Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typically characterized by chronic airway inflammation, with emerging evidence highlighting the driving role of cellular senescence-related lung aging. Accelerated lung aging and inflammation mutually reinforce each other, creating a detrimental cycle that contributes to disease progression. Growth arrest and DNA damage-inducible (GADD45) family has been reported to involve in multiple biological processes, including inflammation and senescence. However, the role of GADD45 family in COPD remains elusive.To investigate the role and mechanism of GADD45 family in COPD pathogenesis.Expressions of GADD45 family were evaluated by bioinformatic analysis combined with detections in clinical specimens. The effects of GADD45B on inflammation and senescence were investigated via constructing cell model with siRNA transfection or overexpression lentivirus infection and animal model with Gadd45b knockout. Targeted bisulfite sequencing was performed to probe the influence of DNA methylation in GADD45B expression in COPD.GADD45B expression was significantly increased in COPD patients and strongly associated with lung function, whereas other family members presented no changes. GADD45B upregulation was confirmed in mice exposed by cigarette smoke (CS) and HBE cells treated by CS extract as well. Moreover, experiments involving bidirectional modulation of GADD45B expression in HBE cells further substantiated its positive regulatory role in inflammatory response and cellular senescence. Mechanically, GADD45B-facilitated inflammation was directly mediated by p38 phosphorylation, while GADD45B interacted with FOS to promote cellular senescence in a p38 phosphorylation-independent manner. Furthermore, Gadd45b deficiency remarkably alleviated inflammation and senescence of lungs in CS-exposed mice, as well as improved emphysema and lung function. Eventually, in vivo and vitro experiments demonstrated that GADD45B overexpression was partially mediated by CS-induced DNA hypomethylation.Our findings have shed light on the impact of GADD45B in the pathogenesis of COPD, thereby offering a promising target for intervention in clinical settings. 

DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.

Steel-concrete-steel sandwich composite cable-pylon anchorage of cable-stayed bridges: horizontal bearing capacity

This paper designs the splicing GFRP-concrete-steel double-skin tubular column (DSTC) specimens based on steel bar connection, and the mechanical performance under eccentric compression load is investigated. The test parameters include the axial connection steel ratio, the load eccentricity and the hollow ratio. The results show that the splicing DSTCs present ductile failure under eccentric load, with the average deflection ductility coefficient of 4.21 and the axial shortening of more than 2% of the column height. The arranged connection steel cage prevents the joint failure, and the columns fail at the non-joint section, characterized by hoop rupture of the GFRP tube and concrete crushing at the same position. The proposed splice method satisfies the strength requirements, with more than 20% increase in the ultimate load compared with the continuous specimen, while the bearing capacity dose not increase with the increase of the axial connection steel ratio. Thus, it is suggested that the low axial steel ratio of 2.44% is used for the splicing DSTCs under relative small eccentricity (20 mm). The ultimate load decreases by about 25% with every 20 mm increase in load eccentricity, and the 40 mm eccentricity causes almost 50% reduction in the initial stiffness and doubles the lateral deflection compared with the axial compression member. The increase of hollow ratio decreases the ultimate load, the initial axial stiffness and also the ductility of the column. The theoretical calculation method for predicting the bearing capacity of the splicing DSTCs is experimentally verified.

Behavior of Splicing GFRP-Concrete-Steel Double-Skin Tubular Columns Subject to Eccentric Compression

Ground settlement is a critical issue in underground construction. Ground settlement prediction is important to identify serious damage to adjacent structures caused by settlement exceed the standard. However, conventional methods have some limitations due to nonlinearity and non-stationarity of settlement data. This paper proposes a hybrid model based on empirical model decomposition (EMD) and relevance vector machine(RVM) regression optimized by particle swarm optimization (PSO) designated as EMD-RVM. EMD is used to decompose the ground measured settlement time series into several stationary components called intrinsic mode functions (IMFs). Then, SVR is applied to predict the components independently. At last, the expected prediction values are the sum of all components prediction value at the same time. In order to validate the performance of the proposed method., the signal support vector regression(SVR), signal relevance vector machine(RVM) regression, relevance vector machine based on wavelet transform(WT-RVM) are used to be compared with root mean square error (RMSE) and mean absolute percentage Error(MAPE) are used to evaluate these models. The evaluation results indicate the method proposed is effective and practical.

/pdf/application-of-ground-settlement-prediction-based-on-emd-rvm-13dp2rtr70.pdf

Application of Ground Settlement Prediction Based on EMD-RVM

The utilization of vegetal fabric reinforced cementitious matrix (FRCM) represents an innovative approach to composite materials, offering distinct sustainable advantages when compared to traditional steel-reinforced concrete and conventional FRCM composites employing synthetic fibers. This article introduces a design for sandwich solutions based on a core of extruded polystyrene and composite skins combining mortar as a matrix and diverse vegetal fabrics as fabrics such as hemp and sisal. The structural behavior of the resulting sandwich panel is predominantly driven by the interaction between materials (mortar and polyurethane) and the influence of shear connectors penetrating the insulation layer. This study encompasses an experimental campaign involving double-shear tests, accompanied by heuristic bond-slip models for potential design of sandwich solutions. The analysis extends to the examination of various connector types, including hemp, sisal, and steel, and their impact on the shear performance of the sandwich specimens.&#x0D; The results obtained emphasize the competitiveness of vegetal fabrics in achieving effective composite strength comparable to other synthetic fabrics like glass fiber. Nevertheless, the study reveals that the stiffness of steel connectors outperforms vegetal connectors, contributing to an enhanced improvement in both stiffness and shear strength of the sandwich solutions 

Shear Performance of the Interface of Sandwich Specimens with FRCM Vegetal Fabric Skins

Shear resistance and deflection prediction of steel–concrete–steel sandwich panel with headed stud connectors

Interleukin-23 mediates the reduction of GADD45a expression to attenuate oxidative stress-induced cellular senescence in human fibroblasts

Based on an analysis of the developing mechanism of composite foundation settlement in combination with the characteristics of Verhulst gray model, a Verhulst gray model for the composite foundation settlement was specially developed to reflect the characteristics of settlement-time curve, such as its monotone increasing, boundedness and S-shape. The precision check proved that by such a Verhulst gray model less observing data are required to set up a prediction model with reliable precision through a mathematical reasoning process, which will reveal the long settlement process of composite foundation.

Modeling Prediction of Composite Foundation Settlement

Axial Compression Performance of Splicing Concrete-Filled GFRP Tubular Composite Component

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Shear resistance and deflection prediction of steel–concrete–steel sandwich panel with headed stud connectors

Interleukin-23 mediates the reduction of GADD45a expression to attenuate oxidative stress-induced cellular senescence in human fibroblasts

Modeling Prediction of Composite Foundation Settlement

Axial Compression Performance of Splicing Concrete-Filled GFRP Tubular Composite Component