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Abstract Background Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. In the current study, we determined the relevant players and role of N 6 -methyladenine (m6A) RNA methylation in cervical cancer progression. Methods The roles of m6A RNA methylation and centromere protein K (CENPK) in cervical cancer were analyzed using bioinformatics analysis. Methylated RNA immunoprecipitation was adopted to detect m6A modification of CENPK mRNA. Human cervical cancer clinical samples, cell lines, and xenografts were used for analyzing gene expression and function. Immunofluorescence staining and the tumorsphere formation, clonogenic, MTT, and EdU assays were performed to determine cell stemness, chemoresistance, migration, invasion, and proliferation in HeLa and SiHa cells, respectively. Western blot analysis, co-immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter, cycloheximide chase, and cell fractionation assays were performed to elucidate the underlying mechanism. Results Bioinformatics analysis of public cancer datasets revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of CENPK mRNA. CENPK expression was elevated in cervical cancer, associated with cancer recurrence, and independently predicts poor patient prognosis [hazard ratio = 1.413, 95% confidence interval = 1.078 − 1.853, P = 0.012]. Silencing of CENPK prolonged the overall survival time of cervical cancer-bearing mice and improved the response of cervical cancer tumors to chemotherapy in vivo (P

Abstract Background This study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. Methods The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan–Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells. Results Compared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues (P

雙語教育所欲培養的雙語能力常被認為是跨文化溝通的基礎，而教育部在其「中小學國際教育白皮書2.0」將雙語課程納入臺灣國際教育的架構中，著眼的正是基本語言溝通能力之養成。然而，本文的立論基礎在於雙語教育是否能協助學生培養跨文化素養所需之溝通能力，必須正視雙語教育處在哪個階段。因此，本文首先對臺灣雙語教育政策的發展進行梳理，並說明其在學校體系中推動時所面對的挑戰；其次剖析臺灣目前的雙語教育能量與培養跨文化溝通目標間的距離；文末提出 雙語教育的發展應奠基在現場的真實狀況，將腳步站穩並發展跨文化溝通能力之後，未來才有可能變成跨文化素養之助力。 The language proficiency fostered by the promotion of Bilingual education is often considered as the foundation of intercultural communication. In the White Paper on International Education in Primary and Junior High Schools 2.0, the bilingual curriculum is part of the structure of international education in Taiwan because language is essential for intercultural communication. However, the argument of this paper is on whether bilingual education is a pushing force to advance intercultural communication relying on the developmental stage that bilingual education is in. This paper starts by mapping out the context of bilingual education and the challenges it faces in the Taiwanese school system. Then, the gap between current bilingual education and intercultural competence is explicated. At the end of this paper, it is suggested that bilingual education has to be rooted in the Taiwanese school system well first to cultivate intercultural communication capacity so that it could be the foundation of intercultural competence.

Different oil well tubes have different influences on CO2 corrosion.In order to optimize the materials with the best corrosion resistance to CO2, it is necessary to explore the corrosion of materials of conventional oil well tubes under different conditions.Therefore, taking the production well of CO2 composite flooding injection in Block nine six of Karamay oilfield as the research object, and simulating the actual service condition of oil well pipes, the corrosion weight loss experiments on N80, 3Cr, tungsten-plated heat insulation tube and P110 oil tube materials were carried out.The Potentiodynamic polarization curve and electrochemical impedance spectroscopy(EIS)were measured by three electrode system, scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS)and X-ray diffraction(XRD)were used to observe the microstructure of corrosion products.Results showed that the corrosion rate of the four kinds of materials increased first and then decreased with the increase of temperature.With the increase of pressure, the corrosion rate of the four kinds of casing steels increased.The corrosion rate of tungsten-plated heat insulation tube and 3Cr was obviously lower than that of N80 and P110.According to the corrosion morphology, the four kinds of casing steels were corroded in varying degrees.The serious corrosion occurred on the surface of N80 and P110 whereas slight corrosion occurred on the surface of the tungsten-plated heat insulation tube and the 3Cr.Therefore, the corrosion law of four oil well tubes in CO2-driven environment was obtained, the suggestions on the design and selection of oil well tubes in CO2-driven environment were proposed to select the materials with the best corrosion resistance to CO2 optimally.

Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5. [ABSTRACT FROM AUTHOR]

Automatic identification system (AIS) data record a ship’s position, speed over ground (SOG), course over ground (COG), and other behavioral attributes at specific time intervals during a ship’s voyage. At present, there are few studies in the literature on ship trajectory classification, especially the clustering of trajectory segments, to measure the multi-dimensional information of trajectories. Therefore, it is necessary to fully utilize the multi-dimensional information from AIS data when utilizing ship trajectory classification methods. Here, we propose a ship trajectory classification method based on multi-attribute trajectory similarity metrics which utilizes the following steps: (1) Improve the Douglas–Peucker (DP) algorithm by considering the SOG and COG; (2) use a multi-attribute symmetric segmentation path distance (MSSPD) for the similarity metric between trajectories; (3) cluster the segmented sub-trajectories based on the density-based spatial clustering of applications with noise (DBSCAN) algorithm; (4) adaptively determinate the optimal input parameters based on the proposed comprehensive clustering performance metrics. The proposed method was tested on real AIS data from Bohai Sea waters, and the experimental results show that the algorithm can accurately cluster the ship trajectory groups and extract traffic distributions in key waters.

This study is primarily intended to present a damage constitutive equation under the combined action of confining pressures and freeze–thaw cycles by subjecting deep expansive clay to the consolidated undrained triaxial tests. We study the influence of the numbers of freeze–thaw cycles on various mechanical indexes of soil by using the TSZ-2 instrument (fully automatic triaxial instrument). As the number of freeze–thaw cycles increases, the ultimate peak stress of the soil decreases, and then, the effect of the freeze–thaw effect on the shear strength gradually weakened. By combining the expression method of the damage variable under the action of loading alone with the expression method under the action of freeze–thaw cycles alone, we brought in the damage evolution equation to obtain the damage constitutive equation under the combined action of confining pressures and freeze–thaw cycles. The stress values under three confining pressures (100 kPa, 200 kPa, and 300 kPa) can be determined by using the final damage constitutive model. The measured data with a water content of 17% and six freeze–thaw cycles were compared with the theoretical data. The actual strength values were 118.4 kPa, 152.3 kPa, and 184.1 kPa, and the theoretical strength values were 120 kPa, 150 kPa, and 186 kPa. The fitting degree of the strength value was as high as 99%, which verifies the feasibility of this model. This study can serve as an available reference for well wall construction and disaster prediction in deep coal mining.

Background: Ovarian cancer is the second leading cause of gynecologic cancer-associated deaths. Cancer stemness and chemoresistance are responsible for ovarian cancer metastasis and the poor prognosis of patients. In this study, we determined the function of N6-methyladenine (m6A) RNA methylation and prostaglandin E receptor 2 (PTGER2) in ovarian cancer progression. Methods: The m6A RNA methylation-associated PTGER2 in ovarian cancer was identified using bioinformatics analysis. The role of PTGER2 in ovarian cancer was elucidated in cell lines and clinical samples with cellular and molecular experiments. Results: In this investigation, bioinformatics analysis based on a public cancer database was used to elucidate the impact of m6A modification on the prognosis of patients with ovarian cancer. Moreover, PTGER2 was identified as a potential oncogene associated with the distant metastasis of ovarian cancer and poor patient prognosis. Interestingly, PTGER2 expression was experimentally shown to be enhanced by N6-adenosine-methyltransferase 70 kDa subunit (METTL3)-mediated m6A modification. In addition, PTGER2 enhanced cancer stem cell self-renewal properties, the epithelial-mesenchymal transition, and DNA damage repair, thus potentiating cell stemness, therapy resistance to carboplatin, proliferation, and metastasis of ovarian cancer. Importantly, PTGER2 expression in clinical samples was associated with distant metastasis, predicted poor patient prognosis, and independently served as a prognostic predictor in ovarian cancer. Conclusions: Our work defines PTGER2 as an oncogene and reveals that PTGER2 is a prognostic predictor and novel therapeutic target for the management of ovarian cancer.

Fritilariae ussuriensis maxim can be used as a medicine with little difficulty in its planting, but owing to its fragile characteristics, Fritilariae ussuriensis maxim is mainly collected by manual excavation. In order to solve the problems of the low working efficiency and poor environmental adaptability of the harvesting equipment of Fritilariae ussuriensis maxim, this paper designs a new excavation device, which can effectively reduce the operation resistance and improve the excavation efficiency of Fritilariae ussuriensis maxim. In this paper, the finite element method and discrete element method are used to simulate and analyze the operation performance of the excavation device. Combined with the orthogonal test and single factor test, the factors affecting the operating performance of the excavating device were explored. The excavating experimental platform was designed and built, and the simulation results were verified with experimental excavation data. This study shows that the operating speed, shovel face inclination angle, and digging depth had significant effects on the digging resistance of the shovel body, with the shovel face inclination angle having the highest influencing factor and the operating speed having the lowest influencing factor. Combined with the orthogonal test analysis and response surface design, the optimal operating parameters of the shovel body are: operating speed 0.5 m/s, shovel face inclination angle 25°, and excavation depth 120 mm.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients’ clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden’s index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders (n = 50) vs. non-responders (n = 36) with a significant difference in OS. In multivariate LR, cardiac dose–volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

The Tiegelongnan Cu (Au, Ag) deposit in central Tibet contains more than 10 Mt of copper ranking 29th in the world. It is characterized by typical porphyry-epithermal alteration and mineralization. In order to improve the understanding of porphyry-epithermal copper deposit in Tibet, new zircon U-Pb age and sulfur isotope data along with published data in the Tiegelongnan are presented to investigate the formation and preservation mechanism. Ore-related intrusive rocks in the Tiegelongnan including Early Cretaceous (about 120 Ma) granodiorite porphyry and diorite porphyry are closely related to the northward subduction of Bangongco-Nujiang ocean. Sulfur mainly comes from deep magma, and ore-forming fluid is affected by both magmatic and meteoric water. The metallogenic setting of Tiegelongnan is consistent with those of Andean porphyry copper deposits in South America. The cover of the Meiriqiecuo Formation volcanic rocks, Lhasa-Qiangtang collision and India-Eurasian collision have significance in the preservation and uplift of the deposit. The formation, preservation and discovery of Tiegelongnan play an important role in exploration of ancient porphyry-epithermal deposits in Tibet.© 2022 China Geology Editorial Office.

Background and aims: Studies on the association between growth-differentiation factor-15 (GDF-15) level and adverse outcomes have yielded conflicting results in patients with stable coronary artery disease (CAD). This meta-analysis aimed to evaluate the association of baseline GDF-15 level with adverse outcomes in stable CAD patients. Methods: Two authors independently searched PubMed and Embase databases from inception to May 31, 2021 for available studies that investigated the association of baseline GDF-15 level with all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events (MACEs) in stable CAD patients. Pooled multivariable adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for the highest vs. the lowest GDF-15 level. Results: Seven studies that involved 28,765 stable CAD patients were identified and analyzed. The meta-analysis showed that the highest GDF-15 level was associated with higher risk of MACEs (HR 1.42; 95% CI 1.29–1.57; p

BackgroundSuperior mesenteric vein (SMV) thrombosis is a rare intestinal ischemic disease. The clinical manifestations of patients differ, and most experience gastrointestinal symptoms.Case summaryA 45-year-old female patient presented with persistent abdominal pain and abnormal vaginal bleeding for 7 days. A physical examination revealed significant abdominal tenderness with positive rebound tenderness. A laboratory examination revealed a white blood cell count of 27 × 109/l, hemoglobin level of 52 g/L, and D-dimer of 4.54 mg/l. Enhanced computed tomography revealed a thickening and swelling of the jejunum and ileum in the left upper quadrant and portal vein. Filling defects in the main lumen and branch lumen suggested the possibility of portal vein and superior mesenteric vein thrombosis. Symptoms improved after treatment with low-molecular-weight heparin and warfarin. One month later, the patient developed occasional dull pain in the left lower quadrant, with long strips of discharge. An electronic colonoscopy revealed avascular necrosis and tissue exfoliation of the intestinal mucosa. After the continuation of warfarin therapy, the abdominal pain resolved. Five months later, the patient experienced recurrent abdominal pain and vomiting. A physical examination revealed a blood pressure of 75/49 mm Hg. An incomplete ileus with the portal and superior mesenteric vein thrombosis was diagnosed, partial jejunectomy and gastrointestinal bypass anastomosis were performed, and warfarin was continued postoperatively.ConclusionThe intestinal mucosal shedding observed, in this case, was caused by SMV thrombosis, which enriched the clinical manifestations of the disease and provided a new basis for the clinical diagnosis of SMV thrombosis.

Abstract In modern power systems, the high penetration of renewable energy challenges system frequency regulation and stability. In such conditions, the demand‐side loads can be aggregated and applied for power system frequency regulation. In this study, a dual‐level distributed control framework is proposed for thermostatically controlled load (TCL) aggregators in multi‐area load frequency control. In the higher control level, the leader of TCL aggregators in each control area is controlled by local and neighbouring area control errors. In the lower control level, multiple TCL aggregators are coupled via a leader‐follower consensus control protocol to track the power reference from the area leader. As a result, the dual‐level distributed controlled TCL aggregators can operate together with synchronous generators for frequency regulation in multi‐area power systems. The proposed method is validated in a three‐area power system under various cyber‐physical conditions, including contingency and normal operation conditions, as well as communication failure and delay conditions.

Numerical simulation of turbulent combustion is a key tool for aeroengine design.Due to the need of high-precision model to Navier-Stokes equation,numerical simulation of turbulent combustion requires huge amount of calculations,and the phy-sicochemical models causes the flow field to be extremely complicated,making the load balancing a bottleneck for large-scale pa-rallelization.We port and optimize the numerical simulation method of turbulent combustion on a powerful computing server,DGX-2.We design the threading method of flux calculation and use Roofline model to guide the optimization.In addition,we design an efficient communication method and propose a multi-GPU parallel method for turbulent combustion based on high-speed interconnection of DGX-2.The results show that the performance of a single V100 GPU is 8.1x higher than that on dual-socket Intel Xeon 6248 CPU node with 40 cores.And the multi-GPU version on DGX-2 with 16 V100 GPUs achieves 66.1x speedup,which is higher than the best performance on CPU cluster.