DDX39B (also called UAP56 or BAT1) which is a kind of DEAD-box family helicase plays pivotal roles in mRNA binding, splicing, and export. It has been found upregulated in many kinds of tumors as an oncogene. Nevertheless, the underlying molecular mechanisms of DDX39B in the proliferation of human colorectal cancer (CRC) remain fairly elusive. In our study, function experiments including the CCK8 and colony formation assay revealed that DDX39B facilitates CRC proliferation in vitro. DDX39B knockdown cells were administered for the orthotopic CRC tumor xenograft mouse model, after which tumor growth was monitored and immunohistochemistry (IHC) was performed to prove that DDX39B can also facilitates CRC proliferation in vivo. Flow cytometry demonstrated that DDX39B promotes the proliferation of CRC cells by driving the cell cycle from G0/G1 phase to the S phase. Mechanistically, RNA-binding protein immunoprecipitation-sequencing (RIP-seq) confirmed that DDX39B binds directly to the first exon of the CDK6/CCND1 pre-mRNA and upregulates their expression. Splicing experiments in vitro using a RT-PCR and gel electrophoresis assay confirmed that DDX39B promotes CDK6/CCND1 pre-mRNA splicing. Rescue experiments indicated that CDK6/CCND1 is a downstream effector of DDX39B-mediated CRC cell proliferation. Collectively, our results demonstrated that DDX39B and CDK6/CCND1 direct interactions serve as a CRC proliferation promoter, which can accelerate the G1/S phase transition to enhance CRC proliferation, and can offer novel and emerging treatment strategies targeting this cell proliferation-promoting gene.

Objective: To study the role of the receptor for advanced glycation end products (RAGE) in endothelial barrier dysfunction induced by heat stress, to further explore the signal pathway by which RAGE contributes to heat-induced endothelia response, and thereby find a novel target for the clinical treatment of ALI (acute lung injury) induced by heatstroke. Methods: This study established the animal model of heatstroke using RAGE knockout mice. We observed the role of RAGE in acute lung injury induced by heatstroke in mice by evaluating the leukocytes, neutrophils, and protein concentration in BALF (Bronchoalveolar lavage fluids), lung wet/dry ratio, histopathological changes, and the morphological ultrastructure of lung tissue and arterial blood gas analysis. To further study the mechanism, we established a heat stress model of HUVEC and concentrated on the role of RAGE and its signal pathway in the endothelial barrier dysfunction induced by heat stress, measuring Transendothelial electrical resistance (TEER) and western blot. Results: RAGE played a key role in acute lung injury induced by heatstroke in mice. The mechanism C-Jun is located in the promoter region of the RAGE gene. C-Jun increased the RAGE protein expression while HSF1 suppressed RAGE protein expression. The overexpressed RAGE protein then increased HUVEC monolayer permeability by activating ERK and P38 MAPK under heat stress. Conclusion: This study indicates the critical role of RAGE in heat stress-induced endothelial hyperpermeability in acute lung injury and suggests that RAGE could be a potential therapeutic target in protecting patients against acute lung injury induced by heatstroke.

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Background Wireless capsule endoscopy (WCE) is considered to be a powerful instrument for the diagnosis of intestine diseases. Convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist the detection of WCE images. We aimed to perform a systematic review of the current research progress to the CNN application in WCE. Methods A search in PubMed, SinoMed, and Web of Science was conducted to collect all original publications about CNN implementation in WCE. Assessment of the risk of bias was performed by Quality Assessment of Diagnostic Accuracy Studies-2 risk list. Pooled sensitivity and specificity were calculated by an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity. Results 16 articles with 23 independent studies were included. CNN application to WCE was divided into detection on erosion/ulcer, gastrointestinal bleeding (GI bleeding), and polyps/cancer. The pooled sensitivity of CNN for erosion/ulcer is 0.96 [95% CI 0.91, 0.98], for GI bleeding is 0.97 (95% CI 0.93–0.99), and for polyps/cancer is 0.97 (95% CI 0.82–0.99). The corresponding specificity of CNN for erosion/ulcer is 0.97 (95% CI 0.93–0.99), for GI bleeding is 1.00 (95% CI 0.99–1.00), and for polyps/cancer is 0.98 (95% CI 0.92–0.99). Conclusion Based on our meta-analysis, CNN-dependent diagnosis of erosion/ulcer, GI bleeding, and polyps/cancer approached a high-level performance because of its high sensitivity and specificity. Therefore, future perspective, CNN has the potential to become an important assistant for the diagnosis of WCE.