Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and ...articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin-mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.
Severe weather and long-term driving of vehicles lead to various cracks on asphalt pavement. If these cracks cannot be found and repaired in time, it will have a negative impact on the safe driving ...of vehicles. Traditional artificial detection has some problems, such as low efficiency and missing detection. The detection model based on machine learning needs artificial design of pavement crack characteristics. According to the pavement distress identification manual proposed by the Federal Highway Administration (FHWA), these categories have three different types of cracks, such as fatigue, longitudinal crack, and transverse cracks. In the face of many types of pavement cracks, it is difficult to design a general feature extraction model to extract pavement crack features, which leads to the poor effect of the automatic detection model based on machine learning. Object detection based on the deep learning model has achieved good results in many fields. As a result, those models have become possible for pavement crack detection. This paper discusses the latest YOLOv5 series detection model for pavement crack detection and is to find out an effective training and detection method. Firstly, the 3001 asphalt crack pavement images with the original size of 2976×3978 pixels are collected using a digital camera and are randomly divided into three types according to the severity levels of low, medium, and high. Then, for the dataset of crack pavement, YOLOv5 series models are used for training and testing. The experimental results show that the detection accuracy of the YOLOv5l model is the highest, reaching 88.1%, and the detection time of the YOLOv5s model is the shortest, only 11.1 ms for each image.
Cobalt-based and nickel-based coatings were successfully produced using TIG welding and laser cladding technologies as alternative materials with higher cavitation erosion (CE) and slurry erosion ...(SE) resistance, respectively. Their structure, phase constitution, hardness and elastoplasticity were characterized. Combined with the cumulative mass loss, erosion morphology and roughness, the CE and SE resistances were compared and erosion models were also proposed. The results show that the cobalt-based coating exhibited much better CE resistance and lower SE resistance than the nickel-based coating. The phase transition contributes mostly to the high CE resistance of the cobalt-based coating. While, the combined effects of high hardness, elastoplasticity and hard phases' anchoring and shielding, determine the high SE resistance of the nickel-based coating.
•TIG welding Co- and laser cladding Ni-based coatings were performed respectively.•Ni-based coating has higher hardness and elastoplasticity than the Co-coating.•Co-based coating has higher cavitation erosion but lower slurry erosion resistance.•Phase transition effectively resists the cavitation erosion of Co-based coating.•Anchoring of the hard phases favors the high SE resistance of Nickel-based coating.
Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As denosumab achieves greater ...remodeling suppression and lower cortical porosity than alendronate, we hypothesized that denosumab might also preserve trabecular plate microstructure, bone stiffness and strength more effectively than alendronate.
In this post hoc analysis of a phase 2 study, postmenopausal women randomized to placebo (P, n = 74), denosumab (D, n = 72), or alendronate (A, n = 68). HR-pQCT scans of the distal radius and tibia were performed at baseline and Month-12 (M12). Trabecular compartment was subjected to Individual Trabecula Segmentation while finite element analysis was performed to estimate stiffness and strength. Percent change from baseline at M12 of each parameter was compared between patient groups.
At the distal tibia, in the placebo group, plate surface area (pTb.S, −1.3%) decreased while rod bone volume fraction (rBV/TV, +4.5%) and number (rTb.N, +2.1%) increased. These changes were prevented by denosumab but persisted despite alendronate therapy (pTb.S: −1.7%; rBV/TV: +6.9%; rTb.N: +3.0%). Both treatments improved whole bone stiffness (D: +3.1%; A: +1.8%) and failure load (D: +3.0%; A: +2.2%); improvements using denosumab was significant compared to placebo (stiffness: p = 0.004; failure load: p = 0.003). At the distal radius, denosumab increased total trabecular bone volume fraction (BV/TV, +3.4%) and whole bone failure load (+4.0%), significantly different from placebo (BV/TV: p = 0.044; failure load: p = 0.046). Significantly different effects of either drug on plate and rod microstructure were not detected.
Denosumab preserved trabecular plate microstructure. Alendronate did not. However, estimated strength did not differ between denosumab and alendronate treated groups.
Understanding the relationship between the microstructure and mechanical function of trabecular bone is critical for prediction and prevention of bone fragility fractures. However, a detailed ...understanding of the structural design of trabecular microarchitecture is still missing. This study hypothesized that there exists a commonality in the underlying probabilistic distributions of microstructural features of trabecular bones, whereas the microstructural differences among individuals are primarily describe by a set of scalar parameters. To test the hypothesis, twenty-three trabecular bone specimens were obtained from two anatomic locations (i.e., femoral neck and vertebral body) and a diverse group of seventeen donors of different age and sex. The number, size, spatial location, and orientation of individual plates and rods in the trabecular bone specimens were determined via volumetric decomposition of 3D μCT images using the Individual Trabecula Segmentation (ITS) technique. Then, m/n bootstrap Kolmogorov-Smirnov tests were performed to compare the normalized distributions of size, orientation, and spatial arrangement of trabecular plates and rods in the specimens. The results showed that 100% of the twenty-three normalized distributions of each microstructural feature were statistically equivalent irrespective of individual differences among the bone specimens, except the distributions of rod spatial arrangement (<100%). On the other hand, nonparametric Mann-Whitney U tests showed that a set of scalar parameters (i.e., the number, average size, and average nearest neighbor distance of trabecular plates and rods) were statistically different among the individual specimens (p<0.05). Due to the commonality of the underlying distributions, the individual differences in the trabecular microstructure among the specimens seemed to be reflected primarily by changes in the scalar parameters. The above results strongly support the hypothesis of this study and may shed more light on understanding the natural design of trabecular bone microstructures.
•Commonality exists in the distributions of microstructural features of trabeculae.•Microstructural scalar parameters capture individual differences among donors.•Common distributions and scalar parameters can describe trabecular microstructure.•Scalar parameters are more informative than current morphological parameters.•Underlying commonality provides a foundation for digital models of trabecular bone.
Dynamic headspace sampling (DHS) coupled with gas chromatography–mass spectrometry and olfactometry (GC–MS–O) analysis have been applied for the determination of the characteristic volatile profile ...of propolis with the aim to differentiate the propolis from different regions of China. Acids, esters, alcohols, terpenes, aromatics represented the most abundant compounds in propolis among the ninety-nine volatile components identified by comparing with mass spectra and retention indices (RI) or from literature. In addition, principal component analysis (PCA) based on the data of DHS–GC–MS and electronic nose was used to study and obtain the important volatile compounds contributed to the differentiation of the propolis samples from different regions. Furthermore, a total of 28 odor-active compounds were detected and characterized by the trained panel of judges in the sniffing port of GC–O by using detection frequency analysis (DFA). In conclusion, GC–MS analysis and electronic nose combining with PCA could successfully distinguish the twelve representative raw propolis samples from 4 different geographical regions of China. The samples have been assigned to four large groups in accordance with their vegetal sampling location and we also have observed the volatile compounds resulting in the odor differentiation.
► DHS/GC–MS was applied for the determination of the volatile profile of propolis. ► The identification of the geographical origin of propolis was carried out. ► The propolis samples were discriminated by GC–MS coupled with PCA method. ► The propolis samples were discriminated by electronic nose coupled with PCA. ► GC–O was used to identify aroma-active components of propolis.
The multidrug resistance and distant metastasis of cholangiocarcinoma result in high postoperative recurrence and low long-term survival rates. It has been demonstrated that the ectopic expression of ...miR-200 suppresses the multidrug resistance and metastasis of cancer. However, the expression and function of miR-200 in cholangiocarcinoma has not yet been described.
In this study, we identified dysregulated microRNAs (miRNAs, miR) in cholangiocarcinoma tissue by microarray analysis, and subsequent real-time PCR and northern blot analyses validated the expression of candidate miR. We performed functional analyses and investigated the relationship between miR-200b/c expression and the properties of cholangiocarcinoma cells. A dual luciferase assay was applied to examine the effect of miRNAs on the 3'-UTR of target genes, and we demonstrated the function of the target gene by siRNA transfection identifying the downstream pathway via western blotting.
We found significantly downregulated expression of four miR-200 family members (miR-200a/b/c/429) and then confirmed that ectopic miR-200b/200c inhibits the migration and invasion of cholangiocarcinoma cells both in vitro and in vivo. We found that miR-200b/c influenced the tumourigenesis of cholangiocarcinoma cells including their tumour-initiating capacity, sphere formation, and drug resistance. We further found that miR-200b/c regulated migration and invasion capacities by directly targeting rho-kinase 2 and regulated tumorigenic properties by directly targeting SUZ12 (a subunit of a polycomb repressor complex).
Our study shows that miR-200b/c has a critical role in the regulation of the tumorigenic and metastatic capacity of cholangiocarcinoma and reveals the probable underlying mechanisms.
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