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Based on the cooperative principle brought up by American philosopher of language named Grice, with exemplification and explanation of the violation of four maxims, this paper also combines the cooperative principle with hedges, analyzing the translation of hedges so as to better manage implicit and explicit information in the translation. Meanwhile, analyzing how conversational maxims operate in a text can contribute to the characterization of style, “the perceived distinctive manner of expression in writing or speaking” (Wales, 2014, p. 397), helping the translator in maintaining a close stylistic link with the original text (Boase-Beier, 2014, p. 394). Analyzing how meaning is constructed or generated via maxims in a fictional text assists the translator in both hearing and recreating the literary style or narrative voice that guides the linguistic choices made by the author (Munday, 2008, p. 19). Take children literature translation as example, this paper not only offers a peek into the causes of explicitation and implicitation in children literature translation, but makes an explanatory study of it. Since the translation of children’s literature should comply with children’s cognition and characteristics so as to reconcile the relation between readability and educational functions, this paper will again analyze how meaning is constructed or generated via maxims in the text. Such analysis will help translators in maintaining the style of the original, which is conducive to managing implicit and explicit information in the translation.

BACKGROUND: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m(5)C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. METHODS: Based on 11 m(5)C regulators, we evaluated the m(5)C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m(5)C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m(5)C modification pattern of individual LUAD patients. RESULTS: Two m(5)C methylation modification patterns were identified according to 11 m(5)C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m(5)C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m(5)C score was constructed to quantify the m(5)C modification pattern of individual LUAD patients. We found that the high m(5)C score group had a better prognosis. The role of the m(5)C score in predicting prognosis was also verified in the dataset GSE31210. CONCLUSIONS: Our study revealed that m(5)C modification played a significant role in TME regulation of LUAD. Investigation of the m(5)C regulation mode may have some implications for tumor immunotherapy in the future.

Nan Jiang,1,2,* Xiao-Lin Ge,2,* Zhao-Yue Zhang,2 Jia Liu,2 Pei-Pei Wang,2 Xin-Chen Sun,1,2 Min Yang1 1The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China; 2Department of Radiotherapy, Jiangsu Province Hospital, Nanjing, Jiangsu, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min YangThe First School of Clinical Medicine, Nanjing Medical University, No. 818 of Tianyuan Road, Jiangning District, Nanjing, Jiangsu, 210000, People’s Republic of ChinaTel +86 13701516659Email yangmin@jsinm.orgXin-Chen SunDepartment of Radiotherapy, Jiangsu Province Hospital, No. 300 of Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, People’s Republic of ChinaTel +86 13770662828Email sunxinchen2012@163.comPurpose: Intensity-modulated radiotherapy (IMRT) can improve the prognosis of patients with esophageal cancer. This study aimed to evaluate clinical factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy (IMRT) alone.Patient and Methods: Data of 103 patients with pathologically confirmed esophageal cancer who were admitted to our hospital between October 2011 and November 2017 were retrospectively reviewed. All patients had squamous cell carcinoma. All patients received IMRT. Patients with stage I–IVA tumors were included to represent the real-world clinical practice. We performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). In univariate analyses, the Kaplan–Meier method was used to estimate OS and PFS for various subgroups. In multivariate analyses, hazard ratios were calculated.Results: Single-factor analysis revealed that T stage (P=0.019), N stage (P =0.047), and lesion length (P =0.000) were associated with the prognosis of esophageal cancer patients who received IMRT. Cox regression analysis revealed that T stage (odds ratio [OR] = 4.68; P < 0.05), N stage (OR = 0.28; P < 0.05), and lesion length (OR = 0.09; P < 0.05) were independent factors relevant to prognosis.Conclusion: T stage, N stage, and lesion length influenced the long-term curative effects of IMRT for esophageal cancer and were prognostic factors for patients with esophageal cancer receiving definitive radiotherapy alone. The higher the stage and the longer the tumor, the lower the survival rate.Keywords: esophageal neoplasms, prognosis, intensity-modulated radiotherapy, retrospective studies

In this paper, the chaotic characteristics of air traffic flow are studied, ADS-B data easily available to ground aviation users are selected as the basic data of traffic flow, and a high-dimensional prediction model of air traffic flow time series based on the non-iterative PSR-ELM algorithm is established. The prediction results of the proposed algorithm are then compared with those of the SVR algorithm, which requires iteration. Moreover, airspace operation data before and after the outbreak of the COVID-19 epidemic are selected as the experimental scene, and the prediction effects of time series with different degrees of chaos are comparatively analyzed. The experimental results reveal that the PSR-ELM algorithm achieves fast and accurate results, and, when the traffic flow state is sparse, the degree of chaos is reduced and the prediction effect is improved. The findings of this research provide a reference for air traffic flow theory.

Objective: To compare the survival benefit between neoadjuvant and adjuvant radiotherapy for non-inflammatory non-metastatic breast cancer patients.Method: We conducted a retrospective cohort study using surveillance, epidemiology and end results databases. Our study recruited patients who had been diagnosed with stage I-III breast cancer and underwent surgery and radiotherapy. The overall survival was calculated by Kaplan Meier method. Cox risk model was used to determine the impact of radiotherapy according to stage, molecular subtype and other risk factors. Propensity score matching was used to balance measurable confounding factors. Results: Of all the 411483 enrolled patients varying from 1975 to 2016, 1712 patients received neoadjuvant radiotherapy, and 409567 patients received adjuvant radiotherapy. Compared with the adjuvant radiotherapy group, the neoadjuvant radiotherapy group showed significantly higher risks of overall mortality and breast cancer-specific mortality. Survival differences in treatment sequences were correlated with stage, molecular subtypes and other risk factors.Conclusion: According to the results of this study, neoadjuvant radiotherapy did not show a survival advantage, and adjuvant radiotherapy is still the primary treatment. However, neoadjuvant radiotherapy also has some theoretical advantages, such as phase reduction and recurrence reduction. Therefore, it is still worthy of further exploration.

Understanding the chaos of air traffic flow is significant to the achievement of advanced air traffic management, and trajectory data are the basic material for studying the chaotic characteristics. However, at present, there are two main obstacles to this task, namely, large amounts of noise in the measured data and the tedium of existing data processing methods. This paper improves the incorrect trajectory processing method based on ADS-B trajectory data and proposes a method by which to quickly extract the traffic flow through a certain waypoint. Currently, the commonly used theoretical analysis tools for nonlinear complex systems include the classical nonlinear dynamics analysis method and the newly developed complex network-based analysis method. The latter is currently in an exploratory stage because it has just been introduced into the study of air traffic flow. From these two perspectives, the chaotic characteristics of air traffic flow are studied in the present work. From the perspective of nonlinear dynamics, the improved C-C method is used to calculate the reliability parameters, namely, the time delay τ and embedding dimension m, of phase-space reconstruction, and the maximum Lyapunov index is calculated by using the small data volume method to prove the existence of chaos in the system. From the perspective of complex networks, the construction of a visibility graph and horizontal visibility graph is used to prove the existence of chaos in the system, and the goodness-of-fit parameters of the degree distributions of two fitting methods under different time scales are evaluated, which provides support for the air traffic flow theory.

Per capita fructose consumption has increased 100-fold over the last century1. Epidemiological studies suggest that excessive fructose consumption, and especially consumption of sweet drinks, is associated with hyperlipidaemia, non-alcoholic fatty liver disease, obesity and diabetes2–7. Fructose metabolism begins with its phosphorylation by the enzyme ketohexokinase (KHK), which exists in two alternatively spliced forms8. The more active isozyme, KHK-C, is expressed most strongly in the liver, but also substantially in the small intestine9,10 where it drives dietary fructose absorption and conversion into other metabolites before fructose reaches the liver11–13. It is unclear whether intestinal fructose metabolism prevents or contributes to fructose-induced lipogenesis and liver pathology. Here we show that intestinal fructose catabolism mitigates fructose-induced hepatic lipogenesis. In mice, intestine-specific KHK-C deletion increases dietary fructose transit to the liver and gut microbiota and sensitizes mice to fructose’s hyperlipidaemic effects and hepatic steatosis. In contrast, intestine-specific KHK-C overexpression promotes intestinal fructose clearance and decreases fructose-induced lipogenesis. Thus, intestinal fructose clearance capacity controls the rate at which fructose can be safely ingested. Consistent with this, we show that the same amount of fructose is more strongly lipogenic when drunk than eaten, or when administered as a single gavage, as opposed to multiple doses spread over 45 min. Collectively, these data demonstrate that fructose induces lipogenesis when its dietary intake rate exceeds the intestinal clearance capacity. In the modern context of ready food availability, the resulting fructose spillover drives metabolic syndrome. Slower fructose intake, tailored to intestinal capacity, can mitigate these consequences. Modulating the capacity of the intestinal epithelium to catabolize fructose is shown to alter fructose-induced lipogenesis in the mouse liver, suggesting that fructose clearance in the small intestine protects from steatosis.

Background: The optimal therapeutic strategy in locally advanced esophageal squamous cell carcinoma (ESCC) primarily treated by surgery remains unknown. This study was designed to evaluate the impact of postoperative chemoradiotherapy and postoperative sequential chemoradiotherapy on survival in this population. Methods: The study included a total of 228 consecutive patients who underwent radical esophagectomy and were confirmed to have stage pT3–4 or pN+ ESCC from September 2011 to September 2017 at our institution. All patients received postoperative radiotherapy with or without concurrent or sequential chemotherapy after esophagectomy. Univariate and multivariate analyses were used to compare the survival of patients with postoperative radiotherapy, postoperative concurrent chemoradiotherapy, and postoperative sequential chemoradiotherapy. Results: After a median follow-up of 52 months, the 3- and 5-year overall survival (OS) rates were 70.2% [95% confidence interval (CI), 63.7–76.7%] and 62.2% (95% CI, 54.6–69.8%), respectively. The disease-free survival (DFS) rates at 3 and 5 years were 65.2% (95% CI, 58.7–71.7%) and 55.2% (95% CI, 47.6–62.8%), respectively. The 3- and 5-year locoregional recurrence-free survival (LRFS) rates were 65.1% (95% CI, 58.4–71.8%) and 55.5% (95% CI, 47.7–63.3%). Of the 228 patients, 38 (16.7%) had distant metastases. Subgroup analysis showed that being male and having a higher T stage were independent poor prognostic factors for OS and DFS in patients with pN+ or stage III + IVA ESCC. The results also showed that in patients with stage III + IVA ESCC, the DFS of the patients in the concurrent chemotherapy (CCT) group was improved compared with that in the no CCT group [hazard ratio (HR), 0.551; 95% CI, 0.323–0.938; P=0.028]. Multivariate analysis showed that sequential chemoradiotherapy was associated with poor LRFS (HR, 2.312; 95% CI, 1.078–4.959; P=0.031), especially in stage T3–4 patients, and it was also related to the poor DFS (HR, 1.781; 95% CI, 1.086–2.921; P=0.022) in patients with stage T3–4 ESCC. Conclusions: In patients with locally advanced ESCC, those who underwent sequential chemoradiotherapy had a worse LRFS. Postoperative concurrent chemoradiotherapy was the most effective adjuvant therapy for resected stage III–IVA ESCC. In addition, being male, having a higher T stage, and being node-positive were independent poor prognostic factors for OS and DFS.

BackgroundConcurrent chemoradiotherapy (CCRT) is the standard treatment for nonsurgical esophageal cancer (EC). However, esophageal cancer patients receiving CCRT alone are still unsatisfactory in terms of local control and overall survival (OS) benefit. Clinicians generally add consolidation chemotherapy (CCT) after CCRT. It remains controversial whether CCT following CCRT is beneficial for esophageal cancer. We, therefore, undertook a meta-analysis to assess the need for CCT in inoperable esophageal cancer.Materials and MethodsWe combed PubMed, Embase, Cochrane Library, Web of Science, and CNKI for relevant published articles up to July 2020 that compared CCRT plus CCT to CCRT alone for patients with nonsurgical EC. Our primary endpoint was OS and progression-free survival (PFS), and the secondary endpoint was treatment toxicity. We analyzed the hazard ratio (HR) to estimate the time-to-event data and the odds ratio (OR) to compare the treatment-related effect. To assess heterogeneity, we performed the I2 test and examined publication bias using funnel plots analysis.ResultsThe 11 retrospective studies involved 2008 patients. Of these 2008 patients, 1018 received CCRT plus CCT, and 990 received CCRT. Compared to CCRT alone, CCT after CCRT did not improve disease control rate (DCR) (OR 1.66; 95% CI 0.53–5.15, p=0.384) and objective response rate (ORR) (OR 1.44; 95% CI 0.62–3.35, p=0.393). However, OS (HR 0.72; 95% CI 0.59–0.86, p < 0.001) and PFS (HR 0.61; 95% CI 0.44–0.84, p=0.003) did increase. Our results show that CCT plus CCRT had a clear survival advantage over CCRT alone. The risk of treatment toxicity did not increase for EC patients who received CCT.ConclusionCCT after CCRT significantly increases OS and PFS in patients with nonsurgical EC and could provide them remarkable survival benefits. The results provide an evidence-based framework for the use of CCT after CCRT.

Background To determine the diagnostic accuracy of preoperative T/N stage with magnetic resonance imaging (MRI) in lower and middle rectal cancer patients and the impacts on clinical decision‐making. Patients and methods A total of 211 patients were recruited from October 2015 to March 2017 in this retrospective study. High‐resolution MRI was performed within 2 weeks before surgery. Histopathologic results were evaluated for the postoperative T/N stage and the diagnostic accuracy of MRI was assessed according to the postoperative histopathologic results. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were evaluated for T/N staging and κ values were used to evaluate MRI consistent analysis compared with postoperative histopathologic staging. Results The overall MRI diagnostic accuracy was 79.62% for T1‐4 staging and 54.50% for N0‐2 staging. The κ values were 0.619 and 0.255 for T1‐4 and N0‐2 staging, respectively. The diagnostic accuracy of MRI for treatment decision‐making was 80.57%. Conclusion MRI allows a highly accurate preoperative assessment of T stage but only a fairly accurate preoperative assessment of N stage for rectal cancer. The diagnostic accuracy of MRI for treatment decision‐making is promising, but additional studies are needed to validate these findings in a larger sample size from multiple centers.

To scientifically evaluate the reliability of air traffic networks, a definition of air traffic network reliability is proposed in this paper. Calculation models of the connectivity reliability, travel-time reliability, and capacity reliability of the air traffic network are constructed based on collected historical data, considering the current status and the predicted future evolution trends. Considering the randomness and fuzziness of factors affecting reliability, a comprehensive evaluation model of air traffic networks based on the uncertainty transformation model is established. Finally, the reliability of the US air traffic network is analyzed based on data published by the Transportation Statistics Bureau of the US Department of Transportation. The results show that the connectivity reliability is 0.4073, the capacity reliability is 0.8300, the travel-time reliability is 0.9180, and the overall reliability evaluated is &ldquo, relatively reliable&rdquo, This indicates that although the US structural reliability is relatively low, the US air traffic management is very efficient, and the overall reliability is strong. The reliability in nonpeak hours is much higher than that in peak hours. The method can identify air traffic network reliability efficiently. The main factors affecting reliability can be found in the calculation process, and are beneficial for air traffic planning and management. The empirical analysis also reflects that the evaluation model based on the uncertainty transformation model can transform the quantitative data of network structure and traffic function into the qualitative language of reliability.

Background: The management of rectal carcinoma has substantially evolved over the past two decades, so as AJCC staging and NCCN guidelines. The inherent relationships of pathologic factors warrant further study. The present study aimed to assess the associations of clinical and pathological factors in rectal cancer patients undergoing radical surgery.Methods: From October 2015 to February 2019, all rectal cancer patients treated with radical surgery without neoadjuvant therapy were identified. The analysis was performed with data obtained from the prospectively collected database. Predictive factors for lymph node metastasis were analysed.Results: In total, 692 patients with a median age of 61.64 years (range: 22-89) were included. There was no significant difference in onset age between male and female patients (61.75±11.10 vs 61.43±11.92, P=0.723).Tumour location (P=0.004), perineural invasion (PNI) (P=0.000), lymphovascular invasion (LVI) (P=0.000), tumour deposit (TD) (P=0.000), and differentiation grade (P=0.000) were significantly related to pathologic T stage in univariate analysis, while sex was not (p=0.192).Compared to patients with T1 disease, there was a significantly higher proportion of positive LVI in patients with stage T3 disease (P=0.011, OR=3.404, 95% CI: 1.319-8.787) but not in those with T2 (P=0.686, OR=0.804, 95% CI: 0.280-2.310) and T4 (P=0.063, OR=3.200, 95% CI: 0.941-10.886) disease. Compared to patients with T2 disease, there was a significantly higher proportion of perineural invasion in patients with stage T3 (P=0.000, OR=6.2376, 95% CI: 3.371-11.685) but not T4 (P=0.172, OR=2.309, 95% CI: 0.694-7.676) disease. Compared to patients with T1 disease, a significantly higher proportion of TDs occurred in patients with stage T3 (P=0.013, OR=6.106, 95% CI: 1.455-25.631) and stage T4 (P=0.019, OR=7.146, 95% CI: 1.378-37.044) but not stage T2 (P=0.435, OR=0.503, 95% CI: 0.089-2.824) disease. The overall incidence of lymph node metastasis was 44.9% (19.6% for T1, 23.6% for T2, 56.7% for T3, and 67.8% for T4). Patient age, sex, and tumour location did not significantly affect lymph node metastasis (LNM). The presence of LVI (OR=3.882, 95% CI=2.338-6.440, P=0.000), TD (OR=27.645, 95% CI=9.805-77.947, P=0.000), higher T stage (OR=1.969, 95% CI=1.471-2.635, P=0.000), and poorly differentiated histology (OR=2.255, 95% CI=1.544-3.293, P=0.000) were associated with a higher incidence of LNM on multivariate analysis. Perineural invasion (P=0.000) significantly affected LNM in univariate but not multivariate analysis (OR=1.213, 95% CI=0.734-2.003, P=0.452).Conclusion: There was no significant difference between male and female patients in onset age. Tumour location, PNI, LVI, TD, and differentiation grade were significantly related to pathologic T stage. Patients with the presence of LVI and TD, higher T stage, and poorly differentiated histology have a significantly higher chance of LNM.

SUMMARYMammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting both for circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.

NADH provides electrons for aerobic ATP production. In cells deprived of oxygen or with impaired electron transport chain activity, NADH accumulation can be toxic. To minimize such toxicity, elevated NADH inhibits the classical NADH producing pathways: glucose, glutamine, and fat oxidation. Here, through deuterium tracing studies in cultured cells and mice, we show that folate-dependent serine catabolism also produces substantial NADH. Strikingly, when respiration is impaired, serine catabolism through methylene tetrahydrofolate dehydrogenase (MTHFD2) becomes a major NADH source. In cells whose respiration is slowed by hypoxia, metformin, or genetic lesions, mitochondrial serine catabolism inhibition partially normalizes NADH levels and facilitates cell growth. In mice with engineered mitochondrial complex I deficiency (NDUSF4-/-), serine’s contribution to NADH is elevated and progression of spasticity is modestly slowed by pharmacological blockade of serine degradation. Thus, when respiration is impaired, serine catabolism contributes to toxic NADH accumulation.

Automated modulation classification plays a very important part in cognitive radio networks. Deep learning is also a powerful tool that we could not overlook its potential in addressing signal modulation recognition problem. In our last work, we propose a new data conversion algorithm in order to gain a better classification accuracy of communication signal modulation, but we still believe that the convolution neural network (CNN) can work better. However, its application to signal modulation recognition is often hampered by insufficient data and overfitting. Here, we propose a smart approach to programmatic data augmentation method by using the auxiliary classifier generative adversarial networks (ACGANs). The famous CNN model, AlexNet, has been utilized to be the classifier and ACGAN to be the generator, which will enlarge our data set. In order to alleviate the common issues in the traditional generative adversarial nets training, such as discriminator overfitting, generator disconverge, and mode collapse, we apply several training tricks in our training. With the result on original data set as our baseline, we will evaluate our result on enlarged data set to validate the ACGAN’s performance. The result shows that we can gain 0.1~6% increase in the classification accuracy in the ACGAN-based data set.

NADPH donates high-energy electrons for antioxidant defence and reductive biosynthesis. Cytosolic NADP is recycled to NADPH by the oxidative pentose-phosphate pathway (oxPPP), malic enzyme 1 (ME1) and isocitrate dehydrogenase 1 (IDH1). Here we show that any one of these routes can support cell growth, but the oxPPP is uniquely required to maintain a normal NADPH/NADP ratio, mammalian dihydrofolate reductase (DHFR) activity and folate metabolism. These findings are based on CRISPR deletions of glucose-6-phosphate dehydrogenase (G6PD, the committed oxPPP enzyme), ME1, IDH1 and combinations thereof in HCT116 colon cancer cells. Loss of G6PD results in high NADP, which induces compensatory increases in ME1 and IDH1 flux. But the high NADP inhibits DHFR, resulting in impaired folate-mediated biosynthesis, which is reversed by recombinant expression of Escherichia coli DHFR. Across different cancer cell lines, G6PD deletion produced consistent changes in folate-related metabolites, suggesting a general requirement for the oxPPP to support folate metabolism. The oxidative pentose-phosphate pathway (oxPPP) is a major NADPH producer. Here the authors show that malic enzyme or isocitrate dehydrogenase can support the growth of cells lacking the oxPPP, but the oxPPP is necessary to maintain a normal NADPH/NADP ratio, DHFR activity and folate metabolism.

Background To determine the diagnostic accuracy of preoperative T/N stage using MRI in lower and middle rectal cancer patients and the impacts on clinical decision-making. Patients and methods There were 354 patients recruited from May 2017 to February 2019. MRI was performed within 2 weeks before surgery. Histopathologic results were evaluated for the postoperative T/N stage and MRI diagnostic accuracy was assessed based on the postoperative histopathologic results. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and Kappa values were used to evaluate MRI diagnostic accuracy and analysis consistency compared with postoperative histopathologic staging. Results Overall MRI diagnostic accuracy was 78.2% and 56.8% for T1–4 and N0–2 staging. The Kappa values were 0.625 and 0.323 for T1–4 and N0–2 staging, respectively. After combination, MRI diagnostic accuracy was 85% and 69.5% for T and N staging. The Kappa values were 0.693 and 0.4 for T and N staging. The diagnostic accuracy of MRI for treatment decision-making was 79.1%. Conclusion MRI enables a highly accurate preoperative assessment of T stage but only a fairly accurate preoperative assessment of the N stage for rectal cancer with surgery. The diagnostic accuracy of MRI for treatment decision-making is promising.

In this paper, information entropy and ensemble learning based signal recognition theory and algorithms have been proposed. We have extracted 16 kinds of entropy features out of 9 types of modulated signals. The types of information entropy used are numerous, including Renyi entropy and energy entropy based on S Transform and Generalized S Transform. We have used three feature selection algorithms, including sequence forward selection (SFS), sequence forward floating selection (SFFS) and RELIEF-F to select the optimal feature subset from 16 entropy features. We use five classifiers, including k-nearest neighbor (KNN), support vector machine (SVM), Adaboost, Gradient Boosting Decision Tree (GBDT) and eXtreme Gradient Boosting (XGBoost) to classify the original feature set and the feature subsets selected by different feature selection algorithms. The simulation results show that the feature subsets selected by SFS and SFFS algorithms are the best, with a 48% increase in recognition rate over the original feature set when using KNN classifier and a 34% increase when using SVM classifier. For the other three classifiers, the original feature set can achieve the best recognition performance. The XGBoost classifier has the best recognition performance, the overall recognition rate is 97.74% and the recognition rate can reach 82% when the signal to noise ratio (SNR) is −10 dB.

Expression map of the 11 prognostic lncRNAs across four UCEC subtypes. Kruskal-Wallis test was used to compare expression levels for each lncRNAs across four UCEC subtypes. (DOC 765 kb)

lncRNAs significantly associated with overall survival in univariate Cox regression analyses. (DOC 38 kb)

Much understanding of metabolism is based on monitoring chemical reactions in cells with isotope tracers. For this purpose, 13C is well suited due to its stable incorporation into bio-molecules and minimal kinetic isotope effect. For redox reactions, however, deuterium tracing can provide valuable additional information. To date, studies examining NADPH production with deuterated carbon sources have failed to account for roughly half of NADPH’s redox active hydrogen. Here we show that the missing hydrogen is the result of enzyme-catalyzed H-D exchange between water and NADPH. While isolated NADPH does not undergo H-D exchange with water, such exchange is catalyzed by Flavin enzymes and occurs rapidly in cells. Correction for H-D exchange is required for accurate assessment of the biological sources of NADPH’s high energy electrons. Deuterated water (D2O) is frequently used to monitor fat synthesis in vivo, but the chemical pathway of the deuteron into fat remains unclear. We show that D2O labels fatty acids primarily via NADPH. Knowledge of this labeling route enables calculation, without any fitting parameters, of the mass isotope distributions of fatty acids from cells grown in D2O. Thus, knowledge of enzyme-catalyzed H-D exchange between water and NADPH enables chemically accurate interpretation of deuterium tracing studies of redox cofactor and fatty acid metabolism.

Deregulation of long non-coding RNAs (lncRNAs) expression has been proven to be involved in the development and progression of cancer. However, expression pattern and prognostic value of lncRNAs in breast cancer recurrence remain unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients who did or did not develop recurrence by repurposing existing microarray datasets from the Gene Expression Omnibus database, and identified 12 differentially expressed lncRNAs that were closely associated with tumor recurrence of breast cancer patients. We constructed a lncRNA-focus molecular signature by the risk scoring method based on the expression levels of 12 relapse-related lncRNAs from the discovery cohort, which classified patients into high-risk and low-risk groups with significantly different recurrence-free survival (HR = 2.72, 95% confidence interval 2.07–3.57; p = 4.8e-13). The 12-lncRNA signature also represented similar prognostic value in two out of three independent validation cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was independent of known clinical prognostic factors in at least two cohorts. Functional analysis suggested that the predicted relapse-related lncRNAs may be involved in known breast cancer-related biological processes and pathways. Our results highlighted the potential of lncRNAs as novel candidate biomarkers to identify breast cancer patients at high risk of tumor recurrence.

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology and have been implicated in the development and progression of cancers. However, the prognostic significance of lncRNAs in diffuse large-B-cell lymphoma (DLBCL) remains unclear and needs to be systematically investigated. In this study, we obtained and analyzed lncRNA expression profiles in three cohorts of 1043 DLBCL patients by repurposing the publicly available microarray datasets from the Gene Expression Omnibus (GEO) database. In the discovery series of 207 patients, we identified a set of six lncRNAs that was significantly associated with patients’ overall survival (OS) using univariate Cox regression analysis. The six prognostic lncRNAs were combined to form an expression-based six-lncRNA signature which classified patients of the discovery series into the high-risk group and low-risk group with significantly different survival outcome (HR = 2.31, 95% CI = 1.8 to 2.965, p

Aim This meta-analysis was designed to fully assess the curative effects of radiotherapy-based therapies for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Methods English articles were retrieved through searching Cochrane library, PubMed, and Embase databases updated to February 2017. Studies were selected based on the inclusion and exclusion criteria. The curative effects of radiotherapy-based therapies forHER2+ BC patients were assessed using hazard rates (HRs) or odds ratios (ORs), as well as their 95% confidence intervals (CIs). In addition, Egger test was used to assess publication bias, followed by sensitivity analysis. All statistic methods were conducted using R 3.12 software. Results A total of 9 eligible studies were included into this meta-analysis, which involved 2236 HER2+ BC patients. Egger test showed that the eligible studies had no publication bias (t = 2.198, P = .05918). Sensitivity analysis demonstrated that the results were stable. HER2+ BC patients in radiotherapy group had lower locoregional recurrences than those in other groups. Moreover, meta-analysis showed that no significant difference was found between HER2+ BC patients in radiotherapy group and other groups on the 1-year overall survival (P = 0.5263, I = 65.4%), 3-year overall survival (P = 0.4591, I = 0), and 5-year overall survival (P = 0.06277, I = 0). Conclusion Radiotherapy-based therapies might have certain advantages in treating HER2+ BC patients.

Glucose is catabolized by two fundamental pathways, glycolysis to make ATP and the oxidative pentose phosphate pathway to make reduced nicotinamide adenine dinucleotide phosphate (NADPH). The first step of the oxidative pentose phosphate pathway is catalyzed by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here we develop metabolite reporter and deuterium tracer assays to monitor cellular G6PD activity. Using these, we show that the most widely cited G6PD antagonist, dehydroepiandosterone, does not robustly inhibit G6PD in cells. We then identify a small molecule (G6PDi-1) that more effectively inhibits G6PD. Across a range of cultured cells, G6PDi-1 depletes NADPH most strongly in lymphocytes. In T cells but not macrophages, G6PDi-1 markedly decreases inflammatory cytokine production. In neutrophils, it suppresses respiratory burst. Thus, we provide a cell-active small molecule tool for oxidative pentose phosphate pathway inhibition, and use it to identify G6PD as a pharmacological target for modulating immune response.