Background
Diabetic retinopathy (DR) is a common complication of diabetes mellitus that poses a threat to adults. MicroRNAs (miRNAs) play a key role in DR progression. However, the role and mechanism ...of miR‐192‐5p in DR remain unclear. We aimed to investigate the effect of miR‐192‐5p on cell proliferation, migration and angiogenesis in DR.
Methods
Expression of miR‐192‐5p, ELAV‐like RNA binding protein 1 (ELAVL1) and phosphoinositide 3‐kinase delta (PI3Kδ) in human retinal fibrovascular membrane (FVM) samples and human retinal microvascular endothelial cells (HRMECs) was assessed using RT‐qPCR. ELAVL1 and PI3Kδ protein levels were evaluated by Western blot. RIP and dual luciferase reporter assays were performed to confirm the miR‐192‐5p/ELAVL1/PI3Kδ regulatory networks. Cell proliferation, migration and angiogenesis were assessed by CCK8, transwell and tube formation assays.
Results
MiR‐192‐5p was decreased in FVM samples from DR patients and high glucose (HG)‐treated HRMECs. Functionally, overexpressed miR‐192‐5p inhibited cell proliferation, migration and angiogenesis in HG‐treated HRMECs. Mechanically, miR‐192‐5p directly targeted ELAVL1 and decreased its expression. We further verified that ELAVL1 bound to PI3Kδ and maintained PI3Kδ mRNA stability. Rescue analysis demonstrated that the suppressive effects of HG‐treated HRMECs caused by miR‐192‐5p up‐regulation were overturned by overexpressed ELAVL1 or PI3Kδ.
Conclusion
MiR‐192‐5p attenuates DR progression by targeting ELAVL1 and reducing PI3Kδ expression, suggesting a biomarker for the treatment of DR.
Abstract
Orbit flips have been previously found under the eccentric Lidov–Kozai effect (ELK) in hierarchical three-body systems. Recently, we have found that, in certain conditions, the orbit can ...flip its orientation in a much different manner, where the stellar oblateness plays an important role. In this paper, orbit-flip behaviors with the ELK effect are investigated as the stellar oblateness varies within a wide range. This is of significance because recent works have shown that the oblateness of young stars has a widespread distribution and may have critical effects on sculpting the final orbital states of close-in planets. Our dynamical model includes the secular potential of the perturber to octupole order and the secular effects of the stellar oblateness. An alignment between the orbit plane of the outer perturber and the stellar bulge is assumed. Our findings mainly consist of two aspects. (i) A new type of orbit-flipping mechanism induced by a combination of the ELK and stellar oblateness effects, referred to as the ELK–
J
2
effect, is discovered and confirmed. (ii) We demonstrate that, in the considered aligned configuration, the stellar oblateness suppresses orbit flips due to the ELK effect and produces new flips through the ELK–
J
2
effect. Moreover, if the stellar oblateness perturbations are of the same order as the octupole perturbations of the outer perturber, the ELK-induced orbit flips are almost entirely suppressed, while the ELK–
J
2
effect reaches its peak for the considered strength of the octupole perturbations. However, from a global view, stellar oblateness always reduces flipping orbits.
•Carbonation pathways and carbon capture mechanisms of steel-making slags were summarized.•Effects of carbonation pathways on the carbonation capacity of steel-making slags were ...evaluated.•Carbonation products obtained from different carbonation pathways were analyzed and compared.•Scale-up applications and main challenges of steel-making slags carbonation technology are summarized and prospected.
With the rapid development of economy and industrialization, the consumption of natural resources has risen sharply. A large number of greenhouse gases and industrial solid waste emissions have exacerbated global warming, resulting in a series of environmental degradation problems. Using natural minerals or industrial solid waste for carbon dioxide capture and utilization (CCU) is considered to be a feasible and promising technology. From the perspective of circular economy, steel-making slag as carbon dioxide storage material has great economic and environmental value. This paper summarized the main carbonation pathways and carbon capture mechanisms of industrial solid wastes. The carbonation processes of the most representative solid waste of steel-making slags were compared, the effects of different carbonation pathways on the carbonation capacity of steel-making slags were evaluated, and the characteristics of carbonation products obtained from different carbonation pathways were also compared. In addition, the industrial application status of carbon dioxide carbonation technology of steel-making slags was analyzed, and the main challenges it faces were summarized and prospected. We hope that this review can attract extensive attention of scholars and promote the further development of carbon dioxide storage technology by mineralization of steel-making slag.
Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as ...cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus-induced microvascular dysfunction is largely unknown.
To elucidate whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes mellitus-induced microvascular dysfunction.
Using quantitative polymerase chain reaction, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes mellitus-induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a competing endogenous RNA, and formed a feedback loop with vascular endothelial growth factor and miR-150-5p to regulate endothelial cell function.
This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases.
Background:
Genetic characteristics remain underutilized for establishing prognostic models for colorectal cancer (CRC). We explored the underlying regulatory mechanisms of circular RNAs (circRNAs) ...that act as competing endogenous RNAs (ceRNAs) and constructed a gene-based nomogram to predict overall survival (OS) in patients with CRC.
Methods:
We obtained circRNA expression profiling data from the Gene Expression Omnibus (GEO) database. MicroRNA (miRNA) and mRNA expression profiles, with associated clinical data, were obtained from The Cancer Genome Atlas (TCGA). A ceRNA network was established using Cytoscape. Interactions between differential genes were analyzed, and hub genes were identified using the cytoHubba application. The R package “clusterProfiler” was used to evaluate the Gene Ontology (GO) annotations of the differentially expressed mRNAs and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Database-extracted patients were randomized into a training and validation cohorts. A prognostic model was developed using the training set based on multivariate Cox analyses and was then assessed in the validation set. The accuracy of the model was evaluated using discrimination and calibration plots.
Results:
Thirteen circRNAs, 62 miRNAs, and 301 mRNAs were used to construct the ceRNA network; 10 hub genes were identified via the PPI network. Next, a circRNA- miRNA hub of gene-regulatory modules was established based on four differentially expressed circRNAs, eight differentially expressed miRNAs, and nine differentially expressed mRNAs (DEmRNAs). GO and KEGG pathway analyses indicated the possible association of DEmRNAs with CRC onset and progression. Multivariate analyses revealed that age, tumor stage, and
CXCR5
expression were independent risk factors for OS. A
CXCR5
-based model was developed to predict the OS of patients with CRC in our training set. Our nomogram showed relatively good accuracy, with C-indices of 0.757 and 0.702 in the training and validation sets, respectively. The areas under the curve of the nomograms predicting 3- and 5-years OS were 0.749 and 0.805 in the training set and 0.706 and 0.779 in the validation set, respectively.
Conclusions:
Our data suggested that the hsa_circ_00001666/has-mir-1229/
CXCR5
axis plays an important role in the pathogenesis of CRC, thereby identifying a potential therapeutic target. The proposed
CXCR5
-based nomogram may also assist surgeons in devising personalized treatments for patients with this disease.
The formation of prismatic loops in metals has been studied extensively, but the corresponding research related to ceramics can rarely be found in the literature. In this article, the formation of ...prismatic loops in B4 ceramics under nanoindentation were investigated with molecular dynamics (MD) simulations. The indentation directions are respectively in the normal of the basal plane and the two prismatic planes in AlN and GaN single crystals. Two mechanisms for the formation of prismatic loop in B4 ceramics are found. One is the “lasso”-like mechanism, which is similar to that observed in metals, and the other is “nested-loops” mechanism, which has never been reported in the literature. MD simulations show that the screw segments of the two different shear loops, be adjacent to each other, can intersect with each other and finally produce a prismatic dislocation loop. The pile-up symmetry after unloading, associated with dislocation loops propagation, can be found, which is consistent with experimental results. More detailed analysis of dislocation patterns and directions indicate that plastic deformation is dominated by the shuffle-set dislocations along 13〈112¯0〉, and the glide-set dislocations along 13〈1¯010〉 are asymmetric.
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Diabetic retinopathy (DR) is a serious long‐term complication of diabetes. However, the current treatment of DR is still challenging. We aimed to investigate the role of lncRNA ...SNHG1/miR‐340‐5p/PIK3CA in DR and the mechanisms involved. Blood samples from clinical DR patients and healthy subjects were obtained. HRMECs were induced by high glucose for 24 h to establish the DR model. The vector for interfering or overexpressing lncRNA SNHG1, miR‐340‐5p, and PIK3CA was constructed. LncRNA SNHG1, miR‐340‐5p, and PIK3CA expressions were detected by qRT‐PCR or Western blot. Cell proliferation and migration were detected by CCK‐8 and Transwell assays. Blood vessel formation was detected by angiogenesis assay. Dual‐luciferase reporter assay tested the interaction of lncRNA SNHG1 with miR‐340‐5p and miR‐340‐5p with PIK3CA. RIP measured the binding of miR‐340‐5p to PIK3CA. In the blood of DR patients and the DR model, lncRNA SNHG1 was increased and miR‐340‐5p expression was down‐regulated. In the DR model, PIK3CA expression was elevated. Downregulation of lncRNA SNHG1 inhibited HRMECs proliferation, migration, and angiogenesis. LncRNA SNHG1 interacted with miR‐340‐5p, and up‐regulation of miR‐340‐5p inhibited HRMECs proliferation, migration and angiogenesis. The inhibition of cell proliferation, migration, and angiogenesis of HRMECs caused by down‐regulation of lncRNA SNHG1 was reversed by knockdown of miR‐340‐5p. miR‐340‐5p targeted PIK3CA, and downregulation of PIK3CA inhibited HRMECs proliferation, migration, and angiogenesis. The inhibition of HRMECs proliferation, migration and angiogenesis caused by down‐regulation of lncRNA SNHG1 could be reversed by overexpression of PIK3CA. LncRNA SNHG1 targeted miR‐340‐5p/PIK3CA axis to regulate microvascular endothelial cell proliferation, migration, and angiogenesis in DR.
Pyroptosis is a newly discovered programmed cell death that is associated with tumor progression, prognosis, and treatment response. However, the potential roles of pyroptosis-related genes (PRGs) in ...the tumor microenvironment (TME) remain unclear. We described the alterations of PRGs in 1109 colorectal cancer (CRC) samples from genetic and transcriptional fields and evaluated their expression patterns from four independent datasets. We identified two distinct molecular subtypes and found that multi-layer PRG alterations were correlated with patient clinicopathological features, prognosis, and TME cell-infiltrating characteristics. Then, a PRG_score for predicting recurrence-free survival (RFS) was constructed and its predictive capability in CRC patients was validated. Consequently, we constructed a highly accurate nomogram for improving the clinical applicability of the PRG_score. A low PRG_score, characterized by increased microsatellite instability-high (MSI-H), mutation burden, and immunity activation, indicated favorable odds of RFS. Moreover, the PRG_score was significantly associated with the cancer stem cell (CSC) index and chemotherapeutic drug sensitivity. Our comprehensive analysis of PRGs in CRC demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. These findings may improve our understanding of PRGs in CRC and pave a new path for the assessment of prognosis and the development of more effective immunotherapy strategies.
The shape memory polymer (SMP) is a new type of smart material that can produce a shape memory effect through the stimulation of the external environment. In this article, the viscoelastic ...constitutive theory of the shape memory polymer and the mechanism of the bidirectional memory effect of the shape memory polymer are described. A chiral poly cellular circular concave auxetic structure based on a shape memory polymer made of epoxy resin is designed. Two structural parameters, α and β, are defined, and the change rule of Poisson's ratio under different structural parameters is verified by ABAQUS. Then, two elastic scaffolds are designed to assist a new type of cellular structure made of a shape memory polymer to autonomously adjust bidirectional memory under the stimulation of the external temperature, and two processes of bidirectional memory are simulated using ABAQUS. Finally, when a shape memory polymer structure implements the bidirectional deformation programming process, a conclusion is drawn that changing the ratio β of oblique ligament and ring radius has a better effect than changing the angle α of oblique ligament and horizontal in achieving the autonomously adjustable bidirectional memory effect of the composite structure. In summary, through the combination of the new cell and the bidirectional deformation principle, the autonomous bidirectional deformation of the new cell is achieved. The research can be used in reconfigurable structures, tuning symmetry, and chirality. The adjusted Poisson's ratio achieved by the stimulation of the external environment can be used in active acoustic metamaterials, deployable devices, and biomedical devices. Meanwhile, this work provides a very meaningful reference for the potential application value of metamaterials.
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