Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes.

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation.

Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction.

polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson's disease and Crohn's disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson's disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD.

DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response.

The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation.

High biocompatible FITC-conjugated silica nanoparticles for cell labeling in both in vitro and in vivo models.

Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells.

The effect of facial colour on implicit facial expressions.

Humans recognise reddish-coloured faces as angry. However, does facial colour also affect "implicit" facial expression perception of which humans are not explicitly aware? In this study, we investigated the effects of facial colour on implicit facial expression perception. The experimental stimuli were "hybrid faces", in which the low-frequency component of the neutral facial expression image was replaced with the low-frequency component of the facial expression image of happiness or anger.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

Introduction: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC.

CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys.

A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models.

Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody.

Vehicular Platoon Communication: Architecture, Security Threats and Open Challenges.

The emerging technology that is vehicular platooning is an exciting technology. It promises to save space on congested roadways, improve safety and utilise less fuel for transporting goods, reducing greenhouse gas emissions. The technology has already been shown to be vulnerable to attack and exploitation by attackers.

Molecular architecture determines brain delivery of a transferrin receptor-targeted lysosomal enzyme.

Delivery of biotherapeutics across the blood-brain barrier (BBB) is a challenge. Many approaches fuse biotherapeutics to platforms that bind the transferrin receptor (TfR), a brain endothelial cell target, to facilitate receptor-mediated transcytosis across the BBB. Here, we characterized the pharmacological behavior of two distinct TfR-targeted platforms fused to iduronate 2-sulfatase (IDS), a lysosomal enzyme deficient in mucopolysaccharidosis type II (MPS II), and compared the relative brain exposures and functional activities of both approaches in mouse models.

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the iduronate-2-sulfatase (IDS) enzyme, resulting in cellular accumulation of glycosaminoglycans (GAGs) throughout the body. Treatment of MPS II remains a considerable challenge as current enzyme replacement therapies do not adequately control many aspects of the disease, including skeletal and neurological manifestations. We developed an IDS transport vehicle (ETV:IDS) that is engineered to bind to the transferrin receptor; this design facilitates receptor-mediated transcytosis of IDS across the blood-brain barrier and improves its distribution into the brain while maintaining distribution to peripheral tissues.

Linh Phu Khang Tue Tinh inhibited prostate proliferation in rats induced benign prostatic hyperplasia by testosterone propionate.

Ethnopharmacological Relevance: Benign prostatic hyperplasia (BPH) is the hyperproliferation of the stromal and the epithelial cells within the prostatic transition zone. In recent years, phytotherapy have been studied with the concern for increasing quality of life, improving lower urinary tract symptoms (LUTS) as well as reducing prostate volume and the frequency of adverse events was similar to that of placebo. Linh Phu Khang Tue Tinh (LPKTT) capsules are formulated from 4 herbs widely used in traditional Vietnamese medicine - Panax notoginseng (Burkill) F.

Causes and Clinical Characteristics of Small Bowel Bleeding in Northern Vietnam.

Aim: Causes, clinical features, and diagnostic approaches for small bowel (SB) bleeding were analyzed to derive recommendations in dealing with this clinical condition.

Methods: We included 54 patients undergoing surgical treatment for SB bleeding, from January 2009 to December 2019. Detailed clinical data, diagnosis procedures, and causes of bleeding were collected.

Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice.

Blood-brain barrier (BBB) dysfunction underlies the pathogenesis of many neurological diseases. Platelet-derived growth factor receptor-alpha (PDGFRα) induces hemorrhagic transformation (HT) downstream of tissue plasminogen activator in thrombolytic therapy of acute stroke. Thus, PDGFs are attractive therapeutic targets for BBB dysfunction.

Characterization of Fluid Biomarkers Reveals Lysosome Dysfunction and Neurodegeneration in Neuronopathic MPS II Patients.

Mucopolysaccharidosis type II is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and characterized by the accumulation of the primary storage substrate, glycosaminoglycans (GAGs). Understanding central nervous system (CNS) pathophysiology in neuronopathic MPS II (nMPS II) has been hindered by the lack of CNS biomarkers. Characterization of fluid biomarkers has been largely focused on evaluating GAGs in cerebrospinal fluid (CSF) and the periphery; however, GAG levels alone do not accurately reflect the broad cellular dysfunction in the brains of MPS II patients.

Inaugural experience and early results of minimally invasive approach in cardiac surgery in Auvergne region, France.

Minimally invasive approach in cardiac surgery has become an established and common technique in many cardiac surgery centres throughout the world. We report how we safely introduced minimally invasive approach in cardiac surgery in our department and we aim to demonstrate that this approach is feasible in any medium-size cardiac surgical centre. it consisted of retrospective and descriptive study on 60 patients who underwent minimally invasive mitral valve (45) or aortic valve surgery (15) from January 2017 to Februry 2018.

EYES ABSENT and TIMELESS integrate photoperiodic and temperature cues to regulate seasonal physiology in .

Organisms possess photoperiodic timing mechanisms to detect variations in day length and temperature as the seasons progress. The nature of the molecular mechanisms interpreting and signaling these environmental changes to elicit downstream neuroendocrine and physiological responses are just starting to emerge. Here, we demonstrate that, in , EYES ABSENT (EYA) acts as a seasonal sensor by interpreting photoperiodic and temperature changes to trigger appropriate physiological responses.

Some Key Factors Affecting Consumers' Intentions to Purchase Functional Foods: A Case Study of Functional Yogurts in Vietnam.

The development of functional foods is key to promoting a healthy diet and preventing certain diseases. This study aims to examine several key factors that affect consumer attitude and intention with respect to purchasing functional foods in an emerging market economy. A research model was developed by extension of the Theory of Reasoned Action (TRA), and then validated through obtaining data from 596 Vietnamese consumers who were interested in functional yogurts using an interviewer-administered questionnaire.

A Refined Simple First-Order Shear Deformation Theory for Static Bending and Free Vibration Analysis of Advanced Composite Plates.

A refined simple first-order shear deformation theory is developed to investigate the static bending and free vibration of advanced composite plates such as functionally graded plates. By introducing the new distribution shape function, the transverse shear strain and shear stress have a parabolic distribution across the thickness of the plates, and they equal zero at the surfaces of the plates. Hence, the new refined theory needs no shear correction factor.

An Efficient Beam Element Based on Quasi-3D Theory for Static Bending Analysis of Functionally Graded Beams.

In this paper, a 2-node beam element is developed based on Quasi-3D beam theory and mixed formulation for static bending of functionally graded (FG) beams. The transverse shear strains and stresses of the proposed beam element are parabolic distributions through the thickness of the beam and the transverse shear stresses on the top and bottom surfaces of the beam vanish. The proposed beam element is free of shear-looking without selective or reduced integration.

Population-based birth defects data in the United States, 2010-2014: A focus on gastrointestinal defects.

Background: Gastrointestinal defects are a phenotypically and etiologically diverse group of malformations. Despite their combined prevalence and clinical impact, little is known about the epidemiology of these birth defects. Therefore, the objective of the 2017 National Birth Defects Prevention Network (NBDPN) data brief was to better describe the occurrence of gastrointestinal defects.

Towards a threat assessment framework for apps collusion.

App collusion refers to two or more apps working together to achieve a malicious goal that they otherwise would not be able to achieve individually. The permissions based security model of Android does not address this threat as it is rather limited to mitigating risks of individual apps. This paper presents a technique for quantifying the collusion threat, essentially the first step towards assessing the collusion risk.