27 research outputs found

    Causal association between snoring and stroke: a Mendelian randomization study in a Chinese populationResearch in context

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    Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI <24.0 kg/m2), as well as multivariable MR (MVMR), were performed to control for potential pleiotropy from BMI. In addition, the inverse-variance weighted (IVW) method was applied to estimate the causal association with genetic variants identified in CKB GWAS. Findings: Positive associations were found between snoring and total stroke, hemorrhagic stroke (HS), and ischemic stroke (IS). With GRS of CKB, the corresponding HRs (95% CIs) were 1.56 (1.15, 2.12), 1.50 (0.84, 2.69), 2.02 (1.36, 3.01), and the corresponding HRs (95% CIs) using GRS of UKB were 1.78 (1.30, 2.43), 1.94 (1.07, 3.52), and 1.74 (1.16, 2.61). The associations remained stable in the MR among the non-obese group, MVMR analysis, and MR analysis using the IVW method. Interpretation: This study suggests that, among Chinese adults, genetically predicted snoring could increase the risk of total stroke, IS, and HS, and the causal effect was independent of BMI. Funding: National Natural Science Foundation of China, Kadoorie Charitable Foundation Hong Kong, UK Wellcome Trust, National Key R&D Program of China, Chinese Ministry of Science and Technology

    Effects of 60 days of 6° head-down bed rest on the composition and function of the human gut microbiota

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    Summary: Spaceflight is rigorous and dangerous environment which can negatively affect astronauts’ health and the entire mission. The 60 days of 6° head-down bed rest (HDBR) experiment provided us with an opportunity to trace the change of gut microbiota under simulated microgravity. The gut microbiota of volunteers was analyzed and characterized by 16S rRNA gene sequencing and metagenomic sequencing. Our results showed that the composition and function of the volunteers’ gut microbiota were markedly was affected by 60 days of 6° HDBR. We further confirmed the species and diversity fluctuations. Resistance and virulence genes in the gut microbiota were also affected by 60 days of 6° HDBR, but the species attributions remained stable. The human gut microbiota affected by 60 days of 6° HDBR which was partially consistent with the effect of spaceflight, this implied that HDBR was a simulation of how spaceflight affects the human gut microbiota

    HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation

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    Abstract Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoblast function play critical roles in bone formation, which is a highly regulated process. Long noncoding RNAs (lncRNAs) perform diverse functions in a variety of biological processes, including BMSC osteogenic differentiation. Although several studies have reported that HOX transcript antisense RNA (HOTAIR) is involved in BMSC osteogenic differentiation, its effect on bone formation in vivo remains unclear. Here, by constructing transgenic mice with BMSC (Prx1-HOTAIR)- and osteoblast (Bglap-HOTAIR)-specific overexpression of HOTAIR, we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo. Specifically, Prx1-HOTAIR mice showed delayed bone formation, while Bglap-HOTAIR mice showed increased bone formation. HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro. Furthermore, we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts. HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation. We first identified that the RNA-binding protein human antigen R (HuR) is responsible for HOTAIR nucleocytoplasmic translocation. HOTAIR is essential for osteoblast function, and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function. Bglap-HOTAIR mice, but not Prx1-HOTAIR mice, showed alleviation of bone loss induced by unloading. This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation, which provides new insights into precise regulation as a target for bone loss

    Stimulus-driven liquid metal and liquid crystal network actuators for programmable soft robotics

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    Sophisticated soft matter engineering has been endorsed as an emerging paradigm for developing untethered soft robots with built-in electronic functions and biomimetic adaptation capacities. However, the integration of flexible electronic components into soft robotic actuators is challenging due to strain mismatch and material incompatibilities. Herein, we report a general strategy to integrate electrically conductive liquid metals (LMs) and shape-morphing liquid crystal networks (LCNs) towards multifunctional and programmable soft robotics. A unique colloidal LM ink with superior adhesion and photothermal conversion efficiency was judiciously designed and fabricated by ultrasonicating LMs and miniature carboxylated gold nanorods (MiniGNR-COOH) in an aqueous suspension of biological bacterial cellulose. The designed nanocellulose-based colloidal LM ink is used for shape-deformable and electrically conductive LM-LCN soft robots that can be electro- and photo-thermally actuated. As proof-of-concept demonstrations, we present a light-fueled soft oscillator, an inchworm-inspired soft crawler and programmable robotic Shadow Play exhibiting multifunctional controllability. The strategy disclosed here could open up a new technological arena for advanced multifunctional soft materials with potential utility in bioinspired soft machines, integrated soft electronics, human-computer interaction and beyond. This journal isacceptedVersionPeer reviewe

    The Genetic Architecture of Depression in Individuals of East Asian Ancestry

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    Research on the Task Assignment Problem with Maximum Benefits in Volunteer Computing Platforms

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    As a type of distributed computing, volunteer computing (VC) has provided unlimited computing capacity at a low cost in recent decades. The architecture of most volunteer computing platforms (VCPs) is a master&ndash;worker model, which defines a master&ndash;slave relationship. Therefore, VCPs can be considered asymmetric multiprocessing systems (AMSs). As AMSs, VCPs are very promising for providing computing services for users. Users can submit tasks with deadline constraints to the VCPs. If the tasks are completed within their deadlines, VCPs will obtain the benefits. For this application scenario, this paper proposes a new task assignment problem with the maximum benefits in VCPs for the first time. To address the problem, we first proposed a list-based task assignment (LTA) strategy, and we proved that the LTA strategy could complete the task with a deadline constraint as soon as possible. Then, based on the LTA strategy, we proposed a maximum benefit scheduling (MBS) algorithm, which aimed at maximizing the benefits of VCPs. The MBS algorithm determined the acceptable tasks using a pruning strategy. Finally, the experiment results show that our proposed algorithm is more effective than current algorithms in the aspects of benefits, task acceptance rate and task completion rate

    Task Assignment Algorithm Based on Trust in Volunteer Computing Platforms

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    In volunteer computing (VC), the expected availability time and the actual availability time provided by volunteer nodes (VNs) are usually inconsistent. Scheduling tasks with precedence constraints in VC under this situation is a new challenge. In this paper, we propose two novel task assignment algorithms to minimize completion time (makespan) by a flexible task assignment. Firstly, this paper proposes a reliability model, which uses a simple fuzzy model to predict the time interval provided by a VN. This reliability model can reduce inconsistencies between the expected availability time and actual availability time. Secondly, based on the reliability model, this paper proposes an algorithm called EFTT (Earliest Finish Task based on Trust, EFTT), which can minimize makespan. However, EFTT may induce resource waste in task assignment. To make full use of computing resources and reduce task segmentation rate, an algorithm IEFTT (improved earliest finish task based on trust, IEFTT) is further proposed. Finally, experimental results verify the efficiency of the proposed algorithms

    Dynamic Task Scheduling Algorithm with Deadline Constraint in Heterogeneous Volunteer Computing Platforms

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    Volunteer computing (VC) is a distributed computing paradigm, which provides unlimited computing resources in the form of donated idle resources for many large-scale scientific computing applications. Task scheduling is one of the most challenging problems in VC. Although, dynamic scheduling problem with deadline constraint has been extensively studied in prior studies in the heterogeneous system, such as cloud computing and clusters, these algorithms can&#8217;t be fully applied to VC. This is because volunteer nodes can get offline whenever they want without taking any responsibility, which is different from other distributed computing. For this situation, this paper proposes a dynamic task scheduling algorithm for heterogeneous VC with deadline constraint, called deadline preference dispatch scheduling (DPDS). The DPDS algorithm selects tasks with the nearest deadline each time and assigns them to volunteer nodes (VN), which solves the dynamic task scheduling problem with deadline constraint. To make full use of resources and maximize the number of completed tasks before the deadline constraint, on the basis of the DPDS algorithm, improved dispatch constraint scheduling (IDCS) is further proposed. To verify our algorithms, we conducted experiments, and the results show that the proposed algorithms can effectively solve the dynamic task assignment problem with deadline constraint in VC

    Personalized epigenome remodeling under biochemical and psychological changes during long-term isolation environment

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    It has been reported that several aspects of human health could be disturbed during a long-term isolated environment (for instance, the Mars-500 mission), including psychiatric disorders, circadian disruption, temporal dynamics of gut microbiota, immune responses, and physical-activity-related neuromuscular performance. Nevertheless, the mechanisms underlying these disturbances and the interactions among different aspects of human adaptation to extreme environments remain to be elucidated. Epigenetic features, like DNA methylation, might be a linking mechanism that explains the involvement of environmental factors between the human genome and the outcome of health. We conducted an exploration of personalized longitudinal DNA methylation patterns of the peripheral whole blood cells, profiling six subjects across six sampling points in the Mars-500 mission. Specifically, we developed a Personalized Epigenetic-Phenotype Synchronization Analysis (PeSa) algorithm to explore glucose- and mood-state-synchronized DNA methylation sites, focusing on finding the dynamic associations between epigenetic patterns and phenotypes in each individual, and exploring the underling epigenetic connections between glucose and mood-state disturbance. Results showed that DMPs (differentially methylated-probes) were significantly enriched in pathways related to glucose metabolism (Type II diabetes mellitus pathway), mood state (Long-term depression) and circadian rhythm (Circadian entrainment pathway) during the mission. Furthermore, our data revealed individualized glucose-synchronized and mood-state-synchronized DNA methylation sites, and PTPRN2 was found to be associated with both glucose and mood state disturbances across all six subjects. Our findings suggest that personalized phenotype-synchronized epigenetic features could reflect the effects on the human body, including the disturbances of glucose and mood-states. The association analysis of DNA methylation and phenotypes, like the PeSa analysis, could provide new possibilities in understanding the intrinsic relationship between phenotypic changes of the human body adapting to long-term isolation environmental factors