Impeding DNA Polymerase ß Activity by Oleic Acid to Inhibit Base Excision Repair and Induce Mitochondrial Dysfunction in Hepatic Cells.

Free fatty acids (FFAs) hepatic accumulation and the resulting oxidative stress contribute to several chronic liver diseases including nonalcoholic steatohepatitis. However, the underlying pathological mechanisms remain unclear. In this study, we propose a novel mechanism whereby the toxicity of FFAs detrimentally affects DNA repair activity. Specifically, we have discovered that oleic acid (OA), a prominent dietary free fatty acid, inhibits the activity of DNA polymerase ß (Pol ß), a crucial enzyme involved in base excision repair (BER), by actively competing with 2'-deoxycytidine-5'-triphosphate. Consequently, OA hinders the efficiency of BER, leading to the accumulation of DNA damage in hepatocytes overloaded with FFAs. Additionally, the excessive presence of both OA and palmitic acid (PA) lead to mitochondrial dysfunction in hepatocytes. These findings suggest that the accumulation of FFAs hampers Pol ß activity and contributes to mitochondrial dysfunction, shedding light on potential pathogenic mechanisms underlying FFAs-related diseases.

Corrigendum: Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel.

[This corrects the article DOI: 10.3389/fonc.2022.993243.].

Multi-scenario pear tree inflorescence detection based on improved YOLOv7 object detection algorithm.

Efficient and precise thinning during the orchard blossom period is a crucial factor in enhancing both fruit yield and quality. The accurate recognition of inflorescence is the cornerstone of intelligent blossom equipment. To advance the process of intelligent blossom thinning, this paper addresses the issue of suboptimal performance of current inflorescence recognition algorithms in detecting dense inflorescence at a long distance. It introduces an inflorescence recognition algorithm, YOLOv7-E, based on the YOLOv7 neural network model. YOLOv7 incorporates an efficient multi-scale attention mechanism (EMA) to enable cross-channel feature interaction through parallel processing strategies, thereby maximizing the retention of pixel-level features and positional information on the feature maps. Additionally, the SPPCSPC module is optimized to preserve target area features as much as possible under different receptive fields, and the Soft-NMS algorithm is employed to reduce the likelihood of missing detections in overlapping regions. The model is trained on a diverse dataset collected from real-world field settings. Upon validation, the improved YOLOv7-E object detection algorithm achieves an average precision and recall of 91.4% and 89.8%, respectively, in inflorescence detection under various time periods, distances, and weather conditions. The detection time for a single image is 80.9 ms, and the model size is 37.6 Mb. In comparison to the original YOLOv7 algorithm, it boasts a 4.9% increase in detection accuracy and a 5.3% improvement in recall rate, with a mere 1.8% increase in model parameters. The YOLOv7-E object detection algorithm presented in this study enables precise inflorescence detection and localization across an entire tree at varying distances, offering robust technical support for differentiated and precise blossom thinning operations by thinning machinery in the future.

Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel.

The expression of O-GlcNAc transferase (OGT) and its catalytic product, O-GlcNAcylation (O-GlcNAc), are elevated in many types of cancers, including prostate cancer (PC). Inhibition of OGT serves as a potential strategy for PC treatment alone or combinational therapy. PC is the second common cancer type in male worldwide, for which chemotherapy is still the first-line treatment. However, the function of inhibition of OGT on chemotherapeutic response in PC cells is still unknown. In this study, we show that inhibition of OGT by genetic knockdown using shRNA or by chemical inhibition using OGT inhibitors sensitize PC cells to docetaxel, which is the most common chemotherapeutic agent in PC chemotherapy. Furthermore, we identified that microRNA-140 (miR-140) directly binds to OGT mRNA 3' untranslated region and inhibits OGT expression. Moreover, docetaxel treatment stimulates miR-140 expression, whereas represses OGT expression in PC cells. Overexpression of miR-140 enhanced the drug sensitivity of PC cells to docetaxel, which could be reversed by overexpression of OGT. Overall, this study demonstrates miR-140/OGT axis as therapeutic target in PC treatment and provides a promising adjuvant therapeutic strategy for PC therapy.