Chronic obstructive pulmonary disease (COPD) patients are likely to develop sarcopenia, while the exact mechanism underlying the association between sarcopenia and COPD is still not clear. This ...cohort study aims to explore the genes, signaling pathways, and transcription factors (TFs) that are related to the molecular pathogenesis of sarcopenia and COPD.
According to the strict inclusion criteria, two gene sets (GSE8479 for sarcopenia and GSE76925 for COPD) were obtained from the Gene Expression Omnibus (GEO) platform. Overlapping differentially expressed genes (DEGs) in sarcopenia and COPD were detected, and comprehensive bioinformatics analysis was conducted, including functional annotation, enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), construction of a protein–protein interaction (PPI) network, co-expression analysis, identification and validation of hub genes, and TFs prediction and verification.
In total, 118 downregulated and 92 upregulated common DEGs were detected. Functional analysis revealed that potential pathogenesis involves oxidoreductase activity and ferroptosis. Thirty hub genes were detected, and ATP metabolic process and oxidative phosphorylation were identified to be closely related to the hub genes. Validation analysis revealed that SAA1, C3, and ACSS2 were significantly upregulated, whereas ATF4, PPARGC1A, and MCTS1 were markedly downregulated in both sarcopenia and COPD. In addition, six TFs (NFKB1, RELA, IRF7, SP1, MYC, and JUN) were identified to regulate the expression of these genes, and SAA1 was found to be coregulated by NFKB1 and RELA.
This study uncovers potential common mechanisms of COPD complicated by sarcopenia. The hub gene SAA1 and the NF-κB signaling pathway could be involved, and oxidative phosphorylation and ferroptosis might be important contributors to this comorbidity.
•Similar pathophysiological factors could play a role in both COPD and sarcopenia.•Oxidative phosphorylation is closely related to the overlapped hub genes.•SAA1 was coordinately regulated by transcription factors of NFKB1 and RELA.•SAA1 and NF-κB signaling pathway may implicate in sarcopenia complicated with COPD.
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial ...permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.
•Curcumin protected neurons against Aβ25–35-induced apoptosis.•Curcumin attenuated Aβ25–35-induced ROS generation and rescued mitochondrial function.•Curcumin inhibited Aβ25–35 toxicity via ...increasing the expression of SIRT1 and decreasing the expression of Bax.•SIRT1 siRNA blocked the protection of curcumin in Aβ milieu.
As one of the most important hallmarks of Alzheimer’s disease (AD), β-amyloid (Aβ) plays important roles in inducing reactive oxygen species (ROS) generation, mitochondrial dysfunction and apoptotic cell death in neurons. Curcumin extracted from the yellow pigments spice plant turmeric shows multiplied bioactivities such as antioxidant and anti-apoptosis properties in vitro and in vivo. In the present study, the neuroprotective effect of curcumin against Aβ25–35-induced cell death in cultured cortical neurons was investigated. We found that pretreatment of curcumin prevented the cultured cortical neurons from Aβ25–35-induced cell toxicity. In addition, curcumin improved mitochondrial membrane potential (ΔΨm), decreased ROS generation and inhibited apoptotic cell death in Aβ25–35 treated neurons. Furthermore, we found that application of curcumin activated the expression of SIRT1 and subsequently decreased the expression of Bax in the presence of Aβ25–35. The protective effect of curcumin was blocked by SIRT1 siRNA. Taken together, our results suggest that activation of SIRT1 is involved in the neuroprotective action of curcumin.
Landslides, as a representative geohazard in fault zones, threaten the safety of buildings and infrastructure. Landslide movements are often subject to multiple loads in urbanized hillslopes from ...both natural and human activity. Synthetic aperture radar interferometry (InSAR) has been used to measure landslide movements. Used independently, InSAR can measure only surface deformation, and the points are sparse. Numerical modeling can simulate the full-scale movements, but it requires a prior knowledge of soil properties that are often not available in practice. To address these limitations, we proposed to couple InSAR and numerical modeling for characterizing landslide movements under multiple loads. We used 60 ascending and 56 descending Sentinel-1 images to measure surface movements in urbanized Daguan County Town. Of 31 landslides in the inventory map, 24 were successfully identified. The InSAR results assisted in determining the optimal soil properties through back-analysis. We used geological, geotechnical, and meteorological data to set three boundary conditions, that is, body loads, precipitation-induced hydraulic conditions, and construction-induced forces. Landslide mobility was demonstrated more distinctly using the coupled analysis. The numerical results revealed that body loads dominated the cumulative downslope movements by squeezing water and air from voids, and precipitation caused seasonal movements with the direction perpendicular to the slope surface. Construction works caused permanent changes (accelerating and decelerating) in time-series trends. Coupling InSAR and numerical modeling can facilitate analysis of the effects of complex loads and potentially predict future deformation. The method developed can be extended to study other urbanized landslide areas for early warning and risk mitigation.
A 3-D Shenzhen City Web platform based on the Web virtual reality geographical information system is presented. A 3-D global browser is employed to load multiple types of demand data from the city, ...such as 3-D building model data, residents' information, and real-time and historical traffic data. Using these data, a 3-D analysis and visualization of the city's information are conducted on a platform. The amount of information that can be visualized with this platform is very large, and the GIS-based navigational scheme enables great flexibility to access different available data sources. All the presented functions of the platform are extracted from the customers' practical demand. The system design considers some existing geographic human-computer interaction research results.
The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or ...transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOP
, EZH1
and ZNF148 mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin.
Background:
Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy associated with poor clinical outcome. As a novel form of cell death, ferroptosis is reliant on the accumulation of iron ...and reactive oxygen species and is involved in the pathogenesis of various tumors, including ACC. Our study aimed to identify and characterize the prognostic ferroptosis-related lncRNA signature (FerRLSig) in ACC.
Methods:
A regulatory network of ferroptosis-related lncRNAs (FerRLs) and mRNAs was constructed based on The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression assays were performed to construct the FerRLSig.
Results:
Twenty-four FerRLs were identified in the prognostic model, and the high-risk FerRLSig was related to the worse overall survival (OS) in ACC hazard ratio (HR): 1.936 (1.484–2.526),
p
< 0.001. The area under the curve (AUC) value of the FerRLSig was 0.936 according to the receiver operating characteristic (ROC) analyses, superior to other traditional clinicopathological features, further supported the utility in prognosis prediction of ACC. We further established a prognostic nomogram combining clinical factors with the FerRLSig, which showed favorable efficacy for survival prediction. Next, gene set enrichment analysis (GSEA) revealed that gene sets were involved in many immune regulatory biological processes related to malignancies. T-cell function of type II INF response and the immune checkpoints, including CD40, CD276, IDO2, NRP1, and CD80, were expressed with a significant difference between the low- and high-risk groups.
Conclusion:
This study offered new insights into the pathogenesis of ACC. The novel FerRLSig could be useful in predicting survival and may provide information of immunological research and treatment for ACC patients.
Street tree extraction based on the 3-D mobile mapping point cloud plays an important role in building smart cities and creating highly accurate urban street maps. Existing methods are often over- or ...under-segmented when segmenting overlapping street tree canopies and extracting geometrically complex trees. To address this problem, we propose a method based on improved 3-D morphological analysis for extracting street trees from mobile laser scanner (MLS) point clouds. First, the 3-D semantic point cloud segmentation framework based on deep learning is used for preclassification of the original point cloud to obtain the vegetation point cloud in the scene. Considering the influence of terrain unevenness, the vegetation point cloud is deterraformed and slice point cloud containing tree trunks is obtained through spatial filtering on height. On this basis, a voxel-based region growing method constrained with the changing rate of convex area is used to locate the stree trees. Then we propose a progressive tree crown segmentation method, which first completed the preliminary individual segmentation of the tree crown point cloud based on the voxel-based region growth constrained by the minimum increment rule, and then optimizes the crown edges by “valley” structure-based clustering. In this article, the proposed method is validated and the accuracy is evaluated using three sets of MLS datasets collected from different scenarios. The experimental results show that the method can effectively identify and localize street trees with different geometries and has a good segmentation effect for street trees with large adhesion between canopies. The accuracy and recall of tree localization are higher than 96.08% and 95.83%, respectively, and the average precision and recall of instance segmentation in three datasets are higher than 93.23% and 95.41%, respectively.
As an essential part of point cloud processing, autonomous classification is conventionally used in various multifaceted scenes and non-regular point distributions. State-of-the-art point cloud ...classification methods mostly process raw point clouds, using a single point as the basic unit and calculating point cloud features by searching local neighbors via the k-neighborhood method. Such methods tend to be computationally inefficient and have difficulty obtaining accurate feature descriptions due to inappropriate neighborhood selection. In this paper, we propose a robust and effective point cloud classification approach that integrates point cloud supervoxels and their locally convex connected patches into a random forest classifier, which effectively improves the point cloud feature calculation accuracy and reduces the computational cost. Considering the different types of point cloud feature descriptions, we divide features into three categories (point-based, eigen-based, and grid-based) and accordingly design three distinct feature calculation strategies to improve feature reliability. Two International Society of Photogrammetry and Remote Sensing benchmark tests show that the proposed method achieves state-of-the-art performance, with average F1-scores of 89.16 and 83.58, respectively. The successful classification of point clouds with great variation in elevation also demonstrates the reliability of the proposed method in challenging scenes.
Mutations in NF1 cause neurofibromatosis type I (NF1), a disorder characterized, among other clinical manifestations, by generalized and focal bony lesions. Dystrophic scoliosis and tibial ...pseudoarthrosis are the most severe skeletal manifestations for which treatment is not satisfactory, emphasizing the dearth of knowledge related to the biology of NF1 in bone cells. Using reporter mice, we report here that the mouse Col2α1-Cre promoter (collagen, type II, alpha 1) is active not only in chondrocytes but also in adult bone marrow osteoprogenitors giving rise to osteoblasts. Based on this finding, we crossed the Col2α1-Cre transgenic and Nf1
flox/flox
mice to determine whether loss of Nf1 in axial and appendicular osteochondroprogenitors recapitulates the skeletal abnormalities of NF1 patients. By microtomographic and X-rays studies, we show that Nf1Col2
−/−
mice display progressive scoliosis and kyphosis, tibial bowing and abnormalities in skull and anterior chest wall formation. These defects were accompanied by a low bone mass phenotype, high bone cortical porosity, osteoidosis, increased osteoclastogenesis and decreased osteoblast number, as quantified by histomorphometry and 3D-microtomography. Loss of Nf1 in osteochondroprogenitors also caused severe short stature and intervertebral disc defects. Blockade of the RAS/ERK activation characteristic of Nf1
−/−
osteoprogenitors by lovastatin during embryonic development could attenuate the increased cortical porosity observed in mutant pups. These data and the skeletal similarities between this mouse model and NF1 patients thus suggest that activation of the RAS/ERK pathway by Nf1 loss-of-function in osteochondroprogenitors is responsible for the vertebral and tibia lesions in NF1 patients, and that this molecular signature may represent a good therapeutic target.
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