AMPK exerts dual regulatory effects on the PI3K pathway

BACKGROUND AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated when cells experience energy deficiency and conversely suppressed in surfeit of energy supply. AMPK activation improves insulin sensitivity via multiple mechanisms, among which AMPK suppresses mTOR/S6K-mediated negative feedback regulation of insulin signaling. RESULTS In the present study we further investigated the mechanism of AMPK-regulated insulin signaling. Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside (AICAR) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1)-associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin-stimulated activation of mTOR was diminished. In 3T3-F442a preadipocytes, these effects were attenuated by expression of a dominant negative mutant of AMPK α1 subunit. The enhancing effect of ACIAR on Akt phosphorylation was also observed when the cells were treated with EGF, suggesting that it is regulated at a step beyond IR/IRS1. Indeed, when the cells were chronically treated with AICAR in the absence of insulin, Akt phosphorylation was progressively increased. This event was associated with an increase in levels of phosphatidylinositol -3,4,5-trisphosphate (PIP3) and blocked by Wortmannin. We then expressed the dominant negative mutant of PTEN (C124S) and found that the inhibition of endogenous PTEN per se did not affect phosphorylation of Akt at basal levels or upon treatment with AICAR or insulin. Thus, this result suggests that AMPK activation of Akt is not mediated by regulating phosphatase and tensin homologue (PTEN). CONCLUSION Our present study demonstrates that AMPK exerts dual effects on the PI3K pathway, stimulating PI3K/Akt and inhibiting mTOR/S6K.National Institutes of Health (CA118918, GM057959

Accelerating Vertical Federated Learning

Privacy, security and data governance constraints rule out a brute force process in the integration of cross-silo data, which inherits the development of the Internet of Things. Federated learning is proposed to ensure that all parties can collaboratively complete the training task while the data is not out of the local. Vertical federated learning is a specialization of federated learning for distributed features. To preserve privacy, homomorphic encryption is applied to enable encrypted operations without decryption. Nevertheless, together with a robust security guarantee, homomorphic encryption brings extra communication and computation overhead. In this paper, we analyze the current bottlenecks of vertical federated learning under homomorphic encryption comprehensively and numerically. We propose a straggler-resilient and computation-efficient accelerating system that reduces the communication overhead in heterogeneous scenarios by 65.26% at most and reduces the computation overhead caused by homomorphic encryption by 40.66% at most. Our system can improve the robustness and efficiency of the current vertical federated learning framework without loss of security

Beneficial effects of baicalein on a model of allergic rhinitis

Allergic rhinitis (AR) is a common disease that causes severe inflammation and even disabilities. Previous studies have reported baicalein to have an anti-inflammatory effect. However, the pharmacological action of baicalein on anaphylaxis has not been clarified yet. This study assessed the in vivo protective effect of baicalein post-treatment in an ameliorating ovalbumin (OVA)-sensitized AR rat model. Baicalein attenuated histological alterations, aberrant tissue repair and inflammation after OVA-induced AR. Baicalein reduced the frequency of nasal/ear rubs and sneezes in rats, and inhibited generation of several inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both blood and nasal lavage of rats. Infiltrations of eosinophils, lymphocyte, and neutrophils were decreased in baicalein-administered rats. Furthermore, baicalein inhibited the expression of STAT3 phosphorylation in the nasal mucosa. In summary, baicalein attenuated OVA-induced AR and inflammation, which suggests it as a promising therapeutic agent for the alleviation of AR-associated inflammation and pathology

Ship Intention Prediction at Intersections Based on Vision and Bayesian Framework

Due to the high error frequency of the existing methods in identifying a ship’s navigational intention, accidents frequently occur at intersections. Therefore, it is urgent to improve the ability to perceive ship intention at intersections. In this paper, we propose an algorithm based on the fusion of image sequence and radar information to identify the navigation intention of ships at intersections. Some existing algorithms generally use the Automatic Identification System (AIS) to identify ship intentions but ignore the problems of AIS delay and data loss, resulting in unsatisfactory effectiveness and accuracy of intention recognition. Firstly, to obtain the relationship between radar and image, a cooperative target composed of a group of concentric circles and a central positioning radar angle reflector is designed. Secondly, the corresponding relationship of radar and image characteristic matrix is obtained after employing the RANSAC method to fit radar and image detection information; then, the homographic matrix is solved to realize radar and image data matching. Thirdly, the YOLOv5 detector is used to track the ship motion in the image sequence. The visual measurement model based on continuous object tracking is established to extract the ship motion parameters. Finally, the motion intention of the ship is predicted by integrating the extracted ship motion features with the position information of the shallow layer using a Bayesian framework. Many experiments on real data sets show that our proposed method is superior to the most advanced method for ship intention identification at intersections

Coupling Effects of Sandstorm and Dust from Coal Bases on the Atmospheric Environment of Northwest China

The coupling effects of sandstorm and dust from coal bases themselves can have a major impact on the atmospheric environment as well as on human health. The typical coal resource city of Wuhai in Inner Mongolia was selected in order to study these impacts during a severe sandstorm event in March 2021. Particulate matter (PM1, PM2.5 and PM10) and total suspended particulate matter (TSP) samples were collected during the sandstorm event of 15–19 March 2021 and non-sandstorm weather (11–13 March 2021) and analyzed for their chemical composition. The concentrations of PM1, PM2.5, PM10 and TSP in Wuhai city during the sandstorm were 2.2, 2.6, 4.8 and 6.0 times higher than during non-sandstorm days, respectively. Trace metals concentrations in particles of different sizes generally increased during the sandstorm, while water-soluble ions decreased. Positive matrix fraction (PMF) results showed that the main sources of particles during both sandstorm and non-sandstorm days were industrial emissions, traffic emissions, combustion sources and dust. The proportion of industrial emissions and combustion sources increased compared with non-sandstorm days, while traffic emissions and dust decreased. The backward trajectory analysis results showed that airflows were mainly transported over short distances during non-sandstorm days, and high concentration contribution source areas were from southern Ningxia, southeast Gansu and western Shaanxi. The airflow was mainly transported over long distances during the sandstorm event, and high concentration contribution source areas were from northwestern Inner Mongolia, southern Russia, northern and southwestern Mongolia, and northern Xinjiang. A health risk analysis showed that the risk to human health during sandstorm days related to the chemical composition of particles was generally 1.2–13.1 times higher than during non-sandstorm days. Children were more susceptible to health risks, about 2–6.3 times more vulnerable than adults to the risks from heavy metals in the particles under both weather conditions

Study on hot deformation behavior of homogenized Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr alloy using a combination of strain-compensated Arrhenius constitutive model and finite element simulation method

Isothermal hot compression experiments were conducted on homogenized Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr alloy to investigate hot deformation behavior at the temperature range of 673–773 K and the strain rate range of 0.001–1 s−1 by using a Gleeble-1500D thermo mechanical simulator. Metallographic characterization on samples deformed to true strain of 0.70 illustrates the occurrence of flow localization and/or microcrack at deformation conditions of 673 K/0.01 s−1, 673 K/1 s−1 and 698 K/1 s−1, indicating that these three deformation conditions should be excluded during hot working of homogenized Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr alloy. Based on the measured true stress-strain data, the strain-compensated Arrhenius constitutive model was constructed and then incorporated into UHARD subroutine of ABAQUS software to study hot deformation process of homogenized Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr alloy. By comparison with measured force-displacement curves, the predicted results can describe well the rheological behavior of homogenized Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr alloy, verifying the validity of finite element simulation of hot compression process with this complicated constitutive model. Numerical results demonstrate that the distribution of values of material parameters (α, n, Q and ln A) within deformed sample is inhomogeneous. This issue is directly correlated to the uneven distribution of equivalent plastic strain due to the friction effect. Moreover, at a given temperature the increase of strain rate would result in the decrease of equivalent plastic strain within the central region of deformed sample, which hinders the occurrence of dynamic recrystallization (DRX)

Numerical Investigation of Flow and Flame Structures in an Industrial Swirling Inverse Diffusion Methane/Air Burner

In this study, a novel gas burner combining air swirl and an inverse diffusion flame (IDF) is designed for industrial applications. Numerical simulations using the Reynolds-averaged Navier–Stokes (RANS) method and simplified reaction mechanisms are conducted to predict the turbulent flow and combustion performance of the burner. Detailed flow structures, flame structures and effects of burner configurations are examined. The simulation results indicate that the swirl action of the burner creates a central recirculation zone and two external recirculation zones at the burner head, which stabilize combustion. The tangential velocity is minimal at the center of the burner and decreases with increasing distance from the outlet. As the distance from the exit increases, the maximum tangential velocity gradually decreases, and the peak value shifts towards the wall. This decrease in tangential velocity with axial distance signifies the gradual dissipation of the swirl effect, which disappears near the chamber outlet. The comparisons reveal that altering the number of burner fuel nozzles is more effective in reducing NO emissions than changing the inclination angle of the fuel nozzles, in the given conditions. Favorable combustion conditions are achieved when there are 16 fuel nozzles and the nozzle inclination angle is 60°, resulting in a 28.5% reduction in NO emissions at the outlet, compared to the reference condition

27-Hydroxycholesterol-Induced Dysregulation of Cholesterol Metabolism Impairs Learning and Memory Ability in ApoE ε4 Transgenic Mice

Dysregulated brain cholesterol metabolism is one of the characteristics of Alzheimer’s disease (AD). 27-Hydroxycholesterol (27-OHC) is a cholesterol metabolite that plays an essential role in regulating cholesterol metabolism and it is suggested that it contributes to AD-related cognitive deficits. However, the link between 27-OHC and cholesterol homeostasis, and how this relationship relates to AD pathogenesis, remain elusive. Here, 12-month-old ApoE ε4 transgenic mice were injected with saline, 27-OHC, 27-OHC synthetase inhibitor (anastrozole, ANS), and 27-OHC+ANS for 21 consecutive days. C57BL/6J mice injected with saline were used as wild-type controls. The indicators of cholesterol metabolism, synaptic structure, amyloid β 1-42 (Aβ1-42), and learning and memory abilities were measured. Compared with the wild-type mice, ApoE ε4 mice had poor memory and dysregulated cholesterol metabolism. Additionally, damaged brain tissue and synaptic structure, cognitive decline, and higher Aβ1-42 levels were observed in the 27-OHC group. Moreover, cholesterol transport proteins such as ATP-binding cassette transporter A1 (ABCA1), apolipoprotein E (ApoE), low-density lipoprotein receptor (LDLR), and low-density lipoprotein receptor-related protein1 (LRP1) were up-regulated in the cortex after the 27-OHC treatment. The levels of cholesterol metabolism-related indicators in the hippocampus were not consistent with those in the cortex. Additionally, higher serum apolipoprotein A1 (ApoA1) levels and lower serum ApoE levels were observed in the 27-OHC group. Notably, ANS partially reversed the effects of 27-OHC. In conclusion, the altered cholesterol metabolism induced by 27-OHC was involved in Aβ1-42 deposition and abnormalities in both the brain tissue and synaptic structure, ultimately leading to memory loss in the ApoE ε4 transgenic mice

Regulation of Th17/Treg Balance by 27-Hydroxycholesterol and 24S-Hydroxycholesterol Correlates with Learning and Memory Ability in Mice

Dysregulation of cholesterol metabolism and its oxidative products—oxysterols—in the brain is known to be associated with neurodegenerative diseases. It is well-known that 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC) are the main oxysterols contributing to the pathogenesis of Alzheimer’s disease (AD). However, the molecular mechanism of how 27-OHC and 24S-OHC cause cognitive decline remains unclear. To verify whether 27-OHC and 24S-OHC affect learning and memory by regulating immune responses, C57BL/6J mice were subcutaneously injected with saline, 27-OHC, 24S-OHC, 27-OHC+24S-OHC for 21 days. The oxysterols level and expression level of related metabolic enzymes, as well as the immunomodulatory factors were measured. Our results indicated that 27-OHC-treated mice showed worse learning and memory ability and higher immune responses, but lower expression level of interleukin-10 (IL-10) and interferon (IFN-λ2) compared with saline-treated mice, while 24S-OHC mice performed better in the Morris water maze test than control mice. No obvious morphological lesion was observed in these 24S-OHC-treated mice. Moreover, the expression level of interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 3α (MIP-3α) were significantly decreased after 24S-OHC treatment. Notably, compared with 27-OHC group, mice treated with 27-OHC+24S-OHC showed higher brain 24S-OHC level, accompanied by increased CYP46A1 expression level while decreased CYP7B1, retinoic acid-related orphan receptor gamma t (RORγt) and IL-17A expression level. In conclusion, our study indicated that 27-OHC is involved in regulating the expression of RORγt, disturbing Th17/Treg balance-related immune responses which may be associated with the learning and memory impairment in mice. In contrast, 24S-OHC is neuroprotective and attenuates the neurotoxicity of 27-OHC

Controllable Fabrication of Pyramidal Silicon Nanopore Arrays and Nanoslits for Nanostencil Lithography

This paper presents a controllable method for the high-throughout fabrication of pyramidal silicon nanopore arrays (PSNAs). Using this method, square nanopore arrays with an average size of 60 nm, rectangular nanopores with different length–width ratios, and nanoslits with feature sizes as small as 13 nm were created. Focused ion beam (FIB) cutting experiments showed that the inner structure of the nanopore was exactly pyramidal, which offered unique ionic rectification properties. Moreover, preliminary nanostencil lithography experiments indicated that such PSNAs could be used as reusable masks to directly deposit large-scale surface patterns in both nano and micro scales, and with less time and low cost