APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway.

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN has been implicated in the development of multiple tumours. Herein, we determined the effect of APLN on the biological behaviour and underlying mechanisms of cervical cancer. The expression and survival curves of APLN were determined using Gene Expression Profiling Interactive Analysis. The cellular functions of APLN were detected using CCK-8, clone formation, EdU, Transwell assays, flow cytometry, and seahorse metabolic analysis. The underlying mechanisms were elucidated using gene set enrichment analysis and Western blotting. APLN was upregulated in the samples of patients with cervical cancer and is associated with poor prognosis. APLN knockdown decreased the proliferation, migration, and glycolysis of cervical cancer cells. The opposite results were observed when APLN was overexpressed. Mechanistically, we determined that APLN was critical for activating the PI3K/AKT/mTOR pathway via APLNR. APLN receptor inhibitor ML221 reversed the effect of APLN overexpression on cervical cancer cells. Treatment with LY294002, the PI3K inhibitor, drastically reversed the oncological behaviour of APLN-overexpressing C-33A cells. APLN promoted the proliferation, migration, and glycolysis of cervical cancer cells via the PI3K/AKT/mTOR pathway.

GRIM-19 deficiency promotes macrophage polarization to the M1 phenotype partly through glycolysis in unexplained recurrent spontaneous abortion†.

The occurrence of unexplained recurrent spontaneous abortion (URSA) is closely related to immune system disorders, however, the underlying mechanisms remain unclear. The purpose of this study was to investigate the expression of GRIM-19 in URSA and the possible pathogenesis of URSA according to macrophage polarization. Here, we showed that GRIM-19 was downregulated in the uterine decidual macrophages of patients with URSA and that GRIM-19 downregulation was accompanied by increased M1 macrophage polarization. Furthermore, the expression levels of glycolytic enzymes were substantially enhanced in the uterine decidual macrophages of URSA patients, and glycolysis in THP-1-derived macrophages was further enhanced by the downregulation of GRIM-19. Additionally, the increase of M1 macrophages resulting from the loss of GRIM-19 was significantly reversed in cells treated with 2-deoxy-D-glucose (2-DG, an inhibitor of glycolysis). To provide more direct evidence, GRIM-19 deficiency was shown to promote macrophage polarization to the M1 phenotype in GRIM-19+/- mouse uteri. Overall, our study provides evidence that GRIM-19 deficiency may play a role in regulating macrophage polarization in URSA, and that glycolysis may participate in this process.

Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer.

N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role in various biological processes. However, the roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated in the tumor microenvironment of cervical cancer, are still unclear. We analyzed the abnormal m6A methylation in cervical cancer, using CaSki and THP-1 cell lines, that might influence macrophage polarization and/or function in the tumor microenvironment. In addition, C57BL/6J and BALB/c nude mice were used for validation in vivo. In this study, m6A methylated RNA immunoprecipitation sequencing analysis revealed the m6A profiles in cervical cancer. Then, we discovered that the high expression of METTL14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) in cervical cancer tissues can promote the proportion of programmed cell death protein 1 (PD-1)-positive tumor-associated macrophages, which have an obstacle to devour tumor cells. Functionally, changes of METTL14 in cervical cancer inhibit the recognition and phagocytosis of macrophages to tumor cells. Mechanistically, the abnormality of METTL14 could target the glycolysis of tumors in vivo and vitro. Moreover, lactate acid produced by tumor glycolysis has an important role in the PD-1 expression of tumor-associated macrophages as a proinflammatory and immunosuppressive mediator. In this study, we revealed the effect of glycolysis regulated by METTL14 on the expression of PD-1 and phagocytosis of macrophages, which showed that METTL14 was a potential therapeutic target for treating advanced human cancers.

Could an amorphous binder Co phase improve the mechanical properties of WC-Co? A study of molecular dynamics simulation.

The trade-off effect between strength and fracture toughness typically observed in composites is challenging for the design and development of novel materials. An amorphous state can impede the trade-off effect of strength and fracture toughness, improving the mechanical properties of composites. Choosing the typical tungsten carbide-cobalt (WC-Co) cemented carbides as examples, where the amorphous binder phase was found, the impact of binder phase Co on the mechanical properties was further investigated by molecular dynamics (MD) simulations. The mechanical behavior and microstructure evolution of the WC-Co composite in the uniaxial compression and tensile processes were studied at different temperatures. The results showed that Young's modulus and ultimate compressive/tensile strengths were higher in WC-Co with amorphous Co, and the ultimate compressive/tensile strengths increased by about 11-27% compared to the samples with crystalline Co. Amorphous Co not only restricts the propagation of voids and cracks but also delays fractures. The relationship between temperatures and deformation mechanisms was also investigated, in which the tendency of strength to decrease with increasing temperature was clarified.

Development and validation of a deep learning survival model for cervical adenocarcinoma patients.

BACKGROUND: The aim was to develop a personalized survival prediction deep learning model for cervical adenocarcinoma patients and process personalized survival prediction. METHODS: A total of 2501 cervical adenocarcinoma patients from the surveillance, epidemiology and end results database and 220 patients from Qilu hospital were enrolled in this study. We created our deep learning (DL) model to manipulate the data and evaluated its performance against four other competitive models. We tried to demonstrate a new grouping system oriented by survival outcomes and process personalized survival prediction by using our DL model. RESULTS: The DL model reached 0.878 c-index and 0.09 Brier score in the test set, which was better than the other four models. In the external test set, our model achieved a 0.80 c-index and 0.13 Brier score. Thus, we developed prognosis-oriented risk grouping for patients according to risk scores computed by our DL model. Notable differences among groupings were observed. In addition, a personalized survival prediction system based on our risk-scoring grouping was developed. CONCLUSIONS: We developed a deep neural network model for cervical adenocarcinoma patients. The performance of this model proved to be superior to other models. The results of external validation supported the possibility that the model can be used in clinical work. Finally, our survival grouping and personalized prediction system provided more accurate prognostic information for patients than traditional FIGO stages.

First-principles study on the effects of N and Al doping on the mechanical properties and electronic structures of TiC.

First-principles calculations are carried out by DFT within the CASTEP plane wave code to investigate the mechanical properties and electronic structure of N and Al doped TiC. The results show that the co-doping of nitrogen and aluminum narrows the lattice constant and nitrogen could enhance the stability of TiC, however, aluminum makes the compound unstable. The calculated elastic constants and elastic moduli reveal that aluminum reduces the elastic constants, bulk modulus B, shear modulus G and Young's modulus E, but nitrogen can enhance them. The results of B/G and C 12-C 44 indicate that aluminum could significantly increase the ductility of TiC. Meanwhile, the electronic structure calculations reveal that strong p-d covalent bonds exist among C-p, N-p, Ti-d and Al-p states and Al-doping causes DOS peak transfer to a higher energy level and increases the DOS above the Fermi level. The hardness is estimated by a semi-empirical model that is based on the Mulliken overlap population and bond length. The addition of Al sharply reduces the hardness of the TiC-based alloys due to the weakest bond taking a determinative role in the hardness of materials, which is the C-Al bond in those compounds.

Electrochemical oxidation of methyl orange by a Magnéli phase Ti4O7 anode.

In this study, high quality Magnéli phase Ti4O7 bulks with electrical conductivity up to 961.5 S cm-1 were successfully prepared by spark plasma sintering (SPS) and then served as electrode materials for electrochemical oxidation of azo dye methyl orange (MO). The influences of current density and initial dye concentration on the removal rates of MO and chemical oxygen demand (COD) were studied. Removal of MO and COD exhibited an increase with increasing current density and decreasing initial concentration of MO. Complete removal of MO was realized within a short time under all experimental conditions. The removal rate of COD reached 91.7% when current density was 10 mA cm-2 and initial dye concentration was 100 mg L-1. In addition, the electrochemical oxidation rate could be described through a pseudo-first-order kinetic constant k, and the obtained experimental results could be well fitted with a proposed kinetic model in all the examined conditions. Possible degradation mechanisms for electrochemical oxidation of MO by Ti4O7 electrode were proposed on the basis of intermediate products analysis. Tests were also conducted with other commercial electrodes for comparison, including commercial graphite, stainless-steel and dimension stable anode (DSA) electrodes. The results showed that Ti4O7 anode exhibited the fastest electrochemical oxidation rates than those of the other electrodes. This study provides a feasible method for realizing high efficiency of electrochemical oxidation degradation by Ti4O7 electrode.

A gas-solid reaction growth of dense TiO2 nanowire arrays on Ti foils at ambient atmosphere.

In this paper, a facile method is demonstrated to directly fabricate dense titania nanowire arrays on titanium foils under the atmosphere without extra moist conditions. The influences of temperature, time, different catalysts, and concentrations of the respective catalysts on the growth of titania nanowires are discussed in detail. The morphology, composition and crystal structure of the titania nanostructures are revealed by scanning electron microscopy (SEM), powder-X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques, by which a gas-solid reaction mechanism is suggested to explain the growth process of TiO2 nanowires on Ti substrate.

[Effect of low molecular heparin sodium cream on the content of serum nitric oxide in random pattern skin flap: experiment with rats].

OBJECTIVE: To explore the mechanism of improvement of blood circulation in random pattern skin flap by low molecular heparin sodium cream. METHODS: 48 Wistar rats underwent formation of random skin flap of the size of 2 cm x 8 cm on the back and then were randomly divided into 2 equal groups: experiment group with low molecular heparin sodium cream smeared on the skin flaps and control group with Vaseline smeared on the skin flaps. 24, 48, and 72 hours, and 7 days after the smearing blood samples were collected from 6 rats respectively to detect the content of serum nitric oxide a (NO). Seven days after the smearing specimens were collected from the upper, middle, and lower parts of the skin flaps to undergo pathological examination. RESULTS: (1) The serum NO content of the experiment group was (53 +/- 15) micromol/L, significantly higher than that of the control group [(27 +/- 20) micromol/L, P < 0.05] 7 days after the operation. (2) The skin flap survival rate of the experiment group was (66 +/- 18)%, significantly higher than that of the control group [(22 +/- 16)%, P < 0.01]. (3) Histomorphology showed formation of neo-vessels with integrated endangium of capillary, stability of structure of mitochondria, and milder cell swelling in the flaps treated with heparin cream. CONCLUSION: Low molecular heparin sodium cream increases the content of serum NO, thus increasing the survival of skin flaps.