In this work, molecular dynamics simulations are performed to investigate the nanoscale wear behavior of SiC particle-reinforced aluminum matrix composites (SiC/Al NCs) through nanoscratching using a ...spherical diamond indenter. A series of simulations are conducted to explore the effects of scratching depth, scratching speed, temperature, indenter size, and particle size during the nanoscratching process. We find the dislocation strengthening in the nanoscratching of SiC/Al NCs. It is also found that the frictional force and normal force increase with the increase of scratching depth, indenter size, and nanoparticle size. Moreover, the friction coefficient increases with the scratching depth. However, the friction coefficient declines with the increase of indenter size and nanoparticle size. Furthermore, for a larger scratching speed, the frictional force becomes smaller, while the normal force becomes larger, which is mainly determined by the competition between strain rate hardening and thermal softening. We also find that both the frictional force and normal force become smaller for a higher temperature resulting from thermal softening effect. The insights into the nanoscale wear properties of SiC/Al NCs lay a foundation for the wide applications of SiC/Al NCs.
Graphical Abstract
Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human ...disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC ...are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets. Meanwhile, the summary receiver operating characteristic (sROC) curve analysis result showed that DEPDC1 had a high diagnostic value in NSCLC (AUC = 0.96, 95% CI: 0.94-0.98; diagnostic odds ratio = 99.08, 95%CI: 31.91-307.65; sensitivity = 0.89, 95%CI: 0.81-0.94; specificity = 0.92, 95%CI: 0.86-0.96; positive predictive value = 0.94, 95%CI: 0.89-0.98; negative predictive value = 0.78, 95%CI: 0.67-0.90; positive likelihood ratio = 11.77, 95%CI: 6.11-22.68; and negative likelihood ratio = 0.12, 95%CI: 0.06-0.22). Subsequently, quantitative real-time PCR (qRT-PCR) and western blotting indicated that DEPDC1 was high expressed in NSCLC cells. According to the in vitro MTS and apoptotic assays, downregulated DEPDC1 expression targeting P53 signaling pathway inhibited the proliferation of NSCLC cells while promoting apoptosis of NSCLC cells. Moreover, DEPDC1 was significantly correlated with immune cell infiltrating levels in NSCLC based on TCGA data, which were primarily associated with T cells CD4 memory activated, macrophages M1, B cells memory, mast cells resting, T cells regulatory, monocytes, and T cells CD4 memory resting. Compared with the group with high expression of DEPDC1, the group with low expression level had higher scores for immune checkpoint inhibitors (ICIs) treatment. GSEA confirmed that DEPDC1 was involved in gene expression and tumor-related signaling pathways. Finally, DEPDC1 and its associated immune-related genes were shown to be enriched in 'receptor ligand activity', 'external side of plasma membrane', 'regulation of innate immune response', and 'Epstein-Barr virus infection' pathways. The present study demonstrates that DEPDC1 may contribute to NSCLC tumorigenesis and can be applied as the biomarker for diagnosis and immunology.
The protocol for delayed-interval delivery of the second twin in twin pregnancies has not been standardized. Cervical cerclage is often performed, but its use is debated. To conduct a scoping review ...on cervical cerclage for prolonging the intertwin delivery interval and improving second twin survival and maternal outcomes after preterm delivery or spontaneous abortion of the first twin in twin pregnancies.
Seven Chinese and English language databases were searched from inception to March 1, 2023, including PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP Chinese Science Journal Database, and Sinomed. Relevant observational studies that assessed the effectiveness of the use of cervical cerclage in delayed-interval delivery of twins were screened and selected, and raw data were extracted, and descriptive statistics and chi-square analysis were performed.
A total of 102 articles were retrieved. After screening and exclusion of duplicate and irrelevant articles, 22 articles meeting the inclusion criteria were obtained. Studies in which cerclage was performed reported longer intertwin delivery intervals than those that did not perform cerclage, and the difference was statistically significant. The cerclage group also tended to have lower rates of chorioamnionitis and maternal complications, but the difference between the two groups was not statistically significant.
After excluding patients with contraindications, emergency cervical cerclage can be considered in cases of spontaneous abortion of the first twin in twin pregnancies to prolong the gestation and improve the prognosis of the remaining fetus until it becomes viable and increases its birth weight.
Lung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the ...survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD.
We obtained miRNA expression profiles and corresponding clinical information for 372 LUAD patients from The Cancer Genome Atlas (TCGA), and identified the most significantly altered miRNAs between tumor and normal samples. Using survival analysis and supervised principal components method, we identified an eight-miRNA signature for the prediction of overall survival (OS) of LUAD patients. The relationship between OS and the identified miRNA signature was self-validated in the TCGA cohort (randomly classified into two subgroups: n = 186 for the training set and n = 186 for the testing set). Survival receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. The biological relevance of putative miRNA targets was also analyzed using bioinformatics.
Sixteen of the 111 most significantly altered miRNAs were associated with OS across different clinical subclasses of the TCGA-derived LUAD cohort. A linear prognostic model of eight miRNAs (miR-31, miR-196b, miR-766, miR-519a-1, miR-375, miR-187, miR-331 and miR-101-1) was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group exhibited poor OS compared with patients in the low-risk group (hazard ratio HR = 1.99, P <0.001). The eight-miRNA signature is an independent prognostic marker of OS of LUAD patients and demonstrates good performance for predicting 5-year OS (Area Under the respective ROC Curves AUC = 0.626, P = 0.003), especially for non-smokers (AUC = 0.686, P = 0.023).
We identified an eight-miRNA signature that is prognostic of LUAD. The miRNA signature, if validated in other prospective studies, may have important implications in clinical practice, in particular identifying a subgroup of patients with LUAD who are at high risk of mortality.
Lung cancer is the major cause of cancer death globally, it is often diagnosed at an advanced stage and has one of the lowest survival rates of any type of cancer. The common interest in the field of ...lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence to suggest that microRNAs play important and complex roles in lung cancer.
A meta-analysis was conducted to review the published microRNA expression profiling studies that compared the microRNAs expression profiles in lung cancer tissues with those in normal lung tissues. A vote-counting strategy that considers the total number of studies reporting its differential expression, the total number of tissue samples used in the studies and the average fold change was employed.
A total of 184 differentially expressed microRNAs were reported in the fourteen microRNA expression profiling studies that compared lung cancer tissues with normal tissues, with 61 microRNAs were reported in at least two studies. In the panel of consistently reported up-regulated microRNAs, miR-210 was reported in nine studies and miR-21 was reported in seven studies. In the consistently reported down-regulated microRNAs, miR-126 was reported in ten studies and miR-30a was reported in eight studies. Four up-regulated microRNAs (miR-210, miR-21, miR-31 and miR-182) and two down-regulated mcroiRNAs (miR-126 and miR-145) were consistently reported both in squamous carcinoma and adenocarcinoma-based subgroup analysis, with the other 14 microRNAs solely reported in one or the other subset.
In conclusion, the top two most consistently reported up-regulated microRNAs were miR-210 and miR-21. The results of this meta-analysis of human lung cancer microRNA expression profiling studies might provide some clues of the potential biomarkers in lung cancer. Further mechanistic and external validation studies are needed for their clinical significance and role in the development of lung cancer.
Despite strong evidence that human genetic variants affect the expression of many key transcription factors involved in autoimmune diseases, establishing biological links between non-coding risk ...variants and the gene targets they regulate remains a considerable challenge. Here, we combine genetic, epigenomic, and CRISPR activation approaches to screen for functional variants that regulate IRF8 expression. We demonstrate that the locus containing rs2280381 is a cell-type-specific enhancer for IRF8 that spatially interacts with the IRF8 promoter. Further, rs2280381 mediates IRF8 expression through enhancer RNA AC092723.1, which recruits TET1 to the IRF8 promoter regulating IRF8 expression by affecting methylation levels. The alleles of rs2280381 modulate PU.1 binding and chromatin state to regulate AC092723.1 and IRF8 expression differentially. Our work illustrates an integrative strategy to define functional genetic variants that regulate the expression of critical genes in autoimmune diseases and decipher the mechanisms underlying the dysregulation of IRF8 expression mediated by lupus risk variants.
The convenience of online learning helps physical education teachers overcome geographic barriers and promotes safe, accessible, high-quality education. This three-stage study developed an evaluation ...index system for online learning literacy of physical education (PE) teachers (OLLPET).
Using two rounds of the Delphi method and one round of the Expert ranking method, consult with 15 PE experts from universities, primary and secondary schools, and teaching-research staff to draw up, revise, and finalize an evaluation index system for OLLPET.
Our OLLPET evaluation index system includes three first-level indicators, seven second-level indicators and 30 third-level indicators. The first-level indicators includes online learning values (OLV), online learning essential character (OLEC), and online learning key competencies (OLKC)-with equal weighting given to OLV (0.367) and OLKC (0.367) and slightly less given to OLEC (0.267).
The OLLPET evaluation index system is a theoretical yet practical tool that governments, schools, and teachers can use to evaluate PE teachers' online learning literacy to improve their learning capacity in a targeted manner.
In the present study, molecular dynamics (MD) simulations are applied to investigate the polishing process of cubic silicon carbide (3C-SiC) with a rotating abrasive. The influence of abrasive ...rotational speed and rotation axis orientation on the friction characteristics and deformation behaviors of 3C-SiC is studied. The results show that as the rotational speed increases, the normal force first increases until it reaches its maximum at 25 rad/ns and then decreases. The evolution of transverse force with the rotational speed is more complicated and the smallest transverse force and friction coefficient are obtained at the rotational speed of 50 rad/ns. Besides, the transverse force increases while the normal force decreases with the rotation angle when the angular velocity vector of the rotational abrasive is parallel to the substrate surface. The case when the rotational speed is 25 rad/ns and the rotation angle is 0 is a significant critical situation. At the critical situation, we observe the lowest material removal rate, the deepest subsurface damage layer, the biggest high stress region and the smallest high temperature region for all rotational speeds and rotation axis orientations. Moreover, in the simulations, phase transformation (mainly amorphization) induced by high pressure is more pronounced than that by thermal effect. The results gained can shed light on the atomic-scale material removal and deformation mechanisms of 3C-SiC during polishing process.
Graphic Abstract
Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is ...derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.
PDF
