Relationship of body mass index and visceral fat area combination with arterial stiffness and cardiovascular risk in cardiovascular disease-free people: NHANES (2011–2018)

Background: Obesity and arterial stiffness are strongly associated with car diovascular disease; however, their relationship remains controversial. Methods: Body mass index was measured using anthropometric evaluation, and visceral fat area was calculated using an absorptiometry scan. Results: The data of 5309 participants were collected from NHANES (National Health and Nutrition Examination Survey) (2011–2018). Based on the normal-weight normal visceral fat group that was considered as a reference, ePWV increased in all other groups, with the obese grade 2 visceral obesity group increasing the most by 26.35 cm/s (95% CI: 13.52, 39.18, P < 0.001), followed by normal-weight visceral obesity group 24.43 cm/s (95% CI: 1.88, 46.98, P = 0.035), which was even higher than obese grade 1 visceral obesity (β: 21.16, 95% CI: 9.24, 33.07, P = 0.001), obese grade 2 normal visceral fat group (β: 13.8; 95% CI: 0.10, 27.5, P = 0.048) and overweight visceral obesity group (β: 10.23; 95% CI: 1.89, 18.57, P = 0.018). For the 10-year cardiovascular risk, the obese grade 2 visceral obesity group had a 9.56-fold increase in compared with the control (OR: 10.56, 95% CI: 4.06, 27.51, P < 0.0001). Normal-weight visceral obesity, obese grade 1 visceral obesity, and overweight visceral obesity groups increased by 8.03-fold (OR: 9.03, 95% CI: 2.66, 30.69; P < 0.001), 7.91-fold (OR: 8.91, 95% CI: 3.82, 20.79, P < 0.001), and 7.28-fold (OR: 8.28, 95% CI: 3.19, 21.46, P < 0.001). The risk was lower in the normal visceral fat group. Except for the obese grade 2 normal visceral fat group, there was no significant difference in other groups. Conclusions: Normal-weight visceral obesity was associated with higher arterial stiffness and 10-year cardiovascular risk

Exploration of bivalent ligands targeting putative mu opioid receptor and chemokine receptor CCR5 dimerization

Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer. In an attempt to understand this putative interaction and its relevance to neuroAIDS, we designed and synthesized a series of bivalent ligands targeting the putative CCR5-MOR heterodimer. To understand how these bivalent ligands may interact with the heterodimer, biological studies including calcium mobilization inhibition, binding affinity, HIV-1 invasion, and cell fusion assays were applied. In particular, HIV-1 infection assays using human peripheral blood mononuclear cells, macrophages, and astrocytes revealed a notable synergy in activity for one particular bivalent ligand. Further, a molecular model of the putative CCR5-MOR heterodimer was constructed, docked with the bivalent ligand, and molecular dynamics simulations of the complex was performed in a membrane-water system to help understand the biological observation

Comprehensive Network Analysis Reveals Alternative Splicing-Related lncRNAs in Hepatocellular Carcinoma

© Copyright © 2020 Wang, Wang, Bhat, Chen, Xu, Mo, Yi and Zhou. It is increasingly appreciated that long non-coding RNAs (lncRNAs) associated with alternative splicing (AS) could be involved in aggressive hepatocellular carcinoma. Although many recent studies show the alteration of RNA alternative splicing by deregulated lncRNAs in cancer, the extent to which and how lncRNAs impact alternative splicing at the genome scale remains largely elusive. We analyzed RNA-seq data obtained from 369 hepatocellular carcinomas (HCCs) and 160 normal liver tissues, quantified 198,619 isoform transcripts, and identified a total of 1,375 significant AS events in liver cancer. In order to predict novel AS-associated lncRNAs, we performed an integration of co-expression, protein-protein interaction (PPI) and epigenetic interaction networks that links lncRNA modulators (such as splicing factors, transcript factors, and miRNAs) along with their targeted AS genes in HCC. We developed a random walk-based multi-graphic (RWMG) model algorithm that prioritizes functional lncRNAs with their associated AS targets to computationally model the heterogeneous networks in HCC. RWMG shows a good performance evaluated by the ROC curve based on cross-validation and bootstrapping strategies. As a conclusion, our robust network-based framework has derived 31 AS-related lncRNAs that not only validates known cancer-associated cases MALAT1 and HOXA11-AS, but also reveals new players such as DNM1P35 and DLX6-AS1with potential functional implications. Survival analysis further provides insights into the clinical significance of identified lncRNAs

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants

Studies have reported that &gt;91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective: To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology: We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results: We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C&gt;A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion: We found that PAX9 variants commonly lead to loss of the second molars

Observation of two-dimensional yttrium oxide nanoparticles in mealworm beetles ( Tenebrio molitor )

Nanomaterials are being used in medicine, manufacturing and consumer products, but their effects on organisms and the environment are not well understood because of the difficulty in detecting them. Here dual-energy X-rayK-edge subtraction was used to track two-dimensional yttrium oxide nanoparticles (which can be found in such household objects as color televisions) in adult mealworms (Tenebrio molitor). The insects ingested nanoparticle-infused feed for different time periods, up to 24 h, and the nanoparticles could then be identified at several locations in the insects' head, thorax and abdomen, mostly within the digestive tract. In time, all particles were excreted.</jats:p

Observation of yttrium oxide nanoparticles in cabbage (Brassica oleracea) through dual energy K-edge subtraction imaging

BACKGROUND: The potential transfer of engineered nanoparticles (ENPs) from plants into the food chain has raised widespread concerns. In order to investigate the effects of ENPs on plants, young cabbage plants (Brassica oleracea) were exposed to a hydroponic system containing yttrium oxide (yttria) ENPs. The objective of this study was to reveal the impacts of NPs on plants by using K-edge subtraction imaging technique. RESULTS: Using synchrotron dual-energy X-ray micro-tomography with K-edge subtraction technique, we studied the uptake, accumulation, distribution and concentration mapping of yttria ENPs in cabbage plants. It was found that yttria ENPs were uptaken by the cabbage roots but did not effectively transferred and mobilized through the cabbage stem and leaves. This could be due to the accumulation of yttria ENPs blocked at primary-lateral-root junction. Instead, non-yttria minerals were found in the xylem vessels of roots and stem. CONCLUSIONS: Synchrotron dual-energy X-ray micro-tomography is an effective method to observe yttria NPs inside the cabbage plants in both whole body and microscale level. Furthermore, the blockage of a plant’s roots by nanoparticles is likely the first and potentially fatal environmental effect of such type of nanoparticles

The performance of large-pitch AC-LGAD with different N+ dose

AC-Coupled LGAD (AC-LGAD) is a new 4D detector developed based on the Low Gain Avalanche Diode (LGAD) technology, which can accurately measure the time and spatial information of particles. Institute of High Energy Physics (IHEP) designed a large-size AC-LGAD with a pitch of 2000 {\mu}m and AC pad of 1000 {\mu}m, and explored the effect of N+ layer dose on the spatial resolution and time resolution. The spatial resolution varied from 32.7 {\mu}m to 15.1 {\mu}m depending on N+ dose. The time resolution does not change significantly at different N+ doses, which is about 15-17 ps. AC-LGAD with a low N+ dose has a large attenuation factor and better spatial resolution. Large signal attenuation factor and low noise level are beneficial to improve the spatial resolution of the AC-LGAD sensor

Characterization of the response of IHEP-IME LGAD with shallow carbon to Gamma Irradiation

Low Gain Avalanche Detectors (LGAD), as part of High-Granularity Timing Detector (HGTD), is crucial to reducing pileup in the upgrading to HL-LHC. Many studies have been done on the bulk damages of the LGAD. However, there's no study about the surface radiation hardness of the LGAD sensors with carbon implanted. The IHEP-IME LGAD version 3 with the shallow carbon and different interpad separations were irradiated up to 2 MGy by gamma irradiation. The performance of the IHEP-IME LGAD version 3 before and after irradiation had been tested, such as the leakage current, break-down voltage, capacitance, V$_{gl}$, and inter-pad resistance. The results showed that apart from minor fluctuations in some samples, no significant changes concerning inter-pad separation were observed before and after irradiation. Leakage current and break-down voltage increase after irradiation, which is considered due to surface passivation; the overall inter-pad resistance are larger than $10^9\ \Omega$before and after irradiation; capacitance is found to be less than 4.5 pF with a slight drop in V$_{gl}$ after irradiation. All parameters meet the requirements of HGTD, and the results indicated that IHEP-IME LGAD v3 has excellent anti-irradiation performance

Characterisation of Spatial and Timing Resolution of IHEP AC-LGAD Strip

AC-coupled LGAD(AC-LGAD) Strip is a new design of LGAD that allows high-precision detection of particle spatiotemporal information whereas reducing the density of readout electronics. For AC-LGAD Strips, there is limited research on the impact of different strip pitches on the spatiotemporal detection performance at the small amount of injected charge. The Institute of High Energy Physics has designed an AC-LGAD Strip prototype with pitches of 150 $\mu m$, 200 $\mu m$, and 250 $\mu m$. The spatial and timing resolutions of the prototype are studied through the laser Transient Current Technique (TCT) scan with different amounts of injected charge. The results show that both the spatial and timing resolution improves as the strip pitch decreases. Increases in both temporal and spatial resolutions as the amount of charge injected increases are observed. The spatial and timing resolution is better than 60 ps and 40 $\mu m$ at 1 Minimum Ionizing Particle (MIP), and better than 10 ps and 5 $\mu m$ at 40 MIPs. Increasing Signal-to-Noise Ratio (SNR) is the key to improving spatial and temporal resolution, whereas increasing the signal attenuation rate by reducing the gap between adjacent electrodes also helps to improve spatial resolution. The enhancements of spatial and timing resolutions by both SNR and signal attenuation rate decrease with increasing amount of MIP. This study can help design and optimize the AC-LGAD Strip detectors and readout electronics