Explore the vast range of titles available.

Background Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold.

Transforming growth factor‐β (TGF‐β) is known to promote breast cancer cell migration, invasion, and dissemination; however, the underlying molecular mechanisms are not yet well characterized. Here, we report that TGF‐β induces pleckstrin‐2 (PLEK2) expression by Smad3 and signal transducer and activator of transcription 3 (STAT3) activating PLEK2 promoter activity. Higher PLEK2 expression is associated with poor prognosis in breast cancer patients. Overexpression and knockout experiments in MDA‐MB‐231 and MCF‐7 breast cancer cells revealed that PLEK2 promotes cell migration, invasion, and dissemination in 2D and 3D cell culture. Moreover, PLEK2 promotes metastasis of breast cancer cells in vivo. Pleckstrin‐2 localizes to the cell membrane and cell protrusions following TGF‐β treatment. Furthermore, inhibition of PI3K phosphorylation abolishes TGF‐β‐ and PLEK2‐induced cell invasion. The carboxyl‐terminal PH domain of PLEK2 is critical for TGF‐β‐ and PLEK2‐induced Akt activation and plays an important role in cell invasion. Pleckstrin‐2 interacts with PPM1B and promotes its ubiquitin‐dependent degradation. The PLEK2‐PPM1B axis utilizes nuclear factor‐κB signaling to promote cell migration and invasion. Our data implicate the TGF‐β‐STAT3/Smad3‐PLEK2‐PPM1B signaling cascade in TGF‐β‐induced breast cancer cell migration and invasion. These findings suggest that PLEK2/PPM1B could represent novel targets for the intervention of breast cancer metastasis. Our results revealed the TGF‐β‐STAT3/Smad3‐PLEK2‐PPM1B signaling cascade in TGF‐β‐induced breast cancer cell migration and invasion. These findings suggest that PLEK2/PPM1B may represent novel targets for breast cancer metastasis intervention.

Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC), and approximately 20% of patients experience treatment failure due to tumour radioresistance. However, the exact regulatory mechanism remains poorly understood. Here, we show that the deubiquitinase USP44 is hypermethylated in NPC, which results in its downregulation. USP44 enhances the sensitivity of NPC cells to radiotherapy in vitro and in vivo. USP44 recruits and stabilizes the E3 ubiquitin ligase TRIM25 by removing its K48-linked polyubiquitin chains at Lys439, which further facilitates the degradation of Ku80 and inhibits its recruitment to DNA double-strand breaks (DSBs), thus enhancing DNA damage and inhibiting DNA repair via non-homologous end joining (NHEJ). Knockout of TRIM25 reverses the radiotherapy sensitization effect of USP44. Clinically, low expression of USP44 indicates a poor prognosis and facilitates tumour relapse in NPC patients. This study suggests the USP44-TRIM25-Ku80 axis provides potential therapeutic targets for NPC patients. Radiotherapy is the mainstay treatment for nasopharyngeal carcinoma (NPC). Here the authors show that the deubiquitinase, USP44, increases radiosensitivity of NPC cells by promoting the degradation of Ku80, and thus enhancing the levels of DNA damage.

Background The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3. Methods The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining. Results Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD. Conclusion PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.

As the requirement for image uploads in various systems continues to grow, image segmentation has become a critical task for subsequent operations. Balancing the efficiency and accuracy of image segmentation is a persistent challenge. This paper focuses on threshold-based grayscale image segmentation methods and proposes a fully automated approach. The approach begins with the implementation of an improved OTSU algorithm to determine the optimal dynamic threshold, enabling the segmentation process to adjust adaptively to varying image backgrounds. A novel method for selecting image center points is introduced to address the issue of poor segmentation when the center point falls outside the segmentation foreground area. To further enhance the algorithm’s generalization capability and accuracy, a continuity detection-based method is developed to determine the start and end points of the segmentation foreground. Compared with traditional algorithms, tests on sample images of four different scales revealed that the proposed algorithm achieved average improvements in accuracy, precision, and recall rates of 14.97%, 1.28%, and 17.33%, respectively, with processing speed remaining largely unaffected. Ablation experiments further validated the effectiveness of using different strategy combinations, with the combination of all three strategies resulting in significant improvements in accuracy and recall rates by 15.51% and 16.72%, respectively.

The potential risks of osteoarthritis (OA) progression in the lateral compartment during the progression of medial knee OA and after medial unicompartmental knee arthroplasty (UKA) remain to be elucidated. Thus, five medial knee OA models with different progression stages and one medial UKA model were established using the finite element method to investigate the biomechanical differences of lateral compartment articular cartilage (AC). The AC and meniscus were constructed by fibril-reinforced biphasic material, and the real biphasic contact conditions were adopted. The results showed that biomechanical differences in lateral compartments were within 2% between the healthy knee model (OARSI 0–1) and early medial knee OA models (OARSI 2–3). However, in advanced medial knee OA (OARSI 4.5), up to a 7.0% increase in stress and a 22.2% increase in a strain of the lateral compartment AC were predicted. After medial UKA surgery, the maximum shear strain of the lateral compartment AC was reduced by about 22.2% when compared with advanced medial knee OA. In conclusion, the progression of medial knee OA may cause OA development in the lateral compartment. In contrast, medial UKA surgery might help to lower the risks of OA progression in the lateral compartment when in the advanced medial knee OA stage.

Purpose This study aims to examine the relationship between board capital and firm performance in the Chinese tourism industry. Design/methodology/approach The study’s sample includes firms from the Chinese hotel, air transportation/travel and catering industries. This study explores the governance environment in tourism industries. This study estimates three dimensions of the board, including education, expertise and directors interlock. These dimensions are further grouped as human capital (i.e. education and expertise), social capital (interlocks) and board capital (sum of social and human capital). Ordinary least square regressions with multiple robustness tests are used to investigate the effect of board capital on firm value in Chinese listed tourism firms during 2005–2018. Findings This study finds that board capital positively impacts firm performance in its dimensions of human and social capital. This study also highlights the two important ownership contexts, namely, institutional investors and state-ownership, that shape the board capital-firm performance association in the Chinese tourism industry. Practical implications The findings suggest that board capital plays a significant role in corporate decisions. The results illustrate that higher board capital improves both governance mechanisms and resource provision roles of the board, resulting in higher firm value. The results further offer implications for managers and shareholders of tourism firms when electing directors as shareholders’ representatives. Originality/value The study has two important contributions. First, it extends the prior literature of firm value by considering the board’s human and social dimensions in the tourism sector. Second, contrary to prior research on board, this study takes three facets of board capital, education, expertise and interlocks that improve governance mechanisms and bring new resources in the shape of skills, knowledge and expertise.

A risk factor for thyroid cancer (TC) may be a history of former cancer and cancer therapy. The precise risk of a second primary thyroid carcinoma has not yet been revealed. In this study, we evaluated standardized incidence ratios (SIRs) of second primary thyroid cancer (SPTC) with consideration of different conditions and further analyzed the clinicopathological characteristics and survival of these patients. The cohort was selected from the US Surveillance, Epidemiology, and End Results (SEER) Program between 1975 and 2019. The standardized incidence ratios, morbidity risk, clinicopathological features, and survival of second primary thyroid carcinoma were analyzed. Propensity score matching (PSM) was used to balance covariates. Kaplan–Meier method was performed to assess the survival outcomes. Overall, 7066 patients with SPTC and 83,113 patients with primary TC were identified. The SIR of TC in tumor patients was 1.51/10,000, statistically higher than the natural population (0.94/10,000, P < 0.05). The most significant tumors contributing to the increased SIRs of SPTC were acute lymphocytic leukemia (3.49/10,000), Hodgkin’s lymphoma-nodal (3.29/10,000), salivary gland cancer (3.23/10,000), and kidney and renal pelvis cancer (3.05/10,000). The incidence of TC increased significantly in tumor patients who received radiotherapy/chemotherapy before age 35. The age at diagnosis of the SPTC was much older than the primary TC (64.01 vs. 49.55 years, p < 0.001). The SPTC had a higher percentage of histological grades 3/4 (23.14% vs. 15.19%, p < 0.001). Survival analyses demonstrated a worse prognosis for the SPTC group compared to the primary TC group. But after PSM, the survival outcomes of the two groups tended to be equivalent (P = 0.584). The SIRs of TC are higher in tumor patients. The most significant factors contributing to the increased risk of SPTC were some specific former tumors and acceptance of radiotherapy/ chemotherapy before age 35. There was no significant difference in survival between SPTC and primary TC.

Addressing the current reliance on manual sorting and grading of spray rose cut flowers, this paper proposed an improved YOLOv5s model for intelligent recognition and grading detection of rose color series and flowering index of spray rose cut flowers. By incorporating small-scale anchor boxes and small object feature output, the model enhanced the annotation accuracy and the detection precision for occluded rose flowers. Additionally, a convolutional block attention module attention mechanism was integrated into the original network structure to improve the model’s feature extraction capability. The WIoU loss function was employed in place of the original CIoU loss function to increase the precision of the model’s post-detection processing. Test results indicated that for two types of spray rose cut flowers, Orange Bubbles and Yellow Bubbles, the improved YOLOv5s model achieved an accuracy and recall improvement of 10.2% and 20.0%, respectively. For randomly collected images of spray rose bouquets, the model maintained a detection accuracy of 95% at a confidence threshold of 0.8.