term application of chemical fertilizer was the loss of organic carbon in macro-aggregates. An essential method to increase soil nutrient supply and improve yellow soil productivity was to apply an organic fertilizer to increase aggregates stability, storage and activity of SOC in macro-aggregates

On the characteristics of the wake of a wind turbine undergoing large motions caused by a floating structure: an insight based on experiments and multi-fidelity simulations from the OC6 Phase III Project

This study reports the results of the second round of analyses of the OC6 project Phase III. While the first round investigated rotor aerodynamic loading, here focus is given to the wake behavior of a floating wind turbine under large motion. Wind tunnel experimental data from the UNsteady Aerodynamics for FLOating Wind (UNAFLOW) project are compared with the results of simulations provided by participants with methods and codes of different levels of fidelity. The effect of platform motion both on the near and the far wake is investigated. More specifically, the behavior of tip vortices in the near wake is evaluated through multiple metrics, such as streamwise position, core radius, convection velocity, and circulation. Additionally, the onset of velocity oscillations in the far wake is analyzed because this can have a negative effect on stability and loading of downstream rotors. Results in the near wake for unsteady cases confirm that simulations and experiments tend to diverge from the expected linearized quasi-steady behavior when the rotor reduced frequency increases over 0.5. Additionally, differences across the simulations become significant, suggesting that further efforts are required to tune the currently available methodologies in order to correctly evaluate the aerodynamic response of a floating wind turbine in unsteady conditions. Regarding the far wake, it is seen that, in some conditions, numerical methods over-predict the impact of platform motion on the velocity fluctuations. Moreover, results suggest that, different from original expectations about a faster wake recovery in a floating wind turbine, the effect of platform motion on the far wake seems to be limited or even oriented to the generation of a wake less prone to dissipation.</p

Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

BACKGROUND: The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). METHODOLOGY/PRINCIPAL FINDINGS: We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. CONCLUSIONS: These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence

Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features

BackgroundCerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP).MethodsWith a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuro-inflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used.Findings369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (&gt;1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%.InterpretationThe nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism