Brain APOE expression quantitative trait loci-based association study identified one susceptibility locus for Alzheimer\u27s disease by interacting with APOE epsilon 4

AbstractSome studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479 normal controls from 12 cohorts of NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). 34 unrelated brain eQTLs for APOE were compiled from BRAINEAC and GTEx. We used multi-covariate logistic regression analysis to identify eQTLs interacted with APOE ε4. Adjusted for age and gender, substantia nigra eQTL rs438811 for APOE showed significantly strong interaction with APOE ε4 status (OR, 1.448; CI, 1.124–1.430; P-value = 7.94 × 10−6). APOE ε4-based sub-group analyses revealed that carrying one minor allele T of rs438811 can increase the opportunity of developing to AD by 26.75% in APOE ε4 carriers but not in non-carriers. We revealed substantia nigra eQTL rs438811 for APOE can interact with APOE ε4 and confers risk in APOE ε4 carriers only.</jats:p

A Bibliometric Analysis of Virtual Reality in Anatomy Teaching Between 1999 and 2022

Human anatomy is an important medical subject that includes abstract content and strong operability. The lack of specimens required for anatomical experimental teaching and unclear observation of fine structures of specimens lead to difficulties for students in learning. As a new technology in the field of computers, virtual reality (VR) has been widely used in the medical field and has great development potential and application value. Its use in the teaching of human anatomy has received increasing attention. This technology increases the sense of reality of medical students in learning and improves the learning effect, including initiative and enthusiasm of students. Publications were obtained from the Web of Science (WoS) Core Collection on April 30, 2022, with the following retrieval strategy: [(TS = VR) OR (TS = virtual reality)] AND (TS = anatomy) AND [(TS = education) OR (TS = train*) OR (TS = teach*) OR (TS = learn*) OR (TS = study*)] NOT TS = (surgery), and the time frame was from 1999 to 2022. Then, VOSviewer software, Excel and GraphPad Prism 9 were used to analyze the data. The keywords included cocitations, countries/territories, publication numbers, institutions, authors and journals of publications. A series of scientometric and visualized analyses were conducted, and a table for a detailed analysis of the application of VR in anatomy teaching was created. This paper mainly analyses the application status and progress of VR technology in anatomy teaching, which is shown to improve the anatomical learning effect of medical students. In conclusion, the application of VR technology in human anatomy has great potential

Bibliometric analysis of scientific papers on extracellular vesicles in kidney disease published between 1999 and 2022

Background: In recent years, there has been an increasing interest in using extracellular vesicles (EVs) as potential therapeutic agents or natural drug delivery systems in kidney-related diseases. However, a detailed and targeted report on the current condition of extracellular vesicle research in kidney-related diseases is lacking. Therefore, this prospective study was designed to investigate the use of bibliometric analysis to comprehensively overview the current state of research and frontier trends on extracellular vesicle research in kidney-related diseases using visualization tools.Methods: The Web of Science Core Collection (WoSCC) database was searched to identify publications related to extracellular vesicle research in kidney-related diseases since 1999. Citespace, Microsoft Excel 2019, VOSviewer software, the R Bibliometrix Package, and an online platform were used to analyze related research trends to stratify the publication data and collaborations.Results: From 1 January 1999 to 26 June 2022, a total of 1,122 EV-related articles and reviews were published, and 6,486 authors from 1,432 institutions in 63 countries or regions investigated the role of extracellular vesicles in kidney-related diseases. We found that the number of articles on extracellular vesicles in kidney-related diseases increased every year. Dozens of publications were from China and the United States. China had the most number of related publications, in which the Southeast University (China) was the most active institution in all EV-related fields. Liu Bi-cheng published the most papers on extracellular vesicles, while Clotilde Théry had the most number of co-citations. Most papers were published by The International Journal of Molecular Sciences, while Kidney International was the most co-cited journal for extracellular vesicles. We found that exosome-related keywords included exosome, exosm, expression, extracellular vesicle, microRNA, microvesicle, and liquid biopsy, while disease- and pathological-related keywords included biomarker, microRNA, apoptosis, mechanism, systemic lupus erythematosus, EGFR, acute kidney injury, and chronic kidney disease. Acute kidney disease (AKI), CKD, SLE, exosome, liquid biopsy, and extracellular vesicle were the hotspot in extracellular vesicle and kidney-related diseases research.Conclusion: The field of extracellular vesicles in kidney-related disease research is rapidly growing, and its domain is likely to expand in the next decade. The findings from this comprehensive analysis of extracellular vesicles in kidney-related disease research could help investigators to set new diagnostic, therapeutic, and prognostic ideas or methods in kidney-related diseases

The Gut Microbiota and Oxidative Stress in Autism Spectrum Disorders (ASD)

Autism spectrum disorders (ASDs) are a kind of neurodevelopmental disorder with rapidly increasing morbidity. In recent years, many studies have proposed a possible link between ASD and multiple environmental as well as genetic risk factors; nevertheless, recent studies have still failed to identify the specific pathogenesis. An analysis of the literature showed that oxidative stress and redox imbalance caused by high levels of reactive oxygen species (ROS) are thought to be integral parts of ASD pathophysiology. On the one hand, this review aims to elucidate the communications between oxidative stress, as a risk factor, and ASD. As such, there is also evidence to suggest that early assessment and treatment of antioxidant status are likely to result in improved long-term prognosis by disturbing oxidative stress in the brain to avoid additional irreversible brain damage. Accordingly, we will also discuss the possibility of novel therapies regarding oxidative stress as a target according to recent literature. On the other hand, this review suggests a definite relationship between ASD and an unbalanced gastrointestinal tract (GIT) microbiota (i.e., GIT dysbiosis). A variety of studies have concluded that the intestinal microbiota influences many aspects of human health, including metabolism, the immune and nervous systems, and the mucosal barrier. Additionally, the oxidative stress and GIT dysfunction in autistic children have both been reported to be related to mitochondrial dysfunction. What is the connection between them? Moreover, specific changes in the GIT microbiota are clearly observed in most autistic children, and the related mechanisms and the connection among ASD, the GIT microbiota, and oxidative stress are also discussed, providing a theory and molecular strategies for clinical practice as well as further studies

Effect of WC Nanoparticles on the Microstructure and Properties of WC-Bronze-Ni-Mn Based Diamond Composites

Metal matrix-impregnated diamond composites are widely used for fabricating diamond tools. In order to meet the actual engineering challenges, researchers have made many efforts to seek effective methods to enhance the performance of conventional metal matrices. In this work, tungsten carbide (WC) nanoparticles were introduced into WC-Bronze-Ni-Mn matrix with and without diamond grits for improving the performance of conventional impregnated diamond composites. The influence of WC nanoparticles on the microstructure, densification, hardness, bending strength and wear resistance of matrix and diamond composites were investigated. The results showed that the bending strength of matrix increased up to approximately 20% upon nano-WC addition, while densification and hardness fluctuate slightly. The grinding ratio of diamond composites increased significantly by about 100% due to nano-WC addition. The strengthening mechanism was proposed according to experimental results. The diamond composites with 2.8 wt% nano-WC addition exhibited the best overall properties, thus having potential to apply to further diamond tools

A microfluidics-based method for isolation and visualization of cells based on receptor-ligand interactions.

Receptor-ligand binding has been analyzed at the protein level using isothermal titration calorimetry and surface plasmon resonance and at the cellular level using interaction-associated downstream gene induction/suppression. However, no currently available technique can characterize this interaction directly through visualization. In addition, all available assays require a large pool of cells; no assay capable of analyzing receptor-ligand interactions at the single-cell level is publicly available. Here, we describe a new microfluidic chip-based technique for analyzing and visualizing these interactions at the single-cell level. First, a protein is immobilized on a glass slide and a low-flow-rate pump is used to isolate cells that express receptors that bind to the immobilized ligand. Specifically, we demonstrate the efficacy of this technique by immobilizing biotin-conjugated FGL2 on an avidin-coated slide chip and passing a mixture of GFP-labeled wild-type T cells and RFP-labeled FcγRIIB-knockout T cells through the chip. Using automated scanning and counting, we found a large number of GFP+ T cells with binding activity but significantly fewer RFP+ FcγRIIB-knockout T cells. We further isolated T cells expressing a membrane-anchored, tumor-targeted IL-12 based on the receptor's affinity to vimentin to confirm the versatility of our technique. This protocol allows researchers to isolate receptor-expressing cells in about 4 hours for further downstream processing

Elbow dislocation approach for complex elbow fractures: a cadaveric study

Abstract Background Approach need to be considered when surgeons dealt with complex elbow injuries and the choice of the approach is a challenge for surgeons due to the complex anatomy. On the basis of releasing the lateral collateral ligament, we modified the dislocation technique to pursue the superior exposure including not only the distal humeral surface but also the anterior facet of the coronoid process. Methods A total of 4 cadaver specimens and 8 elbows were included in the study. Each cadaver provided one elbow for either the elbow dislocation approach or the posterior olecranon approach. The exposed distal articular surface of humerus, humeral capitulum, humeral trochlea, anterior trochlea of distal humerus, posterior trochlea of distal humerus and the ulnar coronoid process surface were marked by image J software and calculated for a comparison for each surgical approach. Results The total distal humeral surface was exposed as a median of 98.2 (97.6, 99.6)% and 62.0 (58.3, 64.5)% for the elbow dislocation approach and the olecranon osteotomy approach (P < 0.001), the capitulum 100% and 32.4 (28.0, 39.2)% (P < 0.001), the trochlea 93.2(90.1, 96.9)% and 72.5 (65.2, 78.8)% (P < 0.001), the anterior trochlear articular surface 96.0(93.0, 97.4)% and 50.3 (43.6, 59.1)% (P < 0.001), the posterior trochlear articular surface 95.4 (93, 100)% and 100% (P = 0.76) and the articular surface of the coronoid process of ulna 71.3 (66.0, 74.2)% and 0% (P < 0.001). Conclusion For complex elbow fractures, the technique of elbow dislocation provides complete exposure of the distal humerus surface and a significant portion of the coronoid process surface, facilitating direct visualization for reduction and fixation. Level of evidence Anatomy Study; Cadaver Dissection

DualAfford: Learning Collaborative Visual Affordance for Dual-gripper Object Manipulation

It is essential yet challenging for future home-assistant robots to understand and manipulate diverse 3D objects in daily human environments. Towards building scalable systems that can perform diverse manipulation tasks over various 3D shapes, recent works have advocated and demonstrated promising results learning visual actionable affordance, which labels every point over the input 3D geometry with an action likelihood of accomplishing the downstream task (e.g., pushing or picking-up). However, these works only studied single-gripper manipulation tasks, yet many real-world tasks require two hands to achieve collaboratively. In this work, we propose a novel learning framework, DualAfford, to learn collaborative affordance for dual-gripper manipulation tasks. The core design of the approach is to reduce the quadratic problem for two grippers into two disentangled yet interconnected subtasks for efficient learning. Using the large-scale PartNet-Mobility and ShapeNet datasets, we set up four benchmark tasks for dual-gripper manipulation. Experiments prove the effectiveness and superiority of our method over three baselines. Additional results and videos can be found at https://hyperplane-lab.github.io/DualAfford

The Nrf-2/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases

Cardiovascular disease, which can lead to angina and shortness of breath, remains one of the most serious threats to human health. Owing to its imperceptible symptoms, it is difficult to determine the pathogenesis and treatment methods for cardiovascular disease. Nuclear factor erythropoietin-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) is a protein found in all cells of the human body. It is activated, transferred to the nucleus, and bound to DNA by antioxidant response elements (AREs). As a regulator of the antioxidant system, it upregulates the expression of HO-1 to reduce oxidative stress. Nrf2/HO-1 also has the ability to modulate calcium levels to prevent ferroptosis, pyroptosis, autophagy, programmed cell necrosis, alkaliptosis, and clockophagy. In view of the importance of Nrf2/HO-1 in the regulation of homeostasis, this review summarizes current research on the relationship between cardiovascular disease and Nrf2/HO-1. Normal cardiovascular diseases, such as viral myocarditis and myocardial ischemia-reperfusion injury, have been treated with Nrf2/HO-1. Rheumatic heart disease, cardiac tumors, arteriosclerosis, arrhythmia, hypertensive heart disease, and myocardial infarction have also been treated during experiments. Research has demonstrated the clinical application of Nrf2/HO-1 in pediatric cardiovascular disease; further clinical trials will help elucidate the potential of the Nrf2/HO-1 signaling axis