Influence of Cyclic Heat Treatment Temperature on Microstructure and Mechanical Properties of 18Ni(C250) Maraging Steel.

Cyclic heat treatment is an effective approach for enhancing the mechanical properties of 18Ni(C250) maraging steel, and the selection of cyclic heat treatment temperature is a key factor. In this study, a cyclic heat treatment process with a two-step solution treatment is employed to investigate the influence of cyclic heat treatment temperature, specifically the first solution treatment temperature (920 °C, 950 °C, and 980 °C), on the microstructure and mechanical properties of 18Ni(C250) maraging steel. The results indicate that with an increase in the cyclic heat treatment temperature, the average grain size of the 18Ni(C250) maraging steel decreases initially and then increases. When the cyclic heat treatment temperature reaches 950 °C, the grain size is at its minimum, exhibiting optimal grain uniformity. Additionally, the increase in cyclic heat treatment temperature results in a reduction in the size of martensitic lath with the same orientation inside the grains, along with an increase in the relative quantity of low-angle grain boundaries. Furthermore, the volume fraction and size of retained austenite show a monotonous increase with the rise in the temperature of the cyclic heat treatment, and the rate of increase becomes notably larger when the temperature is raised from 950 °C to 980 °C. Based on the observed microstructural changes, the variation in the mechanical properties of the 18Ni(C250) maraging steel was analyzed. Specifically, as the cyclic heat treatment temperature increases, the tensile strength of the 18Ni(C250) maraging steel initially increases and then stabilizes, while the elongation and fracture toughness exhibit a monotonic increase.

S100A4/NF-κB axis mediates the anticancer effect of epigallocatechin-3-gallate in platinum-resistant ovarian cancer.

Resistance to cisplatin (cis-dichlorodiamineplatinum, DDP) in ovarian cancer is a significant clinical challenge. Epigallocatechin-3-gallate (EGCG) has shown promise in cancer therapy. However, its effects on DDP-resistant ovarian cancer remain understudied. This study aims to assess the impact of EGCG on DDP-resistant cells and elucidate the associated molecular mechanisms. DDP-resistant cell lines were utilized for biological characterization. EGCG effectively inhibited proliferation, mobility, and induced apoptosis in OC/DDP cells. It downregulated the expression of S100A4 and NF-κB while upregulating p53 expression. These effects were reversed upon overexpression of S100A4 or NF-κB. In vivo experiments confirmed tumor inhibition and KI67 inhibition by EGCG. Moreover, EGCG downregulated the expression of S100A4 and NF-κB while upregulating p53 in xenograft mice compared to those without EGCG treatment. This study suggests that EGCG suppresses cancer progression through the S100A4/NF-κB signaling pathway, involving interaction with p53. EGCG holds potential as an anticancer candidate for OC/DDP.

The severity of postoperative complications after robotic versus laparoscopic surgery for rectal cancer: A systematic review, meta-analysis and meta-regression.

OBJECTIVE: Robotic surgery (RS) has been increasingly used for the resection of rectal cancer, and its advantages over laparoscopic surgery (LS) have been demonstrated. However, few studies focused on the severity of postoperative complications. This study aimed to compared the postoperative complications within 30 days after RS over LS according to the Clavien-Dindo (C-D) classification. METHODS: A literature research of PubMed, Embase, Cochrane Library and Web of Science were systematically performed. The studies comparing the complications of RS and LS for rectal cancer based on the C-D classification were enrolled. Primary outcomes were C-D grade III, IV, V, III-V (severe complications). RESULTS: Seventeen studies (3193 patients) were included in the final analysis: 1554 underwent RS and 1639 underwent LS. The RS group was associated with significantly lower rates of severe complications (OR = 0.69, 95% CI 0.53-0.90, P = 0.005), C-D grade IV (OR = 0.69, 95% CI 0.53-0.90, P = 0.005), and anastomotic leak (OR = 0.66, 95% CI 0.48-0.91, P = 0.01). There was no significant difference in C-D grade III, C-D grade I, II, I-II (minor complications), overall complications, bleeding, wound complications, postoperative ileus, urinary retention, readmission, reoperation between two groups. CONCLUSIONS: Robotic surgery is safe for rectal cancer and may be an effective alternative to laparoscopic surgery, with lower rates of severe complications, C-D grade IV, and anastomotic leak. Further large randomized controlled trials are necessary to confirm this conclusion.

Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells.

One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout. It was discovered that the MPC1 gene knockout cells revealed a metabolism reprogramming to aerobic glycolysis with reduced ATP production, and the cells became more migratory and resistant to both chemotherapy and radiotherapy. In addition, the MPC1 knockout cells expressed significantly higher levels of the stemness markers Nanog, Hif1α, Notch1, CD44 and ALDH. To further verify the correlation of MPC gene function and cell stemness/metabolic reprogramming, MPC inhibitor UK5099 was applied in two ovarian cancer cell lines and similar results were obtained. Taken together, our results reveal that functional MPC may determine the fate of metabolic program and the stemness status of cancer cells in vitro.

MPC1 and MPC2 expressions are associated with favorable clinical outcomes in prostate cancer.

BACKGROUND: Cancer cells exhibit an altered metabolism, which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role by transporting pyruvate into mitochondrial through the mitochondrial inner membrane. Therefore, their protein expression in cancers may be of clinical consequences. There are studies showing low levels of MPC1 expression in colon, kidney and lung cancers, and the expression of MPC1 correlates with poor prognosis. However, the expression status of MPC1 and MPC2 in prostate cancer (PCA) is unclear. METHODS: In this study, expression of MPC1 and MPC2 in LNCaP and DU145 prostate cancer cell lines was examined by immunocytochemistry (ICC) and Western blotting. Compared to the LNCaP cells, lower levels of MPC1 and MPC2 expression in the DU145 cell line was identified. We then extended our study to 88 patients with prostate cancer who underwent transurethral electro-vaporization of prostate or radical prostatectomy at the First Affiliated Hospital of Zhengzhou University, Henan, China. Patient-derived paraffin embedded PCA specimens were collected for immunohistochemistry (IHC). Correlations with clinicopathologic factors were evaluated by Chi-square or Fisher´s exact probability tests. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. The Cox proportional hazard regression model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis. RESULTS: Linear regression analysis revealed that MPC1 expression level was positively correlated with MPC2 expression (r = 0.375, P = 0.006) in the prostate cancers. MPC1 expression was negatively associated with UICC stage (P = 0.031). While UICC stage (P < 0.001) and lymph node metastasis (P = 0.002) were negatively associated with MPC2 expression. Positive MPC1 or MPC2 expression in cancer tissues was significantly associated with higher OS (P < 0.05). The multivariate analysis showed that both MPC1 and MPC2 expressions in PCA were independent prognostic factors for higher OS (For MPC1: RR = 0.654, 95% CI: 0.621-0690, P < 0.001; For MPC2: RR = 0.696, 95% CI: 0.660-0.734, P < 0.001). CONCLUSIONS: Our study indicates that MPC1 and MPC2 expressions are of prognostic values in PCAs and that positive expression of MPC1 or MPC2 is a predictor of favorable outcome.

Establishment of mitochondrial pyruvate carrier 1 (MPC1) gene knockout mice with preliminary gene function analyses.

Pyruvate plays a critical role in the mitochondrial tricarboxylic acid (TCA) cycle, and it is the center product for the synthesis of amino acids, carbohydrates and fatty acids. Pyruvate transported across the inner mitochondrial membrane appears to be essential in anabolic and catabolic intermediary metabolism. The mitochondrial pyruvate carrier (MPC) mounted in the inner membrane of mitochondria serves as the channel to facilitate pyruvate permeating. In mammals, the MPC is formed by two paralogous subunits, MPC1 and MPC2. It is known that complete ablation of MPC2 in mice causes death on the 11th or 12th day of the embryonic period. However, MPC1 deletion and the knowledge of gene function in vivo are lacking. Using the new technology of gene manipulation known as Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 (CRISPR/Cas9) systems, we gained stable MPC1 gene heterozygous mutation mice models, and the heterozygous mutations could be stably maintained in their offsprings. Only one line with homozygous 27 bases deletion in the first exon was established, but no offsprings could be obtained after four months of mating experiments, indicating infertility of the mice with such homozygous deletion. The other line of MPC1 knockout (KO) mice was only heterozygous, which mutated in the first exon with a terminator shortly afterwards. These two lines of MPC1 KO mice showed lower fertility and significantly higher bodyweight in the females. We concluded that heterozygous MPC1 KO weakens fertility and influences the metabolism of glucose and fatty acid and bodyweight in mice.