Role of hypoxia in cellular senescence

This work was supported by the National Natural Science Foundation of China (Grant no. 31972741) ; MH CZ-DRO (UHHK, 00179906) ; Grant Agency of the Czech Republic (20-22037S) ; Research Program of University of Granada; and Scientific Grant Agency (VEGA Project 1/0482/20).Senescent cells persist and continuously secrete proinflammatory and tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, and Alzheimer's disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates that hypoxia is involved in the regulation of cellular senescence. Hypoxia-inducible factor (HIF)-1 alpha accumulates under hypoxic conditions and regulates cellular senescence by modulating the levels of the senescence markers p16, p53, lamin B1, and cyclin D1. Hypoxia is a critical condition for maintaining tumor immune evasion, which is promoted by driving the expression of genetic factors (such as p53 and CD47) while triggering immunosenescence. Under hypoxic conditions, autophagy is activated by targeting BCL-2/adenovirus E1B 19kDa interacting protein 3, which subsequently induces p21(WAF1/CIP1) as well as p16(Ink4a) and increases beta-galactosidase (beta-gal) activity, thereby inducing cellular senescence. Deletion of the p21 gene increases the activity of the hypoxia response regulator poly (ADP-ribose) polymerase-1 (PARP-1) and the level of nonhomologous end joining (NHEJ) proteins, repairs DNA double-strand breaks, and alleviates cellular senescence. Moreover, cellular senescence is associated with intestinal dysbiosis and an accumulation of D-galactose derived from the gut microbiota. Chronic hypoxia leads to a striking reduction in the amount of Lactobacillus and D-galactose-degrading enzymes in the gut, producing excess reactive oxygen species (ROS) and inducing senescence in bone marrow mesenchymal stem cells. Exosomal microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play important roles in cellular senescence. miR-424-5p levels are decreased under hypoxia, whereas lncRNA-MALAT1 levels are increased, both of which induce cellular senescence. The present review focuses on recent advances in understanding the role of hypoxia in cellular senescence. The effects of HIFs, immune evasion, PARP-1, gut microbiota, and exosomal mRNA in hypoxia-mediated cell senescence are specifically discussed. This review increases our understanding of the mechanism of hypoxia-mediated cellular senescence and provides new clues for anti-aging processes and the treatment of aging-related diseases.National Natural Science Foundation of China (NSFC) 31972741MH CZ-DRO (UHHK) 00179906Grant Agency of the Czech Republic Norwegian Agency for Development Cooperation - NORAD 20-22037SResearch Program of University of GranadaVedecka grantova agentura MSVVaS SR a SAV (VEGA) 1/0482/2

Frame-wise Cross-modal Matching for Video Moment Retrieval

Video moment retrieval targets at retrieving a moment in a video for a given language query. The challenges of this task include 1) the requirement of localizing the relevant moment in an untrimmed video, and 2) bridging the semantic gap between textual query and video contents. To tackle those problems, early approaches adopt the sliding window or uniform sampling to collect video clips first and then match each clip with the query. Obviously, these strategies are time-consuming and often lead to unsatisfied accuracy in localization due to the unpredictable length of the golden moment. To avoid the limitations, researchers recently attempt to directly predict the relevant moment boundaries without the requirement to generate video clips first. One mainstream approach is to generate a multimodal feature vector for the target query and video frames (e.g., concatenation) and then use a regression approach upon the multimodal feature vector for boundary detection. Although some progress has been achieved by this approach, we argue that those methods have not well captured the cross-modal interactions between the query and video frames. In this paper, we propose an Attentive Cross-modal Relevance Matching (ACRM) model which predicts the temporal boundaries based on an interaction modeling. In addition, an attention module is introduced to assign higher weights to query words with richer semantic cues, which are considered to be more important for finding relevant video contents. Another contribution is that we propose an additional predictor to utilize the internal frames in the model training to improve the localization accuracy. Extensive experiments on two datasets TACoS and Charades-STA demonstrate the superiority of our method over several state-of-the-art methods. Ablation studies have been also conducted to examine the effectiveness of different modules in our ACRM model.Comment: 12 pages; accepted by IEEE TM

Topographic effects on wave resonance in the narrow gap between fixed box and vertical wall

Multiple coastal and offshore structures deployed side by side with narrow gap may be subject to large-amplitude free surface resonance, which can lead to green water on the deck and cause rapid increase of hydrodynamic loading on structures. Here, the resonant motions of the free surface inside a narrow gap between a fixed box and a vertical wall excited by incident regular waves with various wave heights are simulated using a two-dimensional numerical wave tank. The topographies of plane slopes with different inclinations are deployed in front of the vertical wall. The main focus of this paper is on the influences of the topographical variation on the fluid resonance inside the narrow gap. For the first time, it is found that the fluid resonant frequency decreases monotonously with the topographical slope, and both the amplification of the resonant wave height and the reflection coefficient present a pattern of fluctuation with the slope. For all the topographies considered in this paper, both the fluid resonant frequency and the amplification of the resonant wave height are shown to decrease with the incident wave height; while the variation trend of the reflection coefficient with the incident wave height depends on the topographical slope

Comparison of retinal thickness measurements of normal eyes between topcon algorithm and a graph based algorithm

To assess the agreement between Topcon built-in algorithm and our developed graph based algorithm, the retinal thickness of 9-sectors on an Early Treatment of Diabetic Retinopathy Study(ETDRS) chart measurements for normal subjects was compared. A total of fifty eyes were enrolled in this study. The overall and sectoral thickness on ETDRS chart were calculated using Topcon built-in algorithm and our developed three-dimensional graph based algorithm. Correlation analysis and agreement analysis were performed between the commercial algorithm and our algorithm. A high degree of correlation was found between the results obtained from the two methods was from 0.856 to 0.960. It’s showed that our developed graph based algorithm can provide excellent performance similar to Topcon algorithm