Boundary-Aware Proposal Generation Method for Temporal Action Localization

The goal of Temporal Action Localization (TAL) is to find the categories and temporal boundaries of actions in an untrimmed video. Most TAL methods rely heavily on action recognition models that are sensitive to action labels rather than temporal boundaries. More importantly, few works consider the background frames that are similar to action frames in pixels but dissimilar in semantics, which also leads to inaccurate temporal boundaries. To address the challenge above, we propose a Boundary-Aware Proposal Generation (BAPG) method with contrastive learning. Specifically, we define the above background frames as hard negative samples. Contrastive learning with hard negative mining is introduced to improve the discrimination of BAPG. BAPG is independent of the existing TAL network architecture, so it can be applied plug-and-play to mainstream TAL models. Extensive experimental results on THUMOS14 and ActivityNet-1.3 demonstrate that BAPG can significantly improve the performance of TAL

Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells

The present study aims to understand the mechanism of the lens epithelial cell’s strong anti-apoptotic capacity and survival in the mature human lens that, on the one hand, maintains lens transparency over several decades, while on the other hand, increases the risk of posterior capsule opacification (PCO). Here we compared FHL124 cells and HeLa cells, spontaneously immortalized epithelial cell lines derived from the human lens and cervical cancer cells, respectively, of their resistance to TNFα-mediated cell death. TNFα plus cycloheximide (CHX) triggered almost all of HeLa cell death. FHL124 cells, however, were unaffected and able to block caspase-8 activation as well as prevent caspase-3 and PARP-1 cleavage. Interestingly, despite spontaneous NFκB and AP-1 activation and upregulation of multiple cell survival/anti-apoptotic genes in both cell types, only FHL124 cells were able to survive the TNFα challenge. After screening and comparing the cell survival genes, cFLIP was found to be highly expressed in FHL124 cells and substantially upregulated by TNFα stimulation. FHL124 cells with a mild cFLIP knockdown manifested a profound apoptotic response to TNFα stimulus similar to HeLa cells. Most importantly, we confirmed these findings in an ex vivo lens capsular bag culture system. In conclusion, our results show that cFLIP is a critical gene that is regulating lens epithelial cell survival

Revisiting Hard Negative Mining in Contrastive Learning for Visual Understanding

Efficiently mining and distinguishing hard negatives is the key to Contrastive Learning (CL) in various visual understanding tasks. By properly emphasizing the penalty of hard negatives, Hard Negative Mining (HNM) can improve the CL performance. However, there is no method to quantitatively analyze the penalty strength of hard negatives, which makes training difficult to converge. In this paper, we propose a method for measuring and controlling the penalty strength. We first define a penalty strength metric to provides a quantitative analysis tool for HNM. Then, we propose a Triplet loss with Penalty Strength Control (T-PSC), which can balance the penalty strength of hard negatives and the difficulty of model optimization. In order to verify the effectiveness of the proposed T-PSC method in different modalities, we applied it to two visual understanding tasks: Image–Text Retrieval (ITR) for multi-model processing, and Temporal Action Localization (TAL) for video processing. T-PSC can be applied to existing ITR and TAL models in a plug-and-play manner without any changes. Experiments combined with existing models show that a reasonable control of the penalty strength can speed up training and improve the performance on higher-level tasks

Hyperoxia induces glucose metabolism reprogramming and intracellular acidification by suppressing MYC/MCT1 axis in lung cancer

The perils and promises of inspiratory hyperoxia (IH) in oncology are still controversial, especially for patients with lung cancer. Increasing evidence shows that hyperoxia exposure is relevant to the tumor microenvironment. However, the detailed role of IH on the acid-base homeostasis of lung cancer cells remains unclear. In this study, the effects of 60% oxygen exposure on intra- and extracellular pH were systematically evaluated in H1299 and A549 cells. Our data indicate that hyperoxia exposure reduces intracellular pH, which might be expected to reduce the proliferation, invasion, and epithelial-to-mesenchymal transition of lung cancer cells. RNA sequencing, Western blot, and PCR analysis reveal that monocarboxylate transporter 1 (MCT1) mediates intracellular lactate accumulation and intracellular acidification of H1299 and A549 cells at 60% oxygen exposure. In vivo studies further demonstrate that MCT1 knockdown dramatically reduces lung cancer growth, invasion, and metastasis. The results of luciferase and ChIP-qPCR assays further confirm that MYC is a transcription factor of MCT1, and PCR and Western blot assays confirm that MYC is downregulated under hyperoxic conditions. Collectively, our data reveal that hyperoxia can suppress the MYC/MCT1 axis and cause the accumulation of lactate and intracellular acidification, thereby retarding tumor growth and metastasis

Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification

Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)) are two critical elements in PCO initiation and progression pathogenesis. While PCO marginally impacts aged cataract surgery patients, PCO incidences are exceptionally high in infants and children undergoing cataract surgery. The gene expression of lens epithelial cell aging and its role in the discrepancy of PCO prevalence between young and older people have not been fully studied. Here, we conducted a comprehensive differentially expressed gene (DEG) analysis of a cell aging model by comparing the early and late passage FHL124 lens epithelial cells (LECs). In vitro, TGFβ2, cell treatment, and in vivo mouse cataract surgical models were used to validate our findings. We found that aged LECs decelerated rates of cell proliferation accompanied by dysregulation of cellular immune response and cell stress response. Surprisingly, we found that LECs systematically downregulated epithelial–mesenchymal transition (EMT)-promoting genes. The protein expression of several EMT hallmark genes, e.g., fibronectin, αSMA, and cadherin 11, were gradually decreased during LECs aging. We then confirmed these findings in vitro and found that aged LECs markedly alleviated TGFβ2-mediated EMT. Importantly, we explicitly confirmed the in vitro findings from the in vivo mouse cataract surgery studies. We propose that both the high proliferation rate and EMT-enriched young LECs phenotypic characteristics contribute to unusually high PCO incidence in infants and children

PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR

Maintaining the integrity and protecting the stability of tight junctions in endothelial cells is a potential therapeutic strategy against myocardial ischaemia. Laminin receptors (67LR) are highly expressed on endothelial cell membranes and are associated with endothelial barrier function. Herein, we sought to demonstrate the direct effects of pigment epithelial-derived factor (PEDF) on tight junctions between endothelial cells via 67LR during acute myocardial infarction (AMI) and elucidate its underlying mechanisms. We detected that PEDF directly increased the level of the tight junction protein zonula occludens protein 1 (ZO-1) after overexpression in vitro and in vivo using Western blotting. Evans Blue/TTC staining showed that PEDF significantly reduced the size of the infarcted myocardium. Immunofluorescence and the transwell cellular experiments suggested that PEDF significantly upregulated PI3K-AKT permeability and the distribution of ZO-1 between endothelial cells under OGD conditions. Interestingly, PEDF significantly upregulated the phosphorylation levels of PI3K-AKT-mTOR under oxygen and glucose deprivation conditions but had no significant effects on the total protein expression. The protective effect of PEDF on ZO-1 was significantly inhibited following the inhibition of PI3K-AKT-mTOR. The activation of phosphorylation of PI3K-AKT-mTOR by PEDF was blocked after silencing 67LR, as were the protective effects of PEDF on ZO-1. Therefore, we have reason to believe that PEDF increased ZO-1 expression through the 67LR-dependent PI3K-AKT-mTOR signaling pathway, thus maintaining tight junction stability and protecting cardiac function

Effects of Salinity on Growth Performance, Digestive Enzymes, and Nonspecific Immunity in Juvenile Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂)

In recent years, many studies on the effects of salinity on fish growth performance have been performed. A series of research results confirmed that appropriate salinity could guarantee healthy fish growth, while under extremely high or low salinity, the fish growth would be inhibited. Therefore, salinity is one of the critical factors ensuring aquaculture success. However, most previous studies only focused on fish growth and survival, without systematically analyzing the physiological and biochemical indicators or performing regression analysis of optimal salinity, especially for the hybrid grouper (Epinephelus fuscoguttatus♀×E. lanceolatus♂). A 28-day experiment was conducted to evaluate the effects of different salinities on growth performance, body composition, digestive enzyme activities, antioxidant indices, and serum biochemical indices of the juvenile hybrid grouper [initial mean weight of (29.99±2.60) g]. This study used six salinity levels of 10, 15, 20, 25, 30, and 35, named S1 (control), S2, S3, S4, S5, and S6, respectively. During the experiment, the water temperature was kept at 25–28 ℃, DO≥6 mg/L, pH 8–9, and the contents of ammonia and nitrite nitrogen were both lower than 0.1 mg/L. Firstly, the results showed that different salinity levels had different impacts on the juvenile hybrid grouper growth performance. The weight growth rate (WGR) and special growth rate (SGR) first increased and then decreased with the rise in salinity and peaked in the S4 group, which were significantly higher than those of the S1 and S6 groups (P 0.05). The quadratic regression model analysis based on WGR and FE indicated that the optimal salinities were 22.18 and 23.16. Secondly, the whole fish crude lipid content in the S4 group (10.86%) was significantly higher than in the S1 (9.30%), S2 (9.62%), S3 (9.79%), and S6 (9.22%) groups (P 0.05). The muscle crude protein content and the whole fish and muscle moisture and ash had no significant differences among all groups (P > 0.05). Thirdly, juvenile hybrid grouper´s intestinal lipase and trypsin activities in the S3 and S4 groups were significantly higher than in other groups (P 0.05). Fourthly, salinity changes greatly impacted the antioxidant capacity of the juvenile hybrid grouper liver. The activities of the liver superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) were significantly higher in the S1 and S6 groups than in other groups (P < 0.05). The liver malondialdehyde (MDA) content in the S3 and S4 groups were significantly lower than that of other groups (P < 0.05). Fifthly, lower activity levels of the aspartate aminotransferase (AST), cereal third transaminase (ALT), and alkaline phosphatase (AKP) in serum were found in the S3 and S4 groups, which were significantly lower than those of the S1 and S6 groups (P < 0.05). Moreover, the ALT activity in the S6 group was significantly lower than in the S1 group (P < 0.05). The lower activity level of lactate dehydrogenase (LDH) in serum was also found in the S3 and S4 groups, which were significantly lower than in other groups (P < 0.05). In summary, these results indicated that optimal salinity (20–25 mmol/L) could improve the juvenile hybrid grouper growth, while increasing the activities of digestive enzymes, antioxidant properties, and nonspecific immunity capacity, protecting the fish health. At the same time, the quadratic regression model analysis based on WGR and FE indicated that the optimal salinity for juvenile hybrid grouper is between 22.18 and 23.16