Laser shock polishing reduces surface roughness and enhances material performance by utilizing the mechanical effect of shock wave generated through high-power-density laser irradiation. However, the deformation behavior of surface material during laser shock polishing and the propagation characteristic of induced stress wave remain insufficiently understood. This study developed a finite element analysis model incorporating the microtopography of milled specimens and experimentally validated its reliability. Using this verified model, the deformation behavior of 2024-T351 aluminum alloy under both initial and subsequent laser shock was investigated, as well as the associated stress wave propagation feature. The findings reveal that the surface deformation under single-pulse laser shock loading can be divided into three stages, corresponding to the deformation time intervals of 0-400 ns, 400-550 ns, and 550-1200 ns, respectively. Correspondingly, the specimen surface profile undergoes characteristic transformations across these deformation stages. Numerical simulations explore that the wave velocities of elastic waves and plastic waves in the aluminum alloy specimen are 5625.7 m/s and 5001.6 m/s respectively, demonstrating close agreement with the theoretical calculation results. In addition, the wave amplitude exhibits exponential attenuation as a function of depth. After laser shock polishing, the dominant factors governing surface profile characteristics shift from milling conditions to laser shock processing parameters. This transition is attributed to the velocity gradient between surface peaks and valleys, and the deformation coordination effect induced by the contact foil.

Fracture is one of the most common defects encountered in laser shock forming of thin foils. In this study, the fracture mechanisms of copper foils during laser shock bulging were investigated experimentally and numerically under different ratios of laser beam diameter (d) to die cavity diameter (D). The failure locations, surface morphologies, and fracture modes predicted by simulation are in good agreement with the experimental results. Three distinct fracture modes were identified: a tensile fracture mode occurring near the loading edge, driven by tensile stress at d/D = 0.5; a shear fracture mode at the die fillet, induced by shear stress at d/D = 1.25; and a mixed tensile-shear fracture mode developing at both the loading edge and the die fillet, caused by combined tensile and shear stresses at d/D = 0.75. Further analyses of the stress, strain, and thickness distributions reveal that fracture initiates in regions exhibiting severe thickness reduction resulting from intense stress concentration. Among the three modes, the shear failure mode exhibited the smallest bulging depth and thickness reduction ratio, indicating that a large d/D ratio or an excessively high forming velocity is unfavorable in laser shock bulging.

Point to the manufacturing process of variable-section rectangular tube, a four-die radial extrusion process was designed in this article. The general deformation law was researched in two-dimensions, the influence of deformation parameters on the deformation results was explored, and the method by using the mold anti-deformation to eliminate the concave defects was proposed. For the tube parts with common thickness to diameter ratio, the corresponding optimal die arc degree is obtained through simulation and optimization. After that, the two-dimensional deformation law is applied to three dimensions, and the methods to eliminate the defect are carefully studied and successfully realized. Taking a variable-section rectangular tube as an example, the experiment was carried out. The experimental results were compared with the simulation results, and the accuracy of the simulation results and the feasibility of the process were verified.

Prostate cancer is the most prevalent cancer among men worldwide and exhibits significant genetic heritability. In this study, we performed an integrative analysis combining chromatin accessibility profiling, transcriptomics, and two-stage case-control studies, alongside an unbiased phenome-wide exploration in the FinnGen cohort. This comprehensive approach identified the enhancer-associated SNP rs7077830 at chromosome 10q11 as a critical modulator of prostate cancer susceptibility. Mechanistic investigations revealed that rs7077830 exerted allele-specific enhancer activity, driving NCOA4 expression via a ZNF384-mediated enhancer-promoter interaction. CRISPR/Cas9-mediated single-nucleotide editing confirmed the direct regulatory role of rs7077830 on NCOA4 and its contribution to prostate cancer progression. Functional studies demonstrated that NCOA4 acted as a tumor suppressor by promoting ferroptosis. Furthermore, NCOA4 expression modulated sensitivity to ferroptosis-inducing agents. Strikingly, rs7077830 genotypes were directly linked to ferroptosis status in prostate cancer. These findings highlight the role of noncoding genetic variants in prostate cancer pathogenesis, provide insights into enhancer-driven ferroptosis regulation, and suggest a promising therapeutic avenue for patients with prostate cancer carrying specific rs7077830 genotypes.Significance: An enhancer mechanism mediated by a noncoding variant drives prostate cancer risk by regulating tumor suppressor expression and ferroptosis while conferring susceptibility to the potential of genotype-based precision therapeutic approaches.

Enhancer RNAs (eRNAs), a subclass of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression; however, their functional roles in prostate cancer remain largely unexplored. In this study, we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues. By incorporating chromatin immunoprecipitation sequencing data, we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways. Among these, lactotransferrin-eRNA (LTFe) was markedly downregulated in prostate cancer tissues, with functional analyses revealing its tumor-suppressive role. Mechanistically, LTFe promotes the transcription of its target gene, lactotransferrin (LTF), by interacting with heterogeneous nuclear ribonucleoprotein F (HNRNPF) and facilitating enhancer-promoter chromatin interactions. Furthermore, we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport. Notably, androgen receptor (AR) signaling disrupts LTFe-associated chromatin looping, leading to ferroptosis resistance. Therapeutically, co- administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth, offering a promising strategy for castration-resistant prostate cancer. Collectively, this study provides novel insights into the mechanistic role of eRNAs in prostate cancer, highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.

Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, the challenges of low response rates and prevalent drug resistance underscore the imperative for a deeper understanding of the tumor microenvironment (TME) and the pursuit of novel targets. Recent findings have revealed the profound impacts of biomechanical forces within the tumor microenvironment on immune surveillance and tumor progression in both murine models and clinical settings. Furthermore, the pharmacological or genetic manipulation of mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, and TRPV4, has shown remarkable potential in immune activation and eradication of tumors. In this review, we delved into the underlying biomechanical mechanisms and the resulting intricate biological meaning in the TME, focusing mainly on the extracellular matrix, the stiffness of cancer cells, and immune synapses. We also summarized the methodologies employed for biomechanical research and the potential clinical translation derived from current evidence. This comprehensive review of biomechanics will enhance the understanding of the functional role of biomechanical forces and provide basic knowledge for the discovery of novel therapeutic targets.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma, and the tumour growth and metastasis of ccRCC are related to prognosis. N4-acetylcytidine (ac4C) is one of the major modifications of RNA and is known to be mediated by N-acetyltransferase 10 (NAT10). The role of NAT10 in cancer is gradually being revealed, although the role of NAT10-mediated RNA ac4C modification in ccRCC has not been reported. In this study, NAT10 was found to be upregulated in ccRCC tissues and associated with a poor prognosis in patients. HIF-1α activated NAT10 expression at the transcriptional level. CCK8, EdU, Transwell and scratch assays after NAT10 knockdown or overexpression showed that NAT10 promoted cell proliferation and migration. The results of subcutaneous xenograft and caudal vein injection showed that NAT10 promoted tumour growth and metastasis in vivo, while Remodelin inhibited tumour growth. The acRIP-seq, RIP, RNA stability and dual luciferase reporter experiments showed that NAT10 activated ac4C acetylation of NFE2L3 mRNA and promoted NFE2L3 mRNA stability. The ChIP-seq results showed that NFE2L3 regulated the expression of LASP1 and thus activated the AKT/GSK3β signalling pathway. In summary, our results suggest that NAT10 mediates ac4C acetylation of NFE2L3 mRNA, promotes its mRNA stability, regulates the LASP1-AKT/GSK3β/β-catenin axis and promotes the progression of renal clear cell carcinoma.

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5 +/- 10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7 +/- 12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions:68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC

OBJECTIVE:To investigate preoperative predictors for selecting different surgical approaches in patients with renal cell carcinoma with inferior vena cava (IVC) tumor thrombus (RCC-IVCTT), and to establish and validate corresponding predictive models. METHODS:Clinical data of 583 RCC-IVCTT patients were retrospectively analyzed. Of these, 465 cases were used to construct predictive models, and 118 cases were used for validation. Univariate and multivariate analyses identified independent predictors for surgical strategies. Two nomogram prediction models were established based on relevant independent factors to predict surgical approach. RESULTS:In the development cohort, 342 patients underwent IVC thrombectomy (IVCT), 91 underwent IVC cavectomy (IVCC), and 32 underwent IVC reconstruction (IVCR). Multivariate logistic regression analysis identified the following predictors for inability to perform IVCT: higher Mayo classification of tumor thrombus (TT), IVC wall invasion, presence of bland thrombus, pan-immune-inflammation value (PIV) > 358 × 109, and maximum anteroposterior (AP) diameter of IVC at renal vein ostium (RVo) > 24 mm. Platelet >170 × 109/L and inadequate collateral circulation were predictors for IVCR. The developed model predicted capacity of the nomogram was evaluated in terms of its calibration, discrimination, and clinical utility. The validation set confirmed these findings. CONCLUSION:The comprehensive preoperative predictive model for RCC-IVCTT patients aids in preoperative determination of the required surgical approach and necessity for IVC angiography, facilitating perioperative preparation and reducing unnecessary invasive examinations.

Abstract In order to improve the surface quality of incremental forming parts, this paper is studied. Through numerical simulation, the influence rules of different overlapping materials and overlapping thickness on the forming quality of target parts are obtained, and the optimal forming process parameters are given. Compared with the experimental results, the better forming results were obtained.

Aiming at the bending process of ordinary rectangular tube, the influence of parameters such as friction coefficient, corner radius of tube blank, and rotational speed of bending die on the bending defects was studied. The traditional rotary bending process was improved and proposed the non-mandrel anticompensation process. For the variable-section rectangular tube, a variable-radius bending die was designed. For a certain size of variable-section rectangular tube, the anti-compensation parameters of each part were optimized. Take the minimum of internal folding and external depression as the optimization goal, the influence law of different parameters was obtained, and two sets of optimization parameters were obtained. Then, the two sets of parameters were analyzed using the comprehensive equilibrium method. Finally, a set of optimal process parameters was obtained.

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein–protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53 , TTN , and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors ( P = 0.020). NAC significantly decreased the mutation rate ( P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3 ) and a deleted region at 3p13 (harboring FOXP1 ) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers ( CDKAL1 P409L , ADGRA2 and ADRB3 ) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

Prostate cancer (PCa) is one of the most common malignant tumors affecting the male genitourinary system. However, there is currently a lack of effective treatments for patients with advanced prostate cancer, which significantly impacts men’s overall health. Exonuclease 1 (EXO1), a protein with mismatch repair and recombination functions, has been found to play a vital role in various diseases. In our study, we discovered that EXO1 acts as a novel biomarker of PCa, which promotes prostate cancer progression by regulating lipid metabolism reprogramming in prostate cancer cells. Mechanistically, EXO1 promotes the expression of SREBP1 by inhibiting the P53 signaling pathway. In summary, our findings suggest that EXO1 regulated intracellular lipid reprogramming through the P53/SREBP1 axis, thus promoting PCa progression. The result could potentially lead to new insights and therapeutic targets for diagnosing and treating PCa.

In this study, we present a new three-stage forming and two-stage heating forming process to improve the forming quality of tubing end upsetting. The forming process of the new process is studied by numerical simulation, and the best forming process parameters are obtained. The experimental device is designed, and the experimental results verify the accuracy of the simulation results. Through this process, the quality of the transition zone can be guaranteed while the concave defects of the inner wall can be eliminated, which has certain guiding significance for the actual production.

Breast cancer is the most commonly diagnosed cancer in women globally and a leading cause of cancer-related mortality. However, current detection methods, such as X-rays, ultrasound, CT scans, MRI, and mammography, have their limitations. Recently, with the advancements in precision medicine and technologies like artificial intelligence, liquid biopsy, specifically utilizing Surface-Enhanced Raman Spectroscopy (SERS), has emerged as a promising approach to detect breast cancer. Liquid biopsy, as a minimally invasive technique, can provide a temporal reflection of breast cancer occurrence and progression, along with a spatial representation of overall tumor information. SERS has been extensively employed for biomarker detection, owing to its numerous advantages such as high sensitivity, minimal sample requirements, strong multi-detection ability, and controllable background interference. This paper presents a comprehensive review of the latest research on the application of SERS in the detection of breast cancer biomarkers, including exosomes, circulating tumor cells (CTCs), miRNA, proteins and others. The aim of this review is to provide valuable insights into the potential of SERS technology for early breast cancer diagnosis.

To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2–3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2–3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2–3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2–3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. ChiCTR2200056091

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.

The rise and development of electric vehicles have brought much attention to the recycling of lithium-ion batteries (LIBs). However, the recovery of critical metals from LiNixCoyMn1_x_ yO2 (NCM) is a challenge, especially for the nickel and cobalt, which have similar chemical properties. Here, a novel ternary deep eutectic solvent (DES) composed of choline chloride, ethylene glycol, and tartaric acid was proposed. Our protocol of DES synthesis, nickel separation, and leaching of cobalt and manganese were integrated into one step, which significantly simplified the recovery process. The crystallization occurring during DES leaching was subjected to detailed investigation. The lithium, nickel, and cobalt were sequentially separated as Li2CO3, NiO, and Co(OH)2 by anterior formic acid leaching and posterior electrodeposition. After electrodeposition, DES was reused. This work provides new ideas for the sequential separation of critical metals from NCM and has great application prospects.

Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2’s biological significance in pan-cancer, notably in prostate cancer (PCa). PDIA2 expression is elevated in various tumors and closely related to patient prognosis. Patients with prostate cancer who express PDIA2 high in particular have a bad prognosis in terms of progression-free survival. In addition, the upregulation of PDIA2 expression in prostate cancer patients is accompanied by higher Gleason scores, advanced tumor staging, lymph node metastasis, and elevated PSA levels. Detailed experiments further demonstrate that PDIA2 is a carcinogenic gene affecting prostate cancer cells’ response to dasatinib therapy. For patients with prostate cancer, there is a clear positive connection between the expression level of PDIA2 and a bad prognosis. The prostate cancer treatment efficacy of dasatinib is hampered by PDIA2, which is intimately linked to the growth, invasion, and metastasis of PCa cells. In summary, our research highlights the potential of PDIA2 as a biomarker for the diagnosis and management of PCa.