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Oxygen and nutrient deprivation are common features of solid tumors. Although abnormal alternative splicing (AS) has been found to be an important driving force in tumor pathogenesis and progression, the regulatory mechanisms of AS that underly the adaptation of cancer cells to harsh microenvironments remain unclear. Here, we found that hypoxia- and nutrient deprivation-induced asparagine endopeptidase (AEP) specifically cleaved DDX3X in a HIF1A-dependent manner. This cleavage yields truncated carboxyl-terminal DDX3X (tDDX3X-C), which translocates and aggregates in the nucleus. Unlike intact DDX3X, nuclear tDDX3X-C complexes with an array of splicing factors and induces AS events of many premRNAs; for example, enhanced exon skipping (ES) in exon 2 of the classic tumor suppressor PRDM2 leads to a frameshift mutation of PRDM2. Intriguingly, the isoform ARRB1-[DELTA]exon 13 binds to glycolytic enzymes and regulates glycolysis. By utilizing in vitro assays, glioblastoma organoids, and animal models, we revealed that AEP/tDDX3X-C promoted tumor malignancy via these isoforms. More importantly, high AEP/tDDX3X-C/ARRB1- [DELTA]exon 13 in cancerous tissues was tightly associated with poor patient prognosis. Overall, our discovery of the effect of AEP-cleaved DDX3X switching on alternative RNA splicing events identifies a mechanism in which cancer cells adapt to oxygen and nutrient shortages and provides potential diagnostic and/or therapeutic targets., Introduction In the tumor microenvironment, cells often face a certain degree of oxygen and nutrient deprivation. Cancer cells strive to survive and proliferate in this harsh environment in multiple ways, [...]

Intermittent bus lanes (IBLs) can improve road capacity by allowing other regular vehicles to drive in the idle space of a dedicated bus lane. However, excessive vehicles in the IBL will cause additional bus delays. To avoid such problems, this study proposes a method to determine the capability of IBL permitted for regular vehicles first, and then use it as the total amount restriction of lane-borrowing vehicles to implement a bus lane control strategy that will improve road capacity and avoid additional bus delays. A model for calculating the capability of IBL is also provided. Vehicles between two buses are designated as potentially lane-borrowing vehicles that could follow the buses to leave the road section. The evolution process of these vehicles in the unit is analyzed using kinematic wave theory to obtain the formed traffic queue length. Using the rear bus trajectory to set the length limit on the traffic queue, the estimated total amount of lane-borrowing vehicles is corrected to establish the final capability of the IBL. The applicability of the method was evaluated from three perspectives: bus departure interval, road traffic saturation, and near-side bus stop. The simulation results showed that the proposed method can guarantee no additional bus delay compared to the situation of a dedicated bus lane. It can also improve road capacity more than traditional IBL under any degree of saturation and bus departure interval. Compared with traditional IBL, the average travel time of regular vehicles is shorter, except when the degree of saturation is high and the bus departure interval is large., Author(s): Yingying Lin [1,2]; Nan Zhang [1,2]; Hongzhao Dong (corresponding author) [1,2] 1. Introduction A dedicated bus lane (DBL) [1] ensures stable operation of public transport. However, in practice, due [...]

Background: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E‐FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. Methods: An Attention U‐net and a U‐net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. Results: In 10 random tests, the Attention U‐net and U‐net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U‐net performed better at identifying negative images than the U‐net, which had an average specificity of 91% compared to 86% for the U‐net. Additionally, the Attention U‐net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U‐net's average dice coefficient of 0.82. Conclusions: The Attention U‐net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E‐FAST in clinical work. [ABSTRACT FROM AUTHOR]

The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.