Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer’s Disease Development

Alzheimer’s disease (AD) is the most common cause of dementia. Although genome-wide association study (GWAS) have reported hundreds of single-nucleotide polymorphisms (SNPs) and genes linked to AD, the mechanisms about how these SNPs modulate the development of AD remain largely unknown. In this study, we performed GWAS for three traits in cerebrospinal fluid (CSF) and one clinical trait in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Our analysis identified five most significant AD related SNPs (FDR < 0.05) within or proximal to APOE, APOC1, and TOMM40. One of the SNPs was co-inherited with APOE allele 4, which is the most important genetic risk factor for AD. Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptor-related 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). The altered regulation of PVRL2 may increase the susceptibility AD patients to HSV and other virus infections of the brain. Our work suggests that AD is a type of immune disorder driven by viral or microbial infections of the brain during aging

Runt-related transcription factor 3 promoter hypermethylation and gastric cancer risk: A meta-analysis

The aim of this study was to investigate the correlation between runt-related transcription factor 3 (RUNX3) gene promoter hypermethylation and gastric cancer risk by meta-analysis

Synthesis and electrochemical performance of porous Li2FeSiO4/C cathode material for long-life lithium-ion batteries

Porous Li2FeSiO4/C composite is synthesized using a facile one-step technique. The Li2FeSiO4/C composite is characterized by a large amount of particles with the size of similar to 5 mu m. These particles are composed of a large number of smaller crystal grains with the size of similar to 100 nm, which are combined by many irregular pores. This structure can not only offer channels for infiltration of liquid electrolyte, but also avoid aggregation of nanoparticles during the synthesis itself and/or during electrochemical cycling. The electrochemical test result indicates that although the Li2FeSiO4/C cathode shows a lower initial discharge capacity of 134 mAh g(-1), it improves to 155 mAh g(-1) after 190 electrochemical cycles. (C) 2009 Elsevier B.V. All rights reserved.National Natural Science Foundation of China [20903016]; Cultivation Fund of the Key Scientific and Technical Innovation Project, Ministry of Education of China [708084]; Major State Basic Research Development "973" Program of China [2009CB220102

Clamping Fatigue Properties of Shrink-Fit Holder

In order to explore the clamping fatigue properties of shrink-fit holders, ANSYS software was used in this study to analyze the thermal and contact stresses during the clamping process of the shrink-fit holder, and the fatigue analysis was performed by selecting the dangerous areas based on the two stresses. A numerical control shrink-fit holder clamping fatigue test device was manufactured, and the automatic clamping of the shrink-fit holder was executed in this study. After 500 clamping repetitions, a milling test was carried out on the shrink-fit bracket. By collecting the vibration signal of the workpiece during processing and measuring the change in the surface roughness of the workpiece, and then analyzing the change in the machining performance of the shrink-fit holder under different clamping times, we were able to compare and verify the accuracy of the finite element fatigue analysis

Thermo-mechanical behavior assessment of smart wire connected and busbarPV modules during production, transportation, and subsequent field loading stages

Thermo-mechanical loads induce stresses in photovoltaic (PV) modules, leading to crack formation. In this context, the understanding of module’s thermo-mechanical behavior is important. To investigate the thermo-mechanical behavior of smart wire connected technology (SWCT) and busbar PV modules throughout their entire life, the present study is conducted that probes the stress distribution and deformation during production, transportation, and subsequent mechanical and thermal loading stages in a consecutive step-by-step manner using finite element modelling approach. Pre-stresses and non-linearities are considered in simulation models. Stresses and displacements experienced by different parts/layers are examined, and crack sensitive regions are identified. In addition, the SWCT and busbar modules are compared, and it is found that SWCT interconnection is relatively a less stress inducing process and less susceptible to thermal and dynamic affects. During production stage, stresses of 39.3 MPa and 40.4 MPa are generated in SWCT cells and copper wires respectively; while, stresses of 60 MPa and 87 MPa are generated in busbar cells and busbar respectively. Similarly, lower stresses are induced in SWCT PV modules during subsequent stages. The comparison results show advantages of SWCT module in terms of mechanical stability which can lead to improve the performance and reliability of PV modules

Nanomolar Hg²⁺ Detection Using β‑Lactoglobulin-Stabilized Fluorescent Gold Nanoclusters in Beverage and Biological Media

Owing to diverse functionalities and metal binding abilities, proteins have been proven to be promising ligands in the synthesis of gold nanoclusters (Au NCs). In this work, we explored β-lactoglobulin (β-Lg), a protein byproduct generated during cheese processing, as a biotemplate for fabrication of Au NCs by a facile and green method for the first time. The as-prepared Au NCs are water soluble and highly fluorescent and exhibit high sensitivity and selectivity for Hg²⁺ detection in aqueous solution. Interestingly, we found that the fluorescence of these Au NCs is stable either in a variety of complex matrixes or over a broad pH range (5.0–13.0) and therefore can be explored as a cell and animal imaging agent. More importantly, we demonstrated that the β-lactoglobulin-stabilized Au NCs (β-Lg–Au NCs) could serve as a sensor for the detection and quantification of Hg²⁺ in beverages, urine, and serum with high sensitivity

Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials

PurposeApproximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention.MethodsThe PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR).ResultsSeven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = −2.40, 95% confidence interval (CI): −3.38 to −1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001].ConclusionsTicagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes