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Cancer cell mechanotype changes are newly recognized cancer phenotypic events, whereas metastatic cancer cells show decreased cell stiffness and increased deformability relative to normal cells. To further examine how cell mechanotype changes in early stages of cancer transformation and progression, an in vitro multi-step human urothelial cell carcinogenic model was used to measure cellular Young's modulus, deformability, and transit time using single-cell atomic force microscopy, microfluidic-based deformability cytometry, and quantitative deformability cytometry, respectively. Measurable cell mechanotype changes of stiffness, deformability, and cell transit time occur early in the transformation process. As cells progress from normal, to preinvasive, to invasive cells, Young's modulus of stiffness decreases and deformability increases gradually. These changes were confirmed in three-dimensional cultured microtumor masses and urine exfoliated cells directly from patients. Using gene screening and proteomics approaches, we found that the main molecular pathway implicated in cell mechanotype changes appears to be epithelial to mesenchymal transition.

The present study aims to investigate the advantages of diamond-like carbon (DLC) films in reducing friction and lubrication to address issues such as the low surface hardness, high friction coefficients, and poor wear resistance of titanium alloys. Cr-doped DLC films were deposited by high-power impulse magnetron sputtering (HiPIMS) in an atmosphere of a gas mixture of Ar and C2H2. The energy of the deposited particles was controlled by adjusting the target powers, and four sets of film samples with different powers (4 kW, 8 kW, 12 kW, and 16 kW) were fabricated. The results showed that with an increase in target power, the Cr content increased from 3.73 at. % to 22.65 at. %; meanwhile, the microstructure of the film evolved from an amorphous feature to a nanocomposite structure, with carbide embedded in an amorphous carbon matrix. The sp2-C bond content was also increased in films, suggesting an intensification of the film's graphitization. The hardness of films exhibited a trend of initially increasing and then decreasing, reaching the maximum value at 12 kW. The friction coefficient and wear rate of films showed a reverse trend compared to hardness variation, namely initially decreasing and then increasing. The friction coefficient reached a minimum value of 0.14, and the wear rate was 2.50 × 10−7 (mm3)/(N·m), at 8 kW. The abrasive wear was the primary wear mechanism for films deposited at a higher target power. Therefore, by adjusting the target power parameter, it is possible to control the content of the metal and sp2/sp3 bonds in metal-doped DLC films, thereby regulating the mechanical and tribological properties of the films and providing an effective approach for addressing surface issues in titanium alloys. [ABSTRACT FROM AUTHOR]

Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The β-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter.

Brain tissue segmentation plays a critical role in the diagnosis, treatment, and study of brain diseases. Accurately identifying these boundaries is essential for improving segmentation accuracy. However, distinguishing boundaries between different brain tissues can be challenging, as they often overlap. Existing deep learning methods primarily calculate the overall segmentation results without adequately addressing local regions, leading to error propagation and mis-segmentation along boundaries. In this study, we propose a novel mis-segmentation-focused loss function based on a two-stage nnU-Net framework. Our approach aims to enhance the model's ability to handle ambiguous boundaries and overlapping anatomical structures, thereby achieving more accurate brain tissue segmentation results. Specifically, the first stage targets the identification of mis-segmentation regions using a global loss function, while the second stage involves defining a mis-segmentation loss function to adaptively adjust the model, thus improving its capability to handle ambiguous boundaries and overlapping anatomical structures. Experimental evaluations on two datasets demonstrate that our proposed method outperforms existing approaches both quantitatively and qualitatively. [ABSTRACT FROM AUTHOR]

Background: Despite the favorable clinical outcome of percutaneous kyphoplasty (PKP) in symptomatic osteoporotic vertebral fractures (OVFs) patients with intravertebral clefts (IVCs), previous studies have demonstrated a high incidence of augmented vertebrae recompression (AVR). We aim to evaluate the usefulness of the adjacent and injured vertebral bone quality scores (VBQS) based on T1‐weighted MRI images in AVR after PKP for OVFs with IVCs. Methods: Patients who underwent PKP for single OVFs with IVCs between January 2014 and September 2020 were reviewed and met the inclusion criteria. The follow‐up period was at least 2 years. Relevant data affecting AVR were collected. Pearson and Spearman correlation coefficients were used to calculate the correlation between the injured and adjacent VBQS and BMD T‐score. We determined independent risk factors and critical values using binary logistic regression analysis and receiver operating characteristic curves (ROC). Results: A total of 165 patients were included. Recompression group was found in 42 (25.5%) patients. The independent risk factors for AVR were lumbar BMD T‐score (OR = 2.53, p = 0.003), the adjacent VBQS (OR = 0.79, p = 0.016), the injured VBQS (OR = 1.27, p = 0.048), the ratio of adjacent to injured VBQS (OR = 0.32, p < 0.001), and cement distribution pattern. Among these independent significant risk factors, the prediction accuracy of the ratio of adjacent to injured VBQS was the highest (Cutoff = 1.41, AUC = 0.753). Additionally, adjacent and injured VBQS were negatively correlated with lumbar BMD T‐scores. Conclusion: For the patients after PKP treatment for OVFs with IVCs, the ratio of adjacent to injured VBQS had the best prediction accuracy in predicting recompression and when the ratio of adjacent to injured VBQS was <1.41, the augmented vertebrae were more likely to have recompression in the future. [ABSTRACT FROM AUTHOR]