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Abstract Matrix Metalloproteinases (MMPs) have been demonstrated to be essential in facilitating the migration and metastasis of clear cell renal cell carcinoma (ccRCC). However, the ability of the MMP family to predict clinical outcomes and guide optimal therapeutic strategies for ccRCC patients remains incompletely understood. In this investigation, we initially conducted a thorough examination of the MMP family in pan-cancer. Notably, MMPs exhibited distinctive significance in ccRCC. Following this, we undertook an extensive analysis to evaluate the clinical value of MMPs and potential mechanisms by which MMPs contribute to the progression of ccRCC. A novel stratification method and prognostic model were developed based on MMPs in order to enhance the accuracy of prognosis prediction for ccRCC patients and facilitate personalized treatment. By conducting multi-omics analysis and transcriptional regulation analysis, it was hypothesized that SAA1 plays a crucial role in promoting ccRCC migration through MMPs. Subsequently, in vitro experiments confirmed that SAA1 regulates ccRCC cell migration via the ERK-AP1-MMPs axis. In conclusion, our study has explored the potential value of the MMP family as prognostic markers for ccRCC and as guides for medication regimens. Additionally, we have identified SAA1 as a crucial factor in the migration of ccRCC.

As a technological advantage of ultrasonic non-destructive testing, fully focused imaging can accurately feedback the defective characteristics of the inspected object, greatly improving the detection efficiency. This article aims to address the challenges of outdated and low detection rates in the detection technology of branch pipe fillet welds. The full matrix acquisition (FMC) and total focus method (TFM) ultrasonic detection technology are used for detection and defect image feature analysis. Firstly, a multi-mode, fully focused real-time imaging software system was developed to address the specificity of the detection object; secondly, a phased array detection system based on 64 elements was constructed; finally, a region wavelet denoising method based on TFM images was proposed to solve the problem of artifacts caused by poor coupling; and based on the feature extraction method for a minimum rectangle, we analyzed the size, position, angle, and other information regarding defects. Through experiments, it has been found that this technology can effectively improve the detection efficiency of branch pipe weld defects, with a detection rate of 100%. Based on the partition fusion denoising method, the defect imaging quality can be further improved; at the same time, based on the feature extraction method, the error is 0.1 mm, the length range of various defects is 2.3 mm–6.3 mm, the width range is 0.6 mm–0.8 mm, and the angle range is 52°–75°, which can provide an application basis for the localization, classification, and risk assessment of corner weld defects in branch pipes.

Background: Periodontitis and benign prostatic hyperplasia (BPH) are all common chronic diseases with higher incidence in middle-aged and old men. Several studies have indicated a potential association between periodontitis and BPH, although the findings remain inconclusive. However, there is no mendelian randomization (MR) studies to assess this association.Methods: The 40 men who had received health check-ups were included in an epidemiological study. Genetic data of BPH (13118 cases and 72799 controls) and periodontitis (3046 cases and 195395 controls) from FinnGen project was used to perform two-sample MR analysis. The inverse-variance weighted (IVW) model was identified as the primary analytical method, with MR Egger, weighted median, simple mode, and weighted mode serving as additional approaches.Results: The epidemiological analysis demonstrated a lack of statistically significant differences in the prevalence of clinical BPH between severe periodontitis group and non-severe periodontitis group. Similarly, no statistically significant differences were found in the prevalence of severe periodontitis among individuals with clinical BPH compared to those without. Additionally, Among the five models utilized in MR analysis, including the IVW model, no evidence of a causal link between periodontitis and BPH was observed.Conclusion: The findings from our epidemiological investigation and MR analysis do not provide support for a causal relationship between periodontitis and BPH.

ObjectivesThe systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population.MethodsOur study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD.ResultsFollowing confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07–1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046).ConclusionsSII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.

Abstract Background The six‐transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan‐cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable. Aims As part of our investigation into the possible functions of STEAP3 in malignancies, we conducted a comprehensive analysis to examine the prognostic value and immune features of STEAP3 in human pan‐cancer. Methods and Results R and Cytoscape programs were applied to analyze and visualize the data. The expression of STEAP3 in both cell lines and tissues was measured utilizing a variety of approaches. Using the shRNA knockdown technique, we tested the viability of the A498 and 786‐O cell lines and validated their functions. Both CCK‐8 and transwell assays were conducted to estimate cell proliferation and invasion. The expression of STEAP3 was substantially elevated and was shown to be linked to prognosis in the majority of malignancies, notably in clear cell renal cell carcinoma (ccRCC). In addition, the expression of STEAP3 was shown to have a strong correlation with immune infiltrates, which in turn triggered the recruitment and polarization of M2 macrophages in ccRCC. The protein STEAP3 shows promise as a predictor of responses to immune‐checkpoint blockade (ICB) therapy. Positive links between STEAP3 and the epithelial‐mesenchymal transition (EMT), the p53 pathway, and the immune‐associated pathways were also found in the enrichment analysis. Our results illustrated that the STEAP3 expression level was substantially elevated in ccRCC tissues and suggested that it could stimulate EMT in ccRCC by downregulating CDH1. Conclusion In a diverse range of cancers, STEAP3 might serve as a biomarker for determining the prognosis as well as a predictor of immunotherapy responsiveness. STEAP3 is a novel biological marker for determining prognosis, and it also performs a remarkable function in the promotion of tumor growth in ccRCC by enhancing invasion and EMT, as well as by triggering the recruitment and polarization of M2 macrophages.

The characteristics of the tumour cells, as well as how tumour cells interact with their surroundings, affect the prognosis of cancer patients. The resident cells in the tumour microenvironment are mast cells (MCs), which are known for their functions in allergic responses, but their functions in the cancer milieu have been hotly contested. Several studies have revealed a link between MCs and the development of tumours. Mast cell proliferation in colorectal cancer (CRC) is correlated with angiogenesis, the number of lymph nodes to which the malignancy has spread, and patient prognosis. By releasing angiogenic factors (VEGF-A, CXCL 8, MMP-9, etc.) and lymphangiogenic factors (VEGF-C, VEGF-D, etc.) stored in granules, mast cells play a significant role in the development of CRC. On the other hand, MCs can actively encourage tumour development via pathways including the c-kit/SCF-dependent signaling cascade and histamine production. The impact of MC-derived mediators on tumour growth, the prognostic importance of MCs in patients with various stages of colorectal cancer, and crosstalk between MCs and CRC cells in the tumour microenvironment are discussed in this article. We acknowledge the need for a deeper comprehension of the function of MCs in CRC and the possibility that targeting MCs might be a useful therapeutic approach in the future.

The mechanical state of the process zone at the crack-tip is one of the main factors that affect crack initiation and growth in the long-term safe operation of oil and gas pipelines. Many tests showed that the stress and strain fields in the fracture-tip process zone can be used to define the crack propagation behavior. The goal of this paper is to improve the Hutchinson, Rice, and Rosengren (HRR) model by using cubic asymptotic polynomials to describe the stress-strain field at the crack-tip, as well as to validate the model by a thorough comparison with full-scale burst test results that account for the fracture zone's mechanical properties. The asymptotic polynomial elastic viscoplastic distribution model of stress-strain displacement field at the crack-tip is developed, and the HRR method is modified reasonably. The crack propagation test of the X80 steel pipeline in the burst test site is carried out. Experimentally, the distribution of stress and strain field in the crack-tip process zone of the X80 testing pipeline is obtained, then compared with the theoretical solution. The final results showed consistency, and the elastic viscoplastic model matched well with the running fracture test data for the X80 gas pipeline. Besides, the stress and strain fields distribution in the crack-tip process zone is verified through the full-scale test of the X80 steel pipeline, which provides a theoretical basis for the integrity evaluation of the steel pipeline.

To solve the problems of single heat source heat pump systems in severe cold regions, a dual-source hybrid heat pump unit (DSHHPU) is proposed. The mathematical models of the DSHHPU when charging R134a or its alternative refrigerants R32, R290 and R600a were established respectively, and the performance was simulated and analysed. The results showed that the four refrigerants have different performance characteristics in different aspects. In heat pipe mode, the heating capacity and evaporating pressure of R32 are 36.94% and 59.94% higher than those of R134a. The heating capacity and evaporating pressure of R290 are 5.73% and 22.99% lower than those of R134a. The heating capacity and evaporating pressure of R600a are 43.29% and 68.08% lower than those of R134a. In vapour compression heating mode, the discharge temperature of R32, R290 and R600a are 184.88, 72.98 and 66.44% of that of R134a. The coefficient of performance (COP) of R32, R290 and R600a are 72.65, 111.59 and 117.94% of that of R134a. Finally, the effects of radiation intensity and ambient temperature on key performance parameters of the different refrigerants were analysed. The research results provide a reference for research on refrigerant replacements for multi-heat source composite heat pump systems.

Complement synthesis in cells of origin is strongly linked to the pathogenesis and progression of renal disease. Multiple studies have examined local C3 synthesis in renal disease and elucidated the contribution of local cellular sources, but the contribution of infiltrating inflammatory cells remains unclear. We investigate the relationships among C3, macrophages and Th17 cells, which are involved in interstitial fibrosis. Here, we report that increased local C3 expression, mainly by monocyte/macrophages, was detected in renal biopsy specimens and was correlated with the severity of renal fibrosis (RF) and indexes of renal function. In mouse models of UUO (unilateral ureteral obstruction), we found that local C3 was constitutively expressed throughout the kidney in the interstitium, from which it was released by F4/80+macrophages. After the depletion of macrophages using clodronate, mice lacking macrophages exhibited reductions in C3 expression and renal tubulointerstitial fibrosis. Blocking C3 expression with a C3 and C3aR inhibitor provided similar protection against renal tubulointerstitial fibrosis. These protective effects were associated with reduced pro-inflammatory cytokines, renal recruitment of inflammatory cells, and the Th17 response. in vitro, recombinant C3a significantly enhanced T cell proliferation and IL-17A expression, which was mediated through phosphorylation of ERK, STAT3, and STAT5 and activation of NF-kB in T cells. More importantly, blockade of C3a by a C3aR inhibitor drastically suppressed IL-17A expression in C3a-stimulated T cells. We propose that local C3 secretion by macrophages leads to IL-17A-mediated inflammatory cell infiltration into the kidney, which further drives fibrogenic responses. Our findings suggest that inhibition of the C3a/C3aR pathway is a novel therapeutic approach for obstructive nephropathy.