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In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities.

Objectives: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. Methods: A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid‐axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10–50 mL, 50–100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland–Altman graph. Results: Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland–Altman plot shows the proportion of samples outside the limit was below 5%. Conclusions: CNN‐based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency. [ABSTRACT FROM AUTHOR]

To explore the effects of N fertilizer rates on seed yield and quality of winter rapeseed, field experiments were carried out in Wuxue County, Hubei Province during 2019/2020 and 2020/2021 seasons. The experiments were set at five nitrogen application levels of 0, 90, 180, 270, and 360 kg N hm-2. Rapeseed yield, N concentration, and rapeseed quality indexes were measured at maturity stage. The results showed that N application significantly increased rapeseed yield and N content. Compared with the zero N application, the average yield increase after N application was 1548 kg N hm-2, and the average yield increase rate was up to 32.9%. Within the range of N application rate of 0--270 kg N hm-2, rapeseed yield increased significantly with the application of N fertilizer. If N application was continued, rapeseed yield did not change significantly or had a downward trend. N application mainly improved rapeseed yield by increasing the number of pods per plant. N application significantly increased protein content in rapeseed. When the N application rate was 270 kg N hm-2, the protein content was the highest. N application significantly reduced the seed oil content. For every 100 kg N hm-2 increase in nitrogen application, the seed oil content decreased by 1.6%. With the increase of N fertilizer application rate, glucosinolate, oleic acid, linolenic acid, erucic acid, and saturated fatty acids (palmitic acid and stearic acid) increased, while linoleic acid decreased in rapeseed. Rapeseed quality decreased as a whole. In conclusion, to pursue high-quality edible oil and take into account rapeseed yield, the application rate of N fertilizer was 180 kg N hm-2. The optimal application rate of N fertilizer was 270 kg N hm-2 when rapeseed yield and rapeseed cake were taken into account. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi‐targeted metabolomic analysis on 56 COVID‐19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID‐19 patients. A meta‐analysis was performed on published metabolic data of COVID‐19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs= 0.442, p = 0.005). Mini meta‐analysis indicated elevated glutamate was related to increased risk of COVID‐19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID‐19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID‐19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID‐19 severity in multiple populations, which might confer potential therapeutic target of COVID‐19, especially for severe patients. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering effects in rodent models of diabetes. In this study, we found that FGF-21 can significantly attenuate ischemia-reperfusion (I/R) induced damage in H9c2 cells (rat heart). However, it is unclear which signal transduction pathway is involved in the cardioprotective effect of FGF-21. Thus, this study was designed to investigate the potential mechanism induced by FGF-21. The results showed that FGF-21 treatment prevented the oxidative stress and apoptosis associated with I/R damage by reducing the levels of superoxide anions, inhibiting glycogen synthase kinase (GSK) 3β by activating Akt phosphorylation, and recovering the levels of ATP synthase pyruvate kinase isozymes M1 and protein kinase C, thereby improving energy supply. In summary, we conclude that FGF-21 protects H9c2 cells against I/R injury mainly through the Akt-GSK-3β-caspase-3 dependent pathway, preventing oxidative stress, and recovery of the energy supply. Key words: FGF-21, myocardial ischemia-reperfusion, H9c2, proteomics, Akt, ROS, apoptosis, signaling pathway. Le facteur de croissance des fibroblastes (FGF)-21 est nouveau regulateur du transport de glucose independant de l'insuline dans les adipocytes 3T3-L1 qui diminue le glucose et les triglycerides dans des modeles de diabete chez le rongeur. Dans cette etude, nous avons trouve que le FGF-21 pouvait attenuer significativement le dommage induit par l'ischemiereperfusion (I/R) chez les cellules H9c2. Cependant, la voie de transduction impliquee dans l'effet cardioprotecteur du FGF-21 n'est pas clairement definie. Ainsi, cette etude a ete concue pour examiner le mecanisme d'action potentiel du FGF-21. Les resultats ont montre que le traitement au FGF-21 prevenait le stress oxydant et l'apoptose associes au dommage d'I/R en reduisant les anions superoxydes, inhibait la glycogene synthase kinase (GSK)-3β en activant la phosphorylation d'Akt, et restaurait l'ATP synthase, les isozymes M1 de la pyruvate kinase et la proteine kinase C afin d'ameliorer l'apport en energie. En resume, nous concluons que le FGF-21 protege les cellules H9c2 du dommage d'I/R principalement par l'intermediaire de la voie dependante d'Akt-GSK-3β-caspase-3, du stress anti-oxydant et de la restauration de l'apport energetique. [Traduit par la Redaction] Mots-cles: FGF-21, ischemie-reperfusion myocardique, H92c, proteomique, Akt, ERO, apoptose, voie de signalisation., Introduction It has been reported that ischemia-reperfusion (I/R) injury is commonly associated with oxidative stress, and that reactive oxygen species (ROS) are the major mediators contributing to acute myocardial injury [...]