Upregulation of zinc transporter 2 in the blood-CSF barrier following lead exposure

Zinc (Zn) is an essential element for normal brain function; an abnormal Zn homeostasis in brain and the cerebrospinal fluid (CSF) has been implied in the etiology of Alzheimer's disease (AD). However, the mechanisms that regulate Zn transport in the blood-brain interface remain unknown. This study was designed to investigate Zn transport by the blood-CSF barrier (BCB) in the choroid plexus, with a particular focus on Zn transporter-2 (ZnT2), and to understand if lead (Pb) accumulation in the choroid plexus disturbed the Zn regulatory function in the BCB. Confocal microscopy, quantitative PCR and western blot demonstrated the presence of ZnT2 in the choroidal epithelia; ZnT2 was primarily in cytosol in freshly isolated plexus tissues but more toward the peripheral membrane in established choroidal Z310 cells. Exposure of rats to Pb (single ip injection of 50 mg Pb acetate/kg) for 24 h increased ZnT2 fluorescent signals in plexus tissues by confocal imaging and protein expression by western blot. Similar results were obtained by in vitro experiments using Z310 cells. Further studies using cultured cells and a two-chamber Transwell device showed that Pb treatment significantly reduced the cellular Zn concentration and led to an increased transport of Zn across the BCB, the effect that may be due to the increased ZnT2 by Pb exposure. Taken together, these results indicate that ZnT2 is present in the BCB; Pb exposure increases the ZnT2 expression in choroidal epithelial cells by a yet unknown mechanism and as a result, more Zn ions may be deposited into the intracellular Zn pool, leading to a relative Zn deficiency state in the cytoplasm at the BCB

ElegantSeg: End-to-End Holistic Learning for Extra-Large Image Semantic Segmentation

This paper presents a new paradigm for Extra-large image semantic Segmentation, called ElegantSeg, that capably processes holistic extra-large image semantic segmentation (ELISS). The extremely large sizes of extra-large images (ELIs) tend to cause GPU memory exhaustion. To tackle this issue, prevailing works either follow the global-local fusion pipeline or conduct the multi-stage refinement. These methods can only process limited information at one time, and they are not able to thoroughly exploit the abundant information in ELIs. Unlike previous methods, ElegantSeg can elegantly process holistic ELISS by extending the tensor storage from GPU memory to host memory. To the best of our knowledge, it is the first time that ELISS can be performed holistically. Besides, ElegantSeg is specifically designed with three modules to utilize the characteristics of ELIs, including the multiple large kernel module for developing long-range dependency, the efficient class relation module for building holistic contextual relationships, and the boundary-aware enhancement module for obtaining complete object boundaries. ElegantSeg outperforms previous state-of-the-art on two typical ELISS datasets. We hope that ElegantSeg can open a new perspective for ELISS. The code and models will be made publicly available

Prediction of hyperuricemia in people taking low-dose aspirin using a machine learning algorithm: a cross-sectional study of the National Health and Nutrition Examination Survey

Background: Hyperuricemia is a serious health problem related to not only gout but also cardiovascular diseases (CVDs). Low-dose aspirin was reported to inhibit uric acid excretion, which leads to hyperuricemia. To decrease hyperuricemia-related CVD, this study aimed to identify the risk of hyperuricemia in people taking aspirin.Method: The original data of this cross-sectional study were obtained from the National Health and Nutrition Examination Survey between 2011 and 2018. Participants who filled in the “Preventive Aspirin Use” questionnaire with a positive answer were included in the analysis. Six machine learning algorithms were screened, and eXtreme Gradient Boosting (XGBoost) was employed to establish a model to predict the risk of hyperuricemia.Results: A total of 805 participants were enrolled in the final analysis, of which 190 participants had hyperuricemia. The participants were divided into a training set and testing set at a ratio of 8:2. The area under the curve for the training set was 0.864 and for the testing set was 0.811. The SHapley Additive exPlanations (SHAP) method was used to evaluate the performances of the modeling. Based on the SHAP results, the feature ranking interpretation showed that the estimated glomerular filtration rate, body mass index, and waist circumference were the three most important features for hyperuricemia in individuals taking aspirin. In addition, triglyceride, hypertension, total cholesterol, high-density lipoprotein, low-density lipoprotein, age, race, and smoking were also correlated with the development of hyperuricemia.Conclusion: A predictive model established by XGBoost algorithms can potentially help clinicians make an early detection of hyperuricemia risk in people taking low-dose aspirin

Altered clearance of beta-amyloid from the cerebrospinal fluid following subchronic lead exposure in rats: Roles of RAGE and LRP1 in the choroid plexus

Formation of amyloid plaques is the hallmark of Alzheimer's disease. Our early studies show that lead (Pb) exposure in PDAPP transgenic mice increases β-amyloid (Aβ) levels in the cerebrospinal fluid (CSF) and hippocampus, leading to the formation of amyloid plaques in mouse brain. Aβ in the CSF is regulated by the blood-CSF barrier (BCB) in the choroid plexus. However, the questions as to whether and how Pb exposure affected the influx and efflux of Aβ in BCB remained unknown. This study was conducted to investigate whether Pb exposure altered the Aβ efflux in the choroid plexus from the CSF to blood, and how Pb may affect the expression and subcellular translocation of two major Aβ transporters, i.e., the receptor for advanced glycation end-products (RAGE) and the low density lipoprotein receptor protein-1 (LRP1) in the choroid plexus. Sprague-Dawley rats received daily oral gavage at doses of 0, 14 (low-dose), and 27 (high-dose) mg Pb/kg as Pb acetate, 5 d/wk, for 4 or 8 wks. At the end of Pb exposure, a solution containing Aβ40 (2.5 μg/mL) was infused to rat brain via a cannulated internal carotid artery. Subchronic Pb exposure at both dose levels significantly increased Aβ levels in the CSF and choroid plexus (p < 0.05) by ELISA. Confocal data showed that 4-wk Pb exposures prompted subcellular translocation of RAGE from the choroidal cytoplasm toward apical microvilli. Furthermore, it increased the RAGE expression in the choroid plexus by 34.1 % and 25.1 % over the controls (p < 0.05) in the low- and high- dose groups, respectfully. Subchronic Pb exposure did not significantly affect the expression of LRP1; yet the high-dose group showed LRP1 concentrated along the basal lamina. The data from the ventriculo-cisternal perfusion revealed a significantly decreased efflux of Aβ40 from the CSF to blood via the blood-CSF barrier. Incubation of freshly dissected plexus tissues with Pb in artificial CSF supported a Pb effect on increased RAGE expression. Taken together, these data suggest that Pb accumulation in the choroid plexus after subchronic exposure reduces the clearance of Aβ from the CSF to blood by the choroid plexus, which, in turn, leads to an increase of Aβ in the CSF. Interaction of Pb with RAGE and LRP1 in choroidal epithelial cells may contribute to the altered Aβ transport by the blood-CSF barrier in brain ventricles

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

An Improved Surface Treatment Process of 304 Stainless Steel Based on Low-Temperature Chromizing and Ultrasonic Vibration Extrusion

The ultrasonic vibration extrusion process is a widely used surface treatment process of stainless steel, e.g., 304 stainless steel, to improve the surface quality and increase hardness and wear resistance. However, for high-hardness 304 stainless steel, the traditional process, i.e., a single ultrasonic vibration extrusion process, does not fulfil its application requirements. To cope with this problem, this paper proposes an improved surface treatment method based on low-temperature chromizing and ultrasonic vibration extrusion to obtain the expected surface quality of 304 stainless steel. Using orthogonal design and multivariate regression, the influence of ultrasonic impact parameters on the surface integrity of 304 stainless steel was studied in this work. Finally, the experimental results show that the hardness of the surface processed by the proposed method is increased by about 2.55 times compared with the ultrasonic vibration extrusion process, and the surface roughness of the composite process is reduced by an average of 60.8% compared with that of unfinished surface. In addition, the optimal combination of process parameters is obtained: the spindle speed of 240 rpm, the feed of 0.1 mm/r, and the static extrusion of 40 μm, which can provide the optimal process parameter support for the surface treatment of 304 stainless steel

A Simple Miniature Ultra-Wide Band Magnetic Field Probe Design for Magnetic Near-Field Measurements

A simple miniature magnetic-field probe for near-field measurements in 9 kHz ~ 20 GHz bandwidth, which is applied to high-speed circuits, has been proposed and manufactured. The magnetic-field probe is built on a four-layer printed circuit board (PCB) using high-performance and low-loss Rogers material (εr =3.48 and tan δ =0.0037). Electric field coupling can be suppressed by PCB shielding structure of the magnetic-field probe. Coax-thru-hole via array technique is used to achieve impedance match. The resonance in working frequency band is suppressed through via fence, making |S21| rather smooth in the operation band. Experimental results show that the working frequency band is up to 9 kHz ~ 20 GHz