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Background: Multiple studies have demonstrated that the gut microbiome is closely related to the onset of Alzheimer's disease, but the causal relationship between the gut microbiome and AD, as well as potential mediating factors, have not been fully explored. Objective: Our aim is to validate the causal relationship between the gut microbiome and the onset of AD and determine the key mechanism by which the gut microbiome mediates AD through blood metabolites using Mendelian randomization (MR) analysis methods. Methods: We first conducted bidirectional and mediating MR analyses using gut microbiota, blood amino acid metabolites, and AD-related single nucleotide polymorphisms as research data. In the analysis process, the inverse variance-weighted average method was mainly used as the primary method, with other methods serving as supplementary evidence. Results: Ultimately, we found that six types of gut bacteria and two blood amino acid metabolites have a causal effect on AD. Subsequent mediation analysis proved that decreased glutamine concentration mediates the negative causal effect of Holdemanella bacteria on AD (mediation ratio of 14.5%), and increased serum alanine concentration mediates the positive causal effect of Parabacteroide bacteria on AD (mediation ratio of 9.4%). Conclusions: Our study demonstrates the causality of Holdemanella and Parabacteroides bacteria in the onset of AD and suggests that the reduced glutamine and increased alanine serums concentration may be key nodes in mediating this effect. [ABSTRACT FROM AUTHOR]

The MLE of the ATE in the logit model for binary outcomes may have a significant second-order bias if the event has a low probability, which is the case we focus on in this article. We derive the second-order bias of the logit ATE estimator, and we propose a bias-corrected estimator of the ATE. We also propose a variation on the logit model with parameters that are elasticities. Finally, we propose a computational trick that avoids numerical instability in the case of estimation for rare events. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between total sleep duration variability and stroke in the middle-aged and elderly population in China. Methods: Data were collected from the 2011, 2013, 2015, and 2018 surveys of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3485 participants, who had not experienced a stroke until 2015 and completed the follow-up in 2018, were enrolled to analyze the relationship between total sleep duration variability and new stroke. Total sleep duration was calculated by summing self-reported nocturnal sleep duration and daytime napping. The variability was determined by calculating the standard deviation (SD) of total sleep duration across the first three waves. A binary logistic regression model was utilized to analyze this association. Results: Of the 3485 participants, 183 (5.25%) sustained a stroke event. A dose-response relationship was observed, indicating an increased stroke risk of 0.2 per unit (hours) increase in total sleep duration variability [OR (95% CI): 1.20 (1.01–1.42)]. Upon stratification by sex groups, this increased risk was significant only in men [OR (95% CI): 1.44 (1.12–1.83)]. Conclusion: Increased total sleep duration variability was associated with an increased risk of stroke in the middle-aged and elderly, independent of factors such as age, nocturnal sleep duration, napping habits, region of residence, hypertension, diabetes mellitus, dyslipidemia, BMI, smoking, drinking habits, and marital status. However, a more notable correlation was observed in males. [ABSTRACT FROM AUTHOR]

Temperature compensation is the main measure to solve the problem that the detection accuracy of non-dispersive infrared CO2 gas sensor is affected by temperature. As the measurement accuracy of the non-dispersive infrared CO2 gas sensor is easily affected by the ambient temperature, this article analyzes the reasons why the sensor is affected by temperature, and proposes a temperature compensation method that integrates the Whale Algorithm (WOA) and BP neural network. The whale algorithm is used to optimize the weights and thresholds of the BP neural network to build a temperature compensation model for the non-dispersive infrared CO2 gas sensor and compare the superiority with the traditional BP neural network model and particle swarm optimization (PSO) BP neural network model. The experimental results show that the temperature compensation model error of WOA-BP algorithm is lower than 30 ppm, and the average absolute error percentage is 3.86%, which is far better than BP neural network and PSO-BP neural network, and effectively reduces the influence of temperature on the accuracy of the sensor. [ABSTRACT FROM AUTHOR]

Massively parallel sequencing (MPS) has emerged as a promising technology for targeting multiple genetic loci simultaneously in forensic genetics. Here, a novel 193-plex panel was designed to target 28 A-STRs, 41 Y-STRs, 21 X-STRs, 3 sex-identified loci, and 100 A-SNPs by employing a single-end 400 bp sequencing strategy on the MGISEQ-2000™ platform. In the present study, a series of validations and sequencing of 1642 population samples were performed to evaluate the overall performance of the MPS-based panel and its practicality in forensic application according to the SWGDAM guidelines. In general, the 193-plex markers in our panel showed good performance in terms of species specificity, stability, and repeatability. Compared to commercial kits, this panel achieved 100% concordance for standard gDNA and 99.87% concordance for 14,560 population genotypes. Moreover, this panel detected 100% of the loci from 0.5 ng of DNA template and all unique alleles at a 1:4 DNA mixture ratio (0.2 ng minor contributor), and the applicability of the proposed approach for tracing and degrading DNA was further supported by case samples. In addition, several forensic parameters of STRs and SNPs were calculated in a population study. High CPE and CPD values greater than 0.9999999 were clearly demonstrated and these results could be useful references for the application of this panel in individual identification and paternity testing. Overall, this 193-plex MPS panel has been shown to be a reliable, repeatable, robust, inexpensive, and powerful tool sufficient for forensic practice. [ABSTRACT FROM AUTHOR]

Data centers are usually characterized by high energy loads, which raises increasing sustainability concerns in both academic and daily usage. To mitigate the uncertainty and high volatility of distributed wind energy generation, this paper proposes a hybrid energy storage allocation strategy by means of the Empirical Mode Decomposition (EMD) technique and the two-stage robust method. First, this paper conducts the evolution analyses for the over- and under-evaluated uncertainty of wind power fluctuation under different time scales. Second, we employ the EMD technique to configure a high-frequency flywheel energy storage device, realizing the wind power transformation from large fluctuations to small fluctuations and the convergence of the wind power fluctuation curves in minute- and hour levels. Finally, based on the hour-level wind energy stable power curves, we carry out two-stage robust planning for the equipment capacity of low-frequency cold storage tanks and lithium bromide chillers. The case study on a data center microgrid in northeastern China confirms the effectiveness of our proposed strategy. [ABSTRACT FROM AUTHOR]

Aiming at the problem of wind curtailment caused by the lack of system flexibility, an optimal scheduling strategy for improving the flexibility of the electricity-gas- heat interconnection system by the coordinated operation of the gas network management and storage characteristics and the heat storage characteristics of the heat network is proposed. Firstly, the influence of gas network storage and heat network storage on improving flexibility is analyzed respectively. Then, an electricity-gas-heat interconnected system scheduling model considering the dynamic characteristics of gas network management and t the delay characteristics of heat storage in heat network, which greatly improves the imbalance between supply and demand of flexibility in space and time brought by the anti-peak regulation characteristics of wind power to the system. Finally, the IEEE-24 nodes power system, Belgium's 20-node natural gas network and 6- node thermal network are used, for example, analysis. The results show that the proposed scheduling scheme improves the flexibility of the system while its operating cost and wind curtailment cost are the lowest, which promotes the consumption of wind power. [ABSTRACT FROM AUTHOR]

Black polyimides (BPIs) have attracted increasing attention owing to their growing demand in optoelectronics. However, commonly used black polyimides doped with black fillers suffer from poor mechanical and electrical properties. To address these issues, a new diamine (2,5-bis(4′-amino-[1,1′-biphenyl]-4-yl)-3,4-bis(4-fluorophenyl)cyclopenta-2,4-dien-1-one, TPCPFPDA) bearing a tetraphenylcyclopentadienone (TPCP) moiety bonded with benzene and fluorine units was synthesized. The diamine was reacted with 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) to yield a soluble intrinsic black polyimide (TPCPFPPI). Bonding fluorine (auxochrome group) and benzene units to TPCP can increase the conjugation of π-electrons systems and facilitate the movement of electron throughout the big π bond, respectively. Owing to the structural features, the synthesized TPCPFPPI exhibited complete visible-light absorption with high blackness and opacity. Its cutoff wavelength (λcut) and CIE (Commission Internationale de I' Eclairage) parameter L* were 684 nm and 1.33, respectively. Moreover, TPCPFPPI displayed exceptional electrical, mechanical, and thermal properties as well as excellent solubility. A detailed theoretical calculation was conducted to gain better insight into the electronic properties of the TPCPFPPI. Results showed that the blackness of TPCPFPPI was chiefly attributed to the electron transition from highest occupied molecular orbital (HOMO) to lowest unoccupied molecular orbital (LUMO) in the diamines, where the charges primarily migrated from the aryl groups in the 2- and 5-positions to the cyclopentadienone center. The as-obtained intrinsic BPI (TPCPFPPI), exhibiting both high solubility and outstanding overall properties, has important applications in photo-electronics. [ABSTRACT FROM AUTHOR]

There are various shaped sections of slotted-in steel plates and timber grooves among the bolted timber joints with slotted-in steel plates to satisfy the design and assembly criteria in practical engineering. The different shapes affect the performance but have not been widely researched. To visualize the effect of shaped sections on the joints and provide some experience for targeting improving the ductility, we performed monotonic loading tests parallel to the grain on 16 sets of the proposed end U-shaped carbon fiber reinforced plastics (CFRP)–bolted timber joints with slotted-in corrugated steel plates. The effects of the wavelength, wave height, wave angle, timber thickness, number of CFRP layers, and interaction between the parameters were mainly considered. The results showed that the joints were susceptible to failure as a result of a number of manifestations, including shear damage, pressure damage, opening-mode cleavage in the grain direction (TL cleavage), CFRP cleavage, etc. Similarly, the joints had multiple combinations of yielding deformation modes of bolts, which included IS , IS & IIIS , IIIS , IIIS & IV, and V. The load-displacement curve showed that the joints mainly undergo the elastic stage, the fracture failure transition stage, and the fracture failure stage without an obvious yield stage. According to the experimental results, an orthogonal parametric analysis of the mechanical properties was conducted and the degree and pattern of each parameter were obtained. Among them, each parameter affected the elastic stiffness relatively less; wave height and wave angle had relatively significant influences on the ultimate strength and ductility, and the ultimate strength fluctuated with the increasing wave height, but negatively correlated with wave angle, while the ductility was negatively correlated with both. Additionally, a strength formula was derived by theoretical analysis, and a good agreement was indicated by the average ratio of 1.03 between the theoretical and experimental results. This study contributes to the understanding of the effect of shaped slotted-in steel plates on the mechanical behavior of bolted timber joints with slotted-in steel plates and provides some theoretical and experience basis for the reinforcement. However, this study is mainly focused on spruce and slotted-in corrugated steel plates, which still need to be adequately investigated for other tree species and cross-sectional forms, especially the fracture characteristics. In addition, the group effect of bolted timber joints is more significant, which needs to be specifically studied for the design in engineering applications. [ABSTRACT FROM AUTHOR]

With growing attention to the protection of circuit design, the demand of black polyimide (BPI) for flexible printed circuit board (FPCB) is increasing. However, the existing BPIs suffer from problems of poor mechanical and electrical properties, low solubility and masking capacity. To address these issues, a diamine monomer (TPCPODA) containing tetraphenylcyclopentadienone (TPCP) connected with phenyl ether unit was designed and prepared, which was subsequently reacted with 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) to prepare a soluble intrinsic BPI (TPCPOPI). TPCP grafted with phenyl ether acts as chromophores that shift the absorption scope of PI to the long wave direction. The resulted TPCPOPI shows a cut-off wavelength (λcut) high to 673 nm. Theoretical calculations suggest that the visible absorption of TPCPOPI is mostly resulted from the electrons transitions of HOMO to LUMO within diamines moiety, in which the charges chiefly migrate from the aryl units at 2, 5-position to cyclopentadienone. Moreover, TPCPOPI shows outstanding electrical, mechanical and thermal properties and excellent solubility. Further investigation shows that the TPCPOPI-based two-layer flexible copper clad laminates (2L-FCCLs) has high peeling strength due to the incorporation of ketone and ether units. This work offers a prospective solution for the property improvement of BPIs for FPCBs. [ABSTRACT FROM AUTHOR]

Black polyimides (BPIs) have gained increasing attention because of their growing demands in optoelectronic areas. However, the commonly used BPI containing carbon black suffers from the decreases of mechanical and electrical performances. In this work, a soluble intrinsic BPI (TPCPDFPPI) was prepared by the reaction of 4,4′‐(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and a new diamine (TPCPDFPDA) bearing tetraphenylcyclopentadienone (TPCP) connected with benzene and fluorene units. TPCP grafted with benzene and fluorene units acted as a chromophore that shifted the absorption range of PI toward the long‐wave direction. The resulting TPCPDFPPI possessed whole visible‐light absorption characteristic and therefore exhibited high blackness and opacity. Additionally, TPCPDFPPI displayed superior solubility, mechanical and electrical performance. Theoretical calculations exhibited that the visible‐light absorption responsible for the blackness of TPCPDFPPI was chiefly ascribed to the HOMO to LUMO electron transition in the diamines, where the electrons were primarily migrated from the 2,5‐position aryl groups to the cyclopentadienone. This work offers a promising strategy for improving the overall properties of BPIs for photo‐electronic areas. [ABSTRACT FROM AUTHOR]

Depression is a prevalent mental illness that imposes a substantial public health burden. However, the diverse clinical phenotypes observed in patients make it difficult to realize precise diagnosis. Recently, accumulating preclinical and clinical evidence has suggested that inflammation is involved in the pathophysiology of depression. Herein, a molecular imaging–based strategy was proposed as a means to diagnose depression precisely by specifically visualizing the inflammation status associated with depression. Inflammation-targeting MRI nanoprobes were constructed by attaching an intercellular cell adhesion molecule-1 (ICAM-1)-targeting peptide to biocompatible Fe3O4 nanoparticles. Systematic studies demonstrated that the nanoprobes could specifically target inflamed vascular endothelial cells and visualize the spatial distribution of inflammation in the depressed brain in vivo through susceptibility-weighted imaging (SWI), which was further confirmed by histological analysis. Additionally, these inflammatory brain regions identified by nanoprobe-based imaging are consistent with the focal regions closely associated with the symptoms of depression as reported in previous behavioral studies. Overall, this is the first study to directly visualize the distribution of inflammation in the depressed brain in vivo through a molecular imaging strategy, which may not only facilitate insight into the biological mechanism underlying depression but also provide a potential target within the depressed brain for the further development of anti-inflammatory therapies. A molecular imaging-based strategy was proposed for precise diagnosing the depression through specifically visualizing the inflammation status associated with depressed brain. The inflammation-targeting MRI nanoprobe that can specifically target the inflamed vascular endothelial cells was constructed through attaching the ICAM-1 targeting peptides on biocompatible Fe3O4 nanoparticle. Through nanoprobe-based SWI, the spatial distribution of inflammation in depressed brain can be mapped in vivo. This strategy not only facilitate insight into the biological mechanism underlying depression, but also provide a target within the depressed brain for the further development of anti-inflammatory therapies. [ABSTRACT FROM AUTHOR]

Background: Silent Information Regulator 2 (SIRT2) protein inhibition has been shown to play a neuroprotective role in acute ischemic stroke (AIS) in mice. However, its role in AIS patients has not been fully understood. In this study, we aimed to analyze SIRT2 protein expression in serum exosomes of AIS and non-AIS patients, and evaluate its potential role in diagnosis and prognosis of AIS. Methods: Serum exosomes from 75 non-AIS subjects and 75 AIS patients were isolated. The SIRT2 protein levels in exosomes were analyzed using enzyme linked immunosorbent assay (ELISA). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of the disease. The modified Rankin Scale (mRS) was employed to assess the functional outcomes of the patients at 3-months following stroke onset. Results: The SIRT2 protein concentration of serum exosomes were higher in AIS patients than non-AIS patients (p < 0.001). Furthermore, the receiver operative characteristic curve (ROC) demonstrated that higher serum exosome SIRT2 could differentiate AIS patients from non-AIS patients with a sensitivity of 81.3% and a specificity of 75.3%. The area under the curve was 0.838 (95% CI: 0.775, 0.902). Additionally, higher SIRT2 concentration of serum exosomes were associated with NIHSS ≥ 4 (p < 0.001) and mRS ≥ 3 (p = 0.025) in AIS patients. The ROC analysis showed SIRT2 could discriminate stroke with NIHSS ≥ 4 from mild stroke (NIHSS < 4) with a sensitivity of 75.0% and a specificity of 69.6%. The area under the curve was 0.771 (95% CI: 0.661,0.881). Similarly, the test showed SIRT2 could differentiate between AIS patients with mRS ≥ 3 from those with mRS < 3 with a sensitivity of 78.3% and a specificity of 51.9%. The area under the curve was 0.663 (95% CI: 0.531,0.796). The logistic regression analysis revealed that SIRT2 concentration in serum exosomes can independently predict the diagnosis of AIS (odd ratio = 1.394, 95%CI 1.231–1.577, p < 0.001) and higher NIHSS scores (≥ 4) (odd ratio = 1.258, 95%CI 1.084–1.460, p = 0.002). However, it could not independently predict the prognosis of AIS (odd ratio = 1.065, 95%CI 0.983–1.154, p = 0.125). Conclusion: The elevation of SIRT2 in serum exosomes may be a valuable biomarker of AIS, which may be a potential diagnostic tool to facilitate decision making for AIS patients. [ABSTRACT FROM AUTHOR]

This study focuses on a small agricultural diesel engine fueled with B20 (20% biodiesel and 80% diesel by volume) blend fuel in a plateau area. The combustion chamber's structural parameters and fuel injection angle were taken as variables at peak torque conditions. First, a full factorial design was used for experimental design. Second, the back-propagation (BP) neural network was employed to predict the indicated thermal efficiency and the indicated specific NOx emission. Third, the non-dominated sorting genetic algorithm-II (NSGA-II) was utilized to optimize the indicated thermal efficiency and the indicated specific NOx emission. Finally, the technique for order of preference by similarity to ideal solution (TOPSIS) method was applied to obtain optimal solutions, and a three-dimensional numerical simulation was conducted to verify the optimization results. The optimization results indicate that the shape characteristics of the combustion chamber have a certain influence on the engine's performance. The optimized design significantly reduces NOx emissions, by 22.83%, compared to the original engine, whilst maintaining the engine's performance. [ABSTRACT FROM AUTHOR]

In forensics, accurate identification of the origin of body fluids is essential for reconstructing a crime scene or presenting strong evidence in court. Microorganisms have demonstrated great potential in body fluid identification. We developed a multiplex PCR system for forensic salivary identification, which contains five types of bacteria:Streptococcus salivarius, Neisseria subflava, Streptococcus. mutans, Bacteroides thetaiotaomicron, and Bacteroides. uniformis. And the validated studies were carried out following the validation guidelines for DNA analysis methods developed by the Scientific Working Group on DNA Analysis Methods (SWGDAM), which included tests for sensitivity, species specificity, repeatability, stability, and mixed samples, trace samples, case samples, and a population study. Our result depicted that the lowest detection limit of the system was 0.01 ng template DNA. Moreover, the corresponding bacteria can still be detected when the amount of saliva input is low to 0.1 μL for DNA extraction. In addition, the target bacteria were not detected in the DNA of human, seven common animals, and seven bacteria DNA and in nine other body fluid samples (skin, semen, blood, menstrual blood, nasal mucus, sweat, tears, urine, and vaginal secretions). Six common inhibitors such as indigo, EDTA, hemoglobin, calcium ions, alcohol and humic acid were well tolerated by the system. What is more, the salivary identification system recognized the saliva component in all mixed samples and simulated case samples. Among 400 unrelated individuals from the Chinese Han population analyzed by this novel system, the detection rates of N. subflava, S. salivarius, and S. mutans were 97.75%, 70.75%, and 19.75%, respectively, with 100% identification of saliva. In conclusion, the salivary identification system has good sensitivity, specificity, stability, and accuracy, which can be a new effective tool for saliva identification. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID‐19) pandemic posed great impacts on public health. To fight against the pandemic, robust immune responses induced by vaccination are indispensable. Previously, we developed a subunit vaccine adjuvanted by aluminum hydroxide, ZF2001, based on the dimeric tandem‐repeat RBD immunogen, which has been approved for clinical use. This dimeric RBD design was also explored as an mRNA vaccine. Both showed potent immunogenicity. In this study, a DNA vaccine candidate encoding RBD‐dimer was designed. The humoral and cellular immune responses induced by homologous and heterologous prime‐boost approaches with DNA‐RBD‐dimer and ZF2001 were assessed in mice. Protection efficacy was studied by the SARS‐CoV‐2 challenge. We found that the DNA‐RBD‐dimer vaccine was robustly immunogenic. Priming with DNA‐RBD‐dimer followed by ZF2001 boosting induced higher levels of neutralizing antibodies than homologous vaccination with either DNA‐RBD‐dimer or ZF2001, elicited polyfunctional cellular immunity with a TH1‐biased polarization, and efficiently protected mice against SARS‐CoV‐2 infection in the lung. This study demonstrated the robust and protective immune responses induced by the DNA‐RBD‐dimer candidate and provided a heterologous prime‐boost approach with DNA‐RBD‐dimer and ZF2001. [ABSTRACT FROM AUTHOR]

Background: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. Aim: The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. Methods: The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. Results: The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p < 0.001; all-or-none measure 49.2% vs 44.8% patients; absolute difference 3.5%, 95% CI = [2.7%, 4.2%], p < 0.001). Further analysis of individual KPIs showed an absolute increase in six KPIs ranging from 3.4% to 8.9% (p < 0.001 for all comparisons). Compared with 2015–2017, hospital length of stay was shorter (10.95 vs 11.90 days; absolute difference –1.08, 95% CI = [–1.18, –0.99], p < 0.001), and in-hospital mortality was significantly reduced (risk ratio (RR) = 0.88, 95% CI = [0.79, 0.98], p = 0.01) in 2018–2020. Conclusion: The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. Trial registration: ClinicalTrials.gov identifier: NCT02735226. [ABSTRACT FROM AUTHOR]

Purpose: As quality issues become more prominent in supply chain (SC) management, understanding the factors driving SC quality integration (SCIQ) and quality performance has become increasingly important, shifting the focus of quality management to firms in SCs. This study aims to examine the role of SC quality leadership (SCQL) in facilitating SCIQ and its direct and indirect relationship with quality performance. Design/methodology/approach: Data on 400 Chinese manufacturing firms were collected using survey questionnaires. The hypothesised relationships between SCQL, SCIQ and quality performance were tested using structural equation modeling in AMOS 22.0. Findings: Empirical results show that SCQL has a positive and significant effect on quality performance and all three dimensions of SCIQ: supplier quality integration, internal quality integration and customer quality integration. The results also show that SCIQ mediates the relationship between SCQL and quality performance. Practical implications: Executives should develop SCQL to improve SCIQ in their SCs and ultimately improve quality performance. In particular, nurturing SQI can potentially lead to unique capabilities, relative to competitors. They should be aware of their important role in integrating and coordinating between functional units within the firm and between SC members. Originality/value: This study enriches the SCM literature by identifying SCQL as a new and significant antecedent of SCIQ in manufacturing firms. It contributes to the SC leadership literature by conceptualizing both the quality and social responsibility aspects of SC leadership, conceptualizing SCQL at the firm level and positioning SCIQ as a mediator between SCQL and quality performance. [ABSTRACT FROM AUTHOR]

The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays. EdU incorporation, cell cycle analysis, and CCK-8 assay indicated that Lama2 and Samsn1 mediated the inhibitory effect of Brn4 on the proliferation of hippocampal NSCs. Immunofluorescence staining, RT-qPCR, and Western blot suggested that Lama2 and Samsn1 mediated the promoting effect of Brn4 on the differentiation of hippocampal NSCs into neurons. In conclusion, our study demonstrates that Brn4 binds to the promoters of Lama2 and Samsn1, and they partially mediate the regulation of Brn4 on the proliferation inhibition and neuronal differentiation promotion of hippocampal NSCs. [ABSTRACT FROM AUTHOR]

This paper investigated the physical and chemical properties of gasoline direct injection (GDI) engine particulate matter (PM). The physical properties mainly included the particulate aggregate morphology, primary particle size, and internal nanostructure. High-resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM) were used to obtain particle morphology information and to conduct image processing and analysis. The chemical characterization tests included X-ray photoelectron spectroscopy (XPS), energy dispersive scanning (EDS), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). XPS can be used to observe the content of carbon and oxygen components and the surface carbon chemistry status, EDS can be used to obtain the elemental composition of particles, and TGA is used to analyze the oxidative kinetics of particles. Samples were collected from the exhaust emissions of a passenger vehicle compliant with China's VI emission standards under China Light-Duty Vehicle Test Cycle (CLTC) test conditions. The study found that the particle morphology mainly comprised primary particles stacked on top of each other to form agglomerate structures, and the primary particles exhibited a core–shell structure. Analysis showed that carbon and oxygen were the predominant components of the particles, with other metallic elements also present. The XPS observations agreed with the FTIR results, indicating a small amount of oxygen was present on the particle surface and that the carbon components consisted mainly of sp2 hybridized graphite and sp3 hybridized organic carbon. The TGA results indicated high characteristic temperatures and low oxidation activity. [ABSTRACT FROM AUTHOR]

With a bare pin-to-nozzle electrode configuration, an ac-driven non-thermal air plasma jet with a length of several centimeters is generated. Depending on the gas flow rate, the propagation speed of these plasma columns is in the range of 100–350 m/s, which is close to the gas flow velocity. This indicates that the propagation of the plasma jet is determined by the transport of long lifetime species by gas flow instead of the electron-impact excitation and ionization of molecules under a high electric field. In comparison to the N2, O2, and Ar plasma jets, the length of the air plasma jet is much shorter than that of the N2 plasma jet but longer than that of the O2 and Ar plasma jets. A simple kinetic model reveals that the N2 (A3Σ) metastable plays a crucial role in sustaining the length of the N2 and air plasma jets, whose lifetime is strongly dependent on the quenching effect of O2, O, and NO as well as the compensation from the three-body recombination of nitrogen atoms. Based on the flow-dependent mechanism of the plasma jet, a visually uniform air plasma brush with a width of 2.8 cm and a length of 1.6 cm and a visually uniform N2 plasma brush with a width of 4 cm and a length of 4.4 cm have been demonstrated. [ABSTRACT FROM AUTHOR]

Brain oedema is a common pathological phenomenon following many diseases and may lead to severe secondary damage. Astrocytes are the most numerous cells in the brain. Five aquaporins (AQPs) have been found in mature astrocytes, which play crucial roles in water transportation. However, most studies have focused on AQP4 or AQP9 and whether another aquaporin such as AQP5 involved in brain oedema is unclear. Here, we addressed the issue that the expression pattern of AQP5 in rat astrocytes in vitro was altered in the hypotonic condition through some mitogen‐activated protein kinases (MAPK) pathways. Primary astrocytes were randomly divided into the control group and the hypotonic group. Cell viability was evaluated by MTT test. Immunofluorescence, Western blotting and real‐time PCR were used to detect the expression of AQP5. Western blotting was used to detect the variation of MAPK pathway. The present study demonstrated that incubation of astrocytes in the hypotonic medium produced an increase inAQP5 expression, and AQP5 peaked at 6–12 h after hypotension solution exposure. In addition, MAPK pathways were set in motion under hypotension, but not all branches. Only the p38 inhibitor can inhibit AQP5 expression in cultured astrocytes. AQP5 is directly related to the extracellular hypotonic stimuli in astrocytes, which could be regulated through the p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Background: Gait disruption is a common poststroke problem. Robot-assisted gait training (RAGT) might improve motor function, balance, and activities of daily living. Objective: We compared the clinical effectiveness of early integrated RAGT using the Walkbot robotic gym with an intensity-matched enhanced lower limb therapy (ELLT) program and with conventional rehabilitation therapy (CRT) in patients with acute ischemic stroke. Methods: A total of 192 patients with acute ischemic stroke were randomly assigned (1:1:1) to receive RAGT, ELLT, or CRT. All three groups received 45 min of training daily, 3 days a week, for 4 weeks consecutively. Before and after the 4-week treatment, the patients were assessed based on a 6-minute walking test (6MWT), functional ambulation classification (FAC), timed up and go (TUG) test, dual-task walking (DTW) test, Tinetti's test, Barthel's index (BI), stroke-specific quality of life (SS-QOL) scale, and gait analysis parameters. Results: After the 4-week intervention, the results of the 6MWT, FAC, TUG, DTW, Tinetti's test, BI, SS-QOL, and gait in the three groups significantly improved. Compared with ELLT and CRT groups, participants in the RAGT group had a better performance in 6MWT (199.11 ± 60.72 versus 182.47 ± 59.72 versus 173.69 ± 40.58, p = 0.035), FAC (4.10 ± 0.91 versus 3.69 ± 0.88 versus 3.58 ± 0.81, p = 0.044), DTW (10.29 ± 2.38 versus 12.92 ± 2.64 versus 13.89 ± 2.62, p = 0.031), SS-QOL (184.46 ± 20.53 versus 165.39 ± 20.49 versus 150.72 ± 20.59, p = 0.012), velocity (0.66 ± 0.22 versus 0.55 ± 0.23 versus 0.51 ± 0.20, p = 0.008), cycle duration (1.38 ± 0.40 versus 1.50 ± 0.38 versus 1.61 ± 0.30, p = 0.040), and swing phase symmetry ratio (SPSR, 1.10 ± 0.33 versus 1.21 ± 0.22 versus 1.48 ± 0.25, p = 0.021). The TUG, Tinetti's test, BI, and RMT results were similar, however. Conclusion: In the acute stroke phase, early integrated RAGT showed greater performance in gait rehabilitation than CRT and ELLT. Registration: ChiCTR1900026225 [ABSTRACT FROM AUTHOR]

Activity-regulated cytoskeleton-associated protein (ARC) is activated by the induction of long-term potentiation and plays an important role in the synaptic plasticity of memory consolidation. Previous studies have shown that abnormal expression of ARC in the brains of patients with Alzheimer's Disease (AD) leads to the disturbance of synaptic plasticity. ARC expression is mainly regulated by transcriptional and post-translational modification. However, it is unclear whether N6-methyladenosine (m6A) engages in the epigenetic modification of ARC. The AlzData database was used to analyze the brain of AD patients, and Aβ-induced cell models were used. We revealed that ARC expression was reduced in AD patients and Aβ-induced cell models. There were five m6A modification sites of ARC mRNA that were predicted by the SRAMP database, and ARC mRNA was confirmed as the target gene of methyltransferase-like 3 (METTL3) by MeRIP. Amyloid-beta protein (Aβ) repressed the m6A modification. Knockdown of METTL3 decreased ARC mRNA m6A modification and reduced ARC protein expression, while overexpression of METTL3 rescued ARC expression after Aβ treatment. Knockdown of YTH domain family, member 1 (YTHDF1) decreased ARC protein expression, while the overexpression of YTHDF1 could not rescue the loss of ARC protein expression after 3-deazaadenosine treatment or knockdown of METTL3. Our findings identify that METTL3 rescues the Aβ-induced reduction of ARC expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD. [ABSTRACT FROM AUTHOR]

Objective: The aim was to study whether the computed tomography (CT) density and β-amyloid (Aβ) level of intraorbital optic nerve could assist in diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: A total of sixty subjects were recruited in our study, including nine normal control (NC) subjects (i.e., 4 men and 5 women), twenty four MCI subjects (i.e., 11 men and 13 women), and twenty seven AD subjects (i.e., 14 men and 13 women). All subjects conducted 18F-flutemetamol amyloid positron emission tomography (PET)/CT imaging. Blinded to the clinical information of the subjects, two physicians independently measured and calculated the standardized uptake value ratio (SUVR) of the bilateral occipital cortex, SUVR of the bilateral intraorbital optic nerve, and CT density of the bilateral intraorbital optic nerve by using GE AW 4.5 Workstation. Results: Between AD and NC groups, the differences of the bilateral intraorbital optic nerve SUVR were statistically significant; between AD and MCI groups, the differences of the left intraorbital optic nerve SUVR were statistically significant. Between any two of the three groups, the differences in the bilateral intraorbital optic nerve density were statistically significant. The bilateral occipital SUVR was positively correlated with the bilateral intraorbital optic nerve SUVR and negatively correlated with the bilateral intraorbital optic nerve density. Bilateral intraorbital optic nerve SUVR was negatively correlated with the bilateral intraorbital optic nerve density. The area under the receiver operating characteristic (ROC) curve of multiple logistic regression was 0.9167 (for MCI vs. NC) and 0.8951 (for AD vs. MCI). The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores were positively associated with the intraorbital optic nerve density and were negatively associated with the intraorbital optic nerve SUVR. The regression equation of MoCA was y = 16.37-0.9734 × x 1 + 0.5642 × x 2-3.127 × x 3 + 0.0275 × x 4; the R 2 was 0.848. The regression equation of MMSE was y = 19.57-1.633 × x 1 + 0.4397 × x 2-1.713 × x 3 + 0.0424 × x 4; the R 2 was 0.827. Conclusion: The CT density and Aβ deposition of the intraorbital optic nerve were associated with Aβ deposition of the occipital cortex and the severity of cognitive impairment. The intraorbital optic nerve CT density and intraorbital optic nerve Aβ deposition could assist in diagnosing MCI and AD. [ABSTRACT FROM AUTHOR]

Increased sympathetic nervous activity is one of main contributors to pathogenesis and progression of hypertension. Renal denervation (RDN) has been demonstrated as a potential therapy for treatment of hypertension; however, lack of indicators of intra-/post-procedure results in inconsistent clinical outcomes. Renal nerve stimulation (RNS), a simple and promising method, could evoke elevated blood pressure as an intraoperative indicator for RDN. But related researches on patterns of blood pressure responses to RNS are still incomplete. To investigate and categorize the phenotypes of blood pressure response to RNS and heart rate alteration before and after RNS, 24 Chinese Kunming dogs were used to perform RNS from bifurcation to ostium of renal arteries after angiography, and a total of 483 stimulated sites were complete. We identified five different patterns of blood pressure response to RNS in 483 stimulated sites, (1) continuous ascending and finally keeping steady above baseline (26.9%), (2) declining and then rising over baseline (11.8%), (3) declining and then rising but below baseline (14.5%), (4) fluctuating in the vicinity of baseline (39.5%), and (5) continuous declining and finally keeping steady below baseline (7.2%), and found no difference in RR intervals among five blood pressure responses before and after renal nerve stimulation. Renal nerve stimulation could elicit different patterns of blood pressure response, which could potentially assist in distinguishing sympathetic-excitatory sites and sympathetic-inhibitory sites from mixed nerve components, which might help to improve the efficacy of RDN. [ABSTRACT FROM AUTHOR]

Background and Objective. White matter lesions (WMLs) are imaging changes characterized by hyperintensities on T2-weighted or FLAIR images, which are closely related to the decline of cognitive function. However, the etiology and pathogenesis of WMLs remain undetermined. The aim of this study was to analyze the relationship between adiponectin levels and cognitive decline in persons with or without white matter lesions. Method. In the present study, 126 patients, 90 cases in the WML group and 36 cases in the control group, were analyzed to explore the relationship between adiponectin and WMLs. All patients underwent an MRI scan to assess whether white matter lesions happened. And the serum levels of adiponectin were detected by ELISA. Results. In this study, according to Fazekas criteria, WMLs were divided into different severity groups. With the increase of WML score, the level of adiponectin decreased, and linear correlation analysis shows that adiponectin is negatively correlated with the severity of white matter lesions (p < 0.001). And adiponectin level was significantly positively correlated with MoCA score (p < 0.05). Moreover, adiponectin in the WMLs combined with the cognitive impairment group was significantly reduced (p < 0.01). Conclusion. The level of adiponectin is independently associated with WMLs and cognitive function, which suggests that adiponectin may be a protective factor for WMLs and cognitive function. [ABSTRACT FROM AUTHOR]

Background: Positional nystagmus induced by supine roll test is characteristic for diagnosing horizontal semicircular canal benign paroxysmal positional vertigo (HC-BPPV). In this study, we aimed to explore the value of nystagmus parameters in by supine roll test (SRT) as prognostic factors in HC-BPPV. Methods: We retrospectively analyzed the nystagmus parameters of 813 patients diagnosed with HC-BPPV by the SRT model in the SRM-IV system through video nystagmography. Then we used the computer-controlled canalith repositioning procedure (CCRP) mode for treatment. Based on the outcomes, patients were divided into either the cured group or the resistant group. The 1:1 propensity score matching (PSM) was applied to minimize potential selection bias. Then univariable and multivariable analyses were performed to identify the association of nystagmus parameters and the efficacy of CCRP. Results: Among the 813 patients, 99 (12.2%) were classified in the resistant group. The right side of HC-BPPV patients was twice the number of the left side patients (537 vs. 276). PSM is used to pair resistant patients to the cured patients, in which 99 pairs were successfully matched. Results of univariate and multivariate analyses showed that patients in the resistant group have longer latency in the affected side [odds ratio (OR) = 1.231 (1.110–1.366); P < 0.001] and slower slow phase velocity (SPV) in the healthy side [OR = 0.957 (0.917–0.999); P = 0.045]. Conclusion: Nystagmus parameters may represent the characteristics of canalith. HC-BPPV patients with a longer latency in the affected side and slower SPV on the healthy side during SRT have a higher risk of HC-BPPV persisting after a single CCRP. [ABSTRACT FROM AUTHOR]

Background: The prevalence of mild cognitive impairment (MCI), herein China, was without involving the suburban communities, where the awareness of MCI still remains extremely weak.Objective: The objective of this study is to investigate the prevalence of MCI in the Chinese residents aged ≥65 in the suburban communities of Shanghai, China, and study the awareness of MCI in terms of its symptom, prevention, and intervention.Methods: A total of 925 suburban community residents aged ≥65 were evaluated with a series of clinical examinations and scale questionnaire, and 600 participated in a five-dimension questionnaire survey pertaining to the awareness of MCI.Results: The prevalence of MCI was up to 29.8% and of dementia was 11.1%, respectively. A difference was observed among the three groups of dementia, MCI, and normal in each dimension of age, gender, education, being widowed, and living with the next generation (P < 0.05). The degree of cognitive impairment was linearly correlated with age (P < 0.001). The prevalence of MCI was higher in the females (P < 0.001), in the group of low educational level (P < 0.001), in the widowed residents (P < 0.01), and in those who did not live with their next generations (P < 0.01). The family's concern for MCI symptoms in the elderly accounted for 60%; the awareness rate of MCI symptoms, 25.5%; the awareness rate of MCI prevention, 15.5%; and the rate of taking MCI seniors to the doctor, 32%.Conclusions: The prevalence of MCI in the suburban communities of Shanghai was high but the awareness of MCI was low. [ABSTRACT FROM AUTHOR]

The ratio of excitatory to inhibitory neurotransmitters is essential for maintaining the firing patterns of neural networks, and is strictly regulated within individual neurons and brain regions. Excitatory to inhibitory (E/I) imbalance has been shown to participate in the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Glutamate excitotoxicity and GABAergic neuron dysfunction appear to be key components of the neuronal cell death that takes place in AD. Since extracellular vesicles (EVs) are now explored as an important vehicle in transmitting signals between cells, we hypothesized that the function of neuron-derived small EVs (sEVs) might be regulated by the status of neurotransmitter balance and that sEVs might affect amyloid β (Aβ) toxicity on neurons. This study aimed to reveal the effects of sEVs from unbalanced neurotransmitter-stimulated neurons on Aβ-induced toxicity. We demonstrated the opposite effects of the two groups of sEVs isolated from neurons stimulated by glutamate or GABA on Aβ toxicity in vivo and in vitro. The sEVs released from GABA-treated neurons alleviated Aβ-induced damage, while those released from glutamate-treated neurons aggravated Aβ toxicity. Furthermore, we compared the microRNA (miRNA) composition of sEVs isolated from glutamate/GABA/PBS-treated neurons. Our results showed that glutamate and GABA oppositely regulated miR-132 levels in sEVs, resulting in the opposite destiny of recipient cells challenged with Aβ. Our results indicated that manipulating the function of sEVs by different neurotransmitters may reveal the mechanisms underlying the pathogenesis of AD and provide a promising strategy for AD treatment. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background Male clients of female sex workers ('clients' hereafter) are considered high-risk and potentially a bridge population in the HIV epidemic. Non-occupational post-exposure prophylaxis (nPEP) is a safe and effective but under-utilised public health intervention to prevent HIV transmission. This study aims to explore clients' awareness of nPEP, intention of uptake, potential barriers to nPEP uptake and adherence, and suggestions for nPEP promotion in China.Methods: We conducted semi-structured in-depth interviews with 20 clients in two Chinese cities in 2018. Participants were recruited through purposive sampling. The content of the interviews was analysed using thematic content analysis in ATLAS.ti.Results: Overall, just a minority of participants were aware of nPEP. A majority expressed willingness to use nPEP. Potential barriers to nPEP uptake and adherence included adverse drug reactions, price, concerns of drug efficacy, privacy issues, and forgetting to take the drugs. Almost all participants expressed the need to promote nPEP among clients. Participants suggested that the promotion of nPEP should be at hospitals, online, and be integrated with HIV/AIDS health education.Conclusions: Our findings suggested that nPEP guidelines should be formulated and implementation strategies should be developed to address barriers to uptake and adherence in order to successfully tap into the potential of nPEP as an effective HIV prevention tool. [ABSTRACT FROM AUTHOR]

An easily scoring system to predict the risk of cognitive impairment after minor ischemic stroke has not been available. We aimed to develop and externally validate a nomogram for predicting the probability of post-stroke cognitive impairment (PSCI) among hospitalized population with minor stroke. Moreover, the association of Trimethylamine N-oxide (TMAO) with PSCI is also investigated. We prospectively conducted a developed cohort on collected data in stroke center from June 2017 to February 2018, as well as an external validation cohort between June 2018 and February 2019. The main outcome is cognitive impairment defined as <22 Montreal Cognition Assessment (MoCA) score points 6 – 12 months following a minor stroke onset. Based on multivariate logistic models, the nomogram model was generated. Plasma TMAO levels were assessed at admission using liquid chromatography tandem mass spectrometry. A total of 228 participants completed the follow-up data for generating the nomogram. After multivariate logistic regression, seven variables remained independent predictors of PSCI to compose the nomogram included age, female, Fazekas score, educational level, number of intracranial atherosclerotic stenosis (ICAS), HbA1c, and cortical infarction. The area under the receiver-operating characteristic (AUC-ROC) curve of model was 0.829, C index was good (0.810), and the AUC-ROC of the model applied in validation cohort was 0.812. Plasma TMAO levels were higher in patients with cognitive impairment than in them without cognitive dysfunction (median 4.56 vs. 3.22 μmol/L; p ≤ 0.001). In conclusion, this scoring system is the first nomogram developed and validated in a stroke center cohort for individualized prediction of cognitive impairment after minor stroke. Higher plasma TMAO level at admission suggests a potential marker of PSCI. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cotton bollworm, Helicoverpa armigera (Hübner), and the beet armyworm, Spodoptera exigua (Hübner), are two major polyphagous lepidopteran pests of cultivated crops. They develop various levels of resistance to many frequently applied broad‐spectrum insecticides. Here, the larval susceptibilities of a laboratory population and six field‐collected populations per pest from Hunan Province, China to three insecticides were determined using a standard leaf‐dipping method in the laboratory. Field‐plot trials were conducted to verify the control efficacies of broflanilide 100 g L−1 suspension concentrate (SC), chlorantraniliprole 5% SC and emamectin benzoate 5.7% water‐dispersible granule, against H. armigera and S. exigua larvae using foliar sprays in 2013 and 2019. RESULTS: Variations among H. armigera and S. exigua field populations in their susceptibility levels to the three insecticides were observed in Linli, Yueyang and Changsha counties from 2013 to 2019. They were still high susceptibility to broflanilide only, but developed low and/or moderate levels of resistance to chlorantraniliprole and emamectin benzoate. In addition, broflanilide at 25 g ha−1 provided an excellent control efficacy of 81.92% to 96.46% against these pests during the 3–14‐days period after treatment in both years, whereas chlorantraniliprole at 50 g ha−1 and emamectin benzoate at 4.5 g ha−1 exhibited significantly decreased efficacies, which were consistent with their corresponding toxicity levels. CONCLUSIONS: These results suggest that broflanilide should be an important new tool for the effective control of diamide‐ and avermectin‐resistant H. armigera and S. exigua. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This study aimed to investigate the long-term safety and benefits of antiplatelet therapy in patients with cerebral infarction with thrombocytopenia, as evidence regarding this was limited. This cohort trial assessed patients with acute cerebral infarction with thrombocytopenia treated in the Neurology Department of Shanghai Tenth People's Hospital from January 2016 to December 2018, and enrolled patients were followed up for 9 months. The patients were divided into non-antiplatelet and antiplatelet groups based on the actual intake of antiplatelet drugs. Primary endpoints included hemorrhagic events, recurrence of cerebral infarction, and activity of daily living (ADL) score changes. To balance baseline clinical data, propensity score matching was applied, and there were finally 65 matched patients, including 30 and 35 in the antiplatelet and non-antiplatelet groups, respectively. There were no differences in hemorrhagic and cerebral infarction recurrence rates between the 2 groups. ADL score change was higher in the antiplatelet group than in the non-antiplatelet group (10 vs 5, p = 0.039). In multivariate regression analysis, antiplatelet therapy significantly predicted a positive change in ADL scores [B = 8.381, 95% confidence interval (0.56-16.19)]. In patients with acute cerebral infarction with thrombocytopenia, antiplatelet therapy could the improve the quality of life in the chronic stage. [ABSTRACT FROM AUTHOR]

Microglia activation contributes to Alzheimer's disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN. [ABSTRACT FROM AUTHOR]

In this letter, a combination of multi-gate field effect transistor with ferroelectric is proposed for a new concept of memory merged logic device. For the first time, dual-gate MoS2 field effect transistor (FET) with a Hf0.5Zr0.5O2 (HZO) back gate insulator is fabricated. Because of the manipulation of charge density in the channel by both electric field from the top/back gates and the polarization field form the HZO, the ferroelectric embedded dual-gate (FEDG) MoS2 FET can work as a normal n-type top-gate MOSFET or a ferroelectric memory with 1 V memory window and retention time up to 103 s, separately or simultaneously. In memory merged logic operation, the output current of the devices depends on the top-gate voltage, back-gate voltage and the polarization of the HZO, which greatly extend the possible function that one transistor can implement. The FEDG FET has the benefits of diminishing the power dissipation of inter connection between logic and memory arrays in the integrated circuit, and reducing the number of transistors in circuits comparing to standard MOSFET configurations, which shows a great potential in the ultra-low power consumption in memory computing (IMC) and neuromorphic computing (NC) applications. [ABSTRACT FROM AUTHOR]