On optimization of Spin-Forming Process Parameters for Magnesium Alloy Wheel Hub Based on Gray Relational Analysis.

To study the influencing factors of process parameters on the wall thickness deviation and internal warpage deviation of the workpiece in magnesium alloy wheel hub spin molding, a two-pass heterogeneous spin molding model is proposed. To ensure the accuracy of the simulation results, the stress-strain data of AZ31 magnesium alloy at different temperatures and different strain rates were obtained through tests. Wall thickness deviation and internal warp deviation after molding were used as evaluation indexes of workpiece molding quality. ABAQUS software facilitated the numerical simulation and analysis of the magnesium alloy wheel hub spinning process. Gray relational degree analysis optimized the first-pass process parameters, elucidating the impact of the axial offset, the thinning ratio, and the feed ratio on forming quality. The application of optimized parameters in the hub spinning simulation resulted in a substantial 28.84% reduction in wall thickness deviation and a 4.88% reduction in inner diameter deviation. This study underscores the efficacy of employing Gray Relational Analysis for comprehensive parameter optimization, ensuring wheel hub quality. Moreover, it provides a theoretical foundation for enterprises to expedite research and development cycles and minimize associated costs.

Explore Key Genes and Mechanisms Involved in Colon Cancer Progression Based on Bioinformatics Analysis.

To explore underlying mechanisms related to the progression of colon cancer and identify hub genes associated with the prognosis of patients with colon cancer. GSE10950 and GSE62932 were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was utilized to screen out the differentially expressed genes (DEGs). Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted on DEGs. Moreover, STRING and Cytoscape software were utilized for establishing the network of protein-protein interaction (PPI) and identifying hub genes. Afterward, data from The Cancer Genome Atlas (TCGA) was utilized for identifying prognosis-related hub genes by Kaplan-Meier survival analysis. Colon cancer cell line LOVO and human normal intestinal epithelial cell line NCM-460 were exploited to demonstrate the differential expression of selected hub genes through RT-qPCR and western blot. The LOVO cells were transfected to regulate expressions of prognosis-associated genes, followed by exploring the effects of those genes on prognosis by Cell Counting Kit-8 assay and colony-forming assay for cancer cell proliferation, cell scratch test and transwell migration assay for cancer cell migration and Annexin V-PE/7-AAD double staining as well as flow cytometry for cancer cell apoptosis. In this study, 266 common DEGs were obtained from the intersection of two datasets. The GO analysis suggested the common DEGs mainly participated in the one-carbon metabolic process, cell cycle G2/M phase transition, organelle fission, cell cycle phase transition regulation, and regulation of mitotic cell cycle phase transition. The KEGG analysis demonstrated the common DEGs were related to the p53 signaling pathway, nitrogen metabolism, mineral absorption, and cell cycle. 10 hub genes including CCNB1, KIF4A, TPX2, MT1F, PRC1, PLK4, CALD1, MMP9, CLCA1, and MMP1 were identified and CCNB1, CLCA1, and PLK4 were prognosis-related. Increased expression of CCNB1, CLCA1, and PLK4 restrained proliferation as well as migration of cancer cells and induced apoptosis of cancer cells. CCNB1, KIF4A, TPX2, MT1F, PRC1, PLK4, CALD1, MMP9, CLCA1, and MMP1 were identified as hub genes and CCNB1, CLCA1, and PLK4 could inhibit the progression of colon cancer through inhibiting proliferation as well as migration of the cancer cell and promoting apoptosis of cancer cell.

Raptinal ameliorates 1,2-dimethylhydrazine-induced colon cancer through p53/Bcl2/Bax/caspase-3-mediated apoptotic events in vitro and in vivo.

OBJECTIVES: Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems. MATERIALS AND METHODS: The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis. RESULTS: The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation. CONCLUSIONS: These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.

A novel natural killer cell-related signatures to predict prognosis and chemotherapy response of pancreatic cancer patients.

Background: Natural killer (NK) cells are involved in monitoring and eliminating cancers. The purpose of this study was to develop a NK cell-related genes (NKGs) in pancreatic cancer (PC) and establish a novel prognostic signature for PC patients. Methods: Omic data were downloaded from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and used to generate NKG-based molecular subtypes and construct a prognostic signature of PC. NKGs were downloaded from the ImmPort database. The differences in prognosis, immunotherapy response, and drug sensitivity among subtypes were compared. 12 programmed cell death (PCD) patterns were acquired from previous study. A decision tree and nomogram model were constructed for the prognostic prediction of PC. Results: Thirty-two prognostic NKGs were identified in PC patients, and were used to generate three clusters with distinct characteristics. PCD patterns were more likely to occur at C1 or C3. Four prognostic DEGs, including MET, EMP1, MYEOV, and NGFR, were found among the clusters and applied to construct a risk signature in TCGA dataset, which was successfully validated in PACA-CA and GSE57495 cohorts. The four gene expressions were negatively correlated with methylation level. PC patients were divided into high and low risk groups, which exerts significantly different prognosis, clinicopathological features, immune infiltration, immunotherapy response and drug sensitivity. Age, N stage, and the risk signature were identified as independent factors of PC prognosis. Low group was more easily to happened on PCD. A decision tree and nomogram model were successfully built for the prognosis prediction of PC patients. ROC curves and DCA curves demonstrated the favorable and robust predictive capability of the nomogram model. Conclusion: We characterized NKGs-derived molecular subtypes of PC patients, and established favorable prognostic models for the prediction of PC prognosis, which may serve as a potential tool for prognosis prediction and making personalized treatment in PC.

Investigation of Yield Surfaces Evolution for Polycrystalline Aluminum after Pre-Cyclic Loading by Experiment and Crystal Plasticity Simulation.

This study aims at introducing the back stress of anisotropic strain-hardening into the crystal plasticity theory and demonstrating the rationality of this crystal plasticity model to describe the evolution of the subsequent yield surface of polycrystalline aluminum at the mesoscopic scale under complex pre-cyclic loading paths. By using two different scale finite element models, namely a global finite element model (GFEM) as the same size of the thin-walled tube specimen used in the experiments and a 3D cubic polycrystalline aggregate representative volume element (RVE) model, the evolution of the subsequent yield surface for different unloading cases after 30 pre-cycles is further performed by experiments and numerical simulations within a crystal plasticity finite element (CPFE) frame. Results show that the size and shape of the subsequent yield surfaces are extremely sensitive to the chosen offset strain and the pre-cyclic loading direction, which present pronounced anisotropic hardening through a translation and a distortion of the yield surface characterized by the obvious "sharp corner" in the pre-deformation direction and "flat" in the reverse direction by the definition of small offset strain, while the subsequent yield surface exhibits isotropic hardening reflected by the von Mises circle to be distorted into an ellipse by the definition of large offset strain. In addition, the heterogeneous properties of equivalent plastic strain increment are further discussed under different offset strain conditions. Modeling results from this study show that the heterogeneity of plastic deformation decreases as a law of fraction exponential function with the increasing offset strain. The above analysis indicates that anisotropic hardening of the yield surface is correlated with heterogeneous deformation caused by crystal microstructure and crystal slip. The crystal plasticity model based on the above microscopic mechanism can accurately capture the directional hardening features of the yield surface.

Statistical Analysis of Grain-Scale Effects of Twinning Deformation for Magnesium Alloys under Cyclic Strain Loading.

To reveal the relationship between grain size and twinning deformation of magnesium alloys under cyclic strain, this study carried out a group of strain-controlled low-cycle fatigue experiments and statistical analysis of microstructures. Experimental results show that the shape of the hysteresis loop exhibits significant asymmetry at different strain amplitudes, and the accumulation of residual twins plays an important role in subsequent cyclic deformation. For the different strain amplitudes, the statistical distribution of the grain size of magnesium alloy approximately follows the Weibull probability function distribution, while the statistical distribution of twin thickness is closer to that of Gaussian probability function. The twin nucleation number (TNN) increases with the increase of grain size, but there is no obvious function relationship between twin thickness and grain size. Twin volume fraction (TVF) increases with the increase of grain size, which is mainly due to the increase of TNN. This work can provide experimental evidence for a more accurate description of the twinning deformation mechanism.

Plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2.

Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation. However, the bone-related function of plastin 1, another family member of plastins, has not been assessed. In this study, we addressed the functional importance of plastin 1 in osteoblasts. We characterized the expression patterns of plastin 1 during osteoblast differentiation and revealed its important role in this process. In both HEK 293T and hFOB1.19 cells, plastin 1 was demonstrated to regulate intracellular Ca2+. Accordingly, we revealed that higher Ca2+ concentration promotes osteoblast differentiation. Finally, we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency. Together, our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+. Our work sheds new light on the role played by plastins in bone homeostasis.

TIPE1 Promotes Cervical Cancer Cell Chemoresistance to Cisplatin in a Wild-Type p53-Dependent Manner.

Previous studies have revealed that TIPE1 serves as a tumor suppressor gene in several tumor types. However, we demonstrated that TIPE1 can promote cervical cancer proliferation by suppressing p53 activity. Here, we showed that TIPE1 inhibits cervical cancer cell apoptosis both in vivo and in vitro. Mechanistically, we revealed that TIPE1 facilitates chemoresistance in a wild-type p53-dependent manner. The results indicated that TIPE1 is responsible for the transition from chemosensitivity to chemoresistance, and that it can serve as a promising target in cervical cancer chemotherapy.

Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis.

BACKGROUND: Recent studies have shown that T cell-mediated cellular immune mechanisms play important roles in the progression of hepatitis B to liver cirrhosis, but the underlying mechanisms remain unclear. This present study was aimed to determine the relationship between Treg/Th17 and hepatitis B-associated liver cirrhosis. METHODS: The Treg and Th17 cell frequencies in the peripheral blood of all participants, including 93 patients with hepatitis B-associated liver cirrhosis and 40 healthy subjects, were measured by flow cytometer. Cox regression model and receiver operating characteristic(ROC) curves were applied to investigate the prognostic significance of Treg/Th17 ratio in decompensated liver cirrhosis. RESULTS: We observed the Treg/Th17 imbalance was present in patients with hepatitis B-associated liver cirrhosis, with reduced Treg cells in their peripheral blood, increased Th17 cells and decreased Treg/Th17 ratio. Treg and Th17 cells were negatively correlated. Treg/Th17 imbalance was closely related to the clinical stage of hepatitis B-associated liver cirrhosis. The Virus load, Treg frequencies and the Treg/Th17 ratio were independent factors predicting decompensated liver cirrhosis from a Cox regression model. The ROC analysis showed that the Treg/Th17 ratio was the best marker for predicting decompensated liver cirrhosis. CONCLUSIONS: Treg/Th17 imbalance is involved in the pathogenesis of hepatitis B-associated liver cirrhosis and the Treg/Th17 ratio can be used as a potential marker for predicting decompensated liver cirrhosis.

Change in the Treg/Th17 cell imbalance in hepatocellular carcinoma patients and its clinical value.

Recent studies have indicated that the T cell mediated immune response plays an important role in the pathogenesis of hepatitis B virus-associated hepatocellular carcinoma (HCC), but the underlying mechanism remains unclear. In this study, we found an imbalance in Treg/Th17 cells in peripheral blood mononuclear cells from HCC patients. The percentages of CD4CD25FOXP3 Treg cells and CD4IL-17 Th17 cells were significantly higher in HCC patients than in the controls. The numbers of Treg and Th17 cells were increased and correlated in a positive linear manner. Moreover, the increased percentages of Treg and Th17 cells were closely related to the tumor stage and tumor size of HCC. Therefore, we concluded that Treg and Th17 cells might participate in the promotion of the invasion and progression of HCC and that a Treg/Th17 cell imbalance might be able to serve as an important indicator for determining the progression and prognosis of HCC. Further studies might provide novel therapeutic targets for HCC.