Friction plays a key role in the assessment of the safety and stability of mechanical systems (such as superconducting magnet quench explosion, aerospace vehicle bearing wear, etc.). Due to the ...closeness of the interfaces in engineering structures and the randomness of the contact surfaces, existing methods for measuring static friction force are unable to measure it at the contact interfaces of engineering structures under service conditions. In this paper, a new method for measuring the static friction force at the interface based on electrical signals is proposed. This method enables the measurement of the static friction force at interfaces of complex engineering structures under service conditions solely through electrical signals. The results indicate that the contact resistance gradually decreases with the increase in tangential load during the static friction stage until a monotonic behavior of macroscopic sliding occurs. The evolution of contact resistance is linked to the evolution of the real contact area, and this monotonic behavior can be explained as the deformation form of contact points. The accuracy of the proposed electrical measurement method is verified by comparison with experimental results (with an error of less than 9%). The indirect measurement method of friction force proposed in this paper can effectively measure the static friction force at the interfaces of engineering structures under service conditions, and it is expected to be applied to the detection of friction performance at engineering structure interfaces in extreme service environments.
This prospective clinical study was to compare the effect of panretinal photocoagulation (PRP) associated with intravitreal conbercept injections versus PRP alone in the treatment of proliferative ...diabetic retinopathy (PDR). For each of 15 patients included, one eye was randomly assigned to receive treatment with PRP, and the other eye received conbercept combined PRP. Ophthalmic examinations, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were performed at baseline and at each monthly visit until 6 months. Fluorescein angiography (FA) was acquired at baseline, 3 months and 6 months. Between group and within group analysis was done by using generalized estimating equations (GEE). The combination group had a significant decrease of neovascularization (NV) leakage area than the PRP group at month 3 and month 6 after treatment, and a better best-corrected visual acuity (BCVA) during the first three months. Within-group analysis indicated a significant decrease in NV leakage at month 3 and month 6 in both groups, and a significant increase in BCVA at 1 month in the combination group. In summary, the combination of intravitreal injection of conbercept and PRP can significantly reduce the NV of PDR patients and achieve better BCVA during the drug's lifespan compared with PRP alone.
The development of Alzheimer's dementia (AD) accompanies both central and peripheral metabolic disturbance, but the metabolic basis underlying AD and metabolic markers predictive of AD risk remain to ...be determined. It is also unclear whether the metabolic changes in the peripheral blood and brain are overlapping in relation to AD. The present study addresses these questions by targeted metabolomics in both antemortem blood and postmortem brain samples in 2 community-based longitudinal cohorts of aging and dementia. We found that higher serum levels of 3 acylcarnitines, including decanoylcarnitine (C10), pimelylcarnitine (C7-DC), and tetradecadienylcarnitine (C14:2), significantly predict a lower risk of incident AD (composite hazard ratio = 0.368, 95% CI 0.207, 0.653) after an average of 4.5-year follow-up, independent of age, sex, and education. In addition, baseline serum levels of ten glycerophospholipids, one amino acid, and 5 acylcarnitines predict the longitudinal change in cognitive functions. Moreover, 28 brain metabolites were associated with AD phenotypes. Of the putative metabolites identified in the serum and brain, 4 metabolites (3 glycerophospholipids PC aa C30:0, PC ae C34:0, PC ae C36:1 and 1 acylcarnitine C14:2) were present in both the postmortem brain and antemortem blood, but only one metabolite (C14:2) was associated with AD in the same direction (i.e., protective). Partial correlation and network analyses suggest a potential tissue-specific regulation of metabolism, although other alternatives exist. Together, we identified significant associations of both central and peripheral metabolites with AD phenotypes, but there seems to be little overlap between the 2 tissues.
•Blood metabolites increase AD risk prediction beyond traditional clinical factors.•Metabolic disturbance could be implicated in AD pathology.•We found little overlap between peripheral and central metabolisms in relation to AD.•Metabolomics analysis of the blood and brain of same individuals.
To prioritize genes that were pleiotropically or potentially causally associated with central corneal thickness (CCT).
We applied the summary data-based Mendelian randomization (SMR) method ...integrating summarized data of genome-wide association study (GWAS) on CCT and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with CCT. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analyses were done for participants of European and East Asian ancestries, separately.
We identified multiple genes showing pleiotropic association with CCT in the participants of European ancestry. CLIC3 (ILMN_1796423; P
= 4.15 × 10
), PTGDS (ILMN_1664464; P
= 6.88 × 10
) and C9orf142 (ILMN_1761138; P
= 8.09 × 10
) were the top three genes using the CAGE eQTL data, and RP11-458F8.4 (ENSG00000273142.1; P
= 5.89 × 10
), LCNL1 (ENSG00000214402.6; P
= 5.67 × 10
), and PTGDS (ENSG00000107317.7; P
= 1.92 × 10
) were the top three genes using the GTEx eQTL data. No genes showed significantly pleiotropic association with CCT in the participants of East Asian ancestry after correction for multiple testing.
We identified several genes pleiotropically associated with CCT, some of which represented novel genes influencing CCT. Our findings provided important leads to a better understanding of the genetic factors influencing CCT, and revealed potential therapeutic targets for the treatment of primary open-angle glaucoma and keratoconus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide association studies have identified many loci associated with Alzheimer's dementia. However, these variants only explain part of the heritability of Alzheimer's disease (AD). As genetic ...epistasis can be a major contributor to the “missing heritability” of AD, we conducted genome-wide epistasis screening for AD pathologies in 2 independent cohorts. First, we performed a genome-wide epistasis study of AD-related brain pathologies (Nmax = 1318) in ROS/MAP. Candidate interactions were validated using cerebrospinal fluid biomarkers of AD in ADNI (Nmax = 1128). Further functional analysis tested the association of candidate interactions with neuroimaging phenotypes. For tau and amyloid-β pathology, we identified 2803 and 464 candidate SNP-SNP interactions, respectively. Associations of candidate SNP-SNP interactions with brain volume and white matter changes from neuroimages provides additional insights into their molecular functions. Transcriptional analysis supported possible gene-gene interactions identified by statistical screening through their co-expression in the brain. In summary, we outlined an exhaustive epistasis analysis to identify novel genetic interactions with potential roles in AD pathologies. We further delved into the functional relevance of candidate interactions by association with neuroimaging phenotypes and analysis of co-expression between corresponding gene pairs.
•Genetic interactions help explain the “missing heritability” in Alzheimer's disease.•We conducted a genome-wide epistasis analysis for Alzheimer's disease pathologies.•The epistasis signals were replicated in independent data.•Transcriptome analysis supported the interactions (such as INPP4B/RBFOX1 interaction).•Association with neuroimages provides insights into molecular functions of interactions.
Abstract
The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune ...escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.
Previous genome-wide association studies (GWAS) have identified potential genetic variants involved in the risk of Alzheimer's dementia, but their underlying biological interpretation remains largely ...unclear. In addition, the effects of DNA methylation and gene expression on Alzheimer's dementia are not well understood. A network summary data-based Mendelian randomization (SMR) analysis was performed integrating cis- DNA methylation quantitative trait loci (mQTL) /cis- gene expression QTL (eQTL) data in the brain and blood, as well as GWAS summarized data for Alzheimer's dementia to evaluate the pleiotropic associations of DNA methylation and gene expression with Alzheimer's dementia and to explore the complex mechanisms underpinning Alzheimer's dementia. After correction for multiple testing (false discovery rate FDR P < 0.05) and filtering using the heterogeneity in dependent instruments (HEIDI) test (P
HEIDI
>0.01), we identified dozens of DNA methylation sites and genes showing pleiotropic associations with Alzheimer's dementia. We found 22 and 16 potentially causal pathways of Alzheimer's dementia (i.e., SNP→DNA methylation→Gene expression→Alzheimer's dementia) in the brain and blood, respectively. Approximately two-thirds of the identified DNA methylation sites had an influence on gene expression and the expression of almost all the identified genes was regulated by DNA methylation. Our network SMR analysis provided evidence supporting the pleiotropic association of some novel DNA methylation sites and genes with Alzheimer's dementia and revealed possible causal pathways underlying the pathogenesis of Alzheimer's dementia. Our findings shed light on the role of DNA methylation in gene expression and in the development of Alzheimer's dementia.
Previous genome-wide association studies (GWAS) have identified potential genetic variants associated with the risk of major depressive disorder (MDD), but the underlying biological interpretation ...remains largely unknown. We aimed to prioritize genes that were pleiotropically or potentially causally associated with MDD. We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and gene expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta). We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleiotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in the immune response. Our SMR analysis indicated that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provided important leads to a better understanding of the mechanism of MDD and revealed potential therapeutic targets for the prevention and effective treatment of MDD.
In this study, α-chitin nanofibers (CNFs)–poly(vinyl alcohol) (PVA) composite films were fabricated to evaluate the compatibility and reinforcement effect of CNFs to PVA. CNFs were disintegrated by ...one-pass grinding and 40-min ultrasonication. The diameter of most of CNFs ranged from 30nm to 50nm. The CNFs–PVA composite films were made by immersing CNFs sheet into PVA solution. FTIR and XRD analysis revealed that there are strong interaction and good compatibility between CNFs and PVA molecular. In comparison with the neat PVA film, the light transmittance of the composite film slightly decreased from 92% to 86%. The coefficient of thermal expansion dramatically decreased from 123.62ppmK−1 to 25.09ppmK−1. The tensile strength and Young’s modulus were high to 127MPa and 5.70GPa, which were about 100% and 140% larger than those of the PVA film. The elongation at break point of the composite film decreased from 20.70% to 4.40%.
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