Inhibition of the rapamycin-insensitive mTORC1 /4E-BP1 axis attenuates TGF-ß1-induced fibrotic response in human Tenon's fibroblasts.

Subconjunctival fibrosis is the major cause of failure in both conventional and modern minimally invasive glaucoma surgeries (MIGSs) with subconjunctival filtration. The search for safe and effective anti-fibrotic agents is critical for improving long-term surgical outcomes. In this study, we investigated the effect of inhibiting the rapamycin-insensitive mTORC1/4E-BP1 axis on the transforming growth factor-beta 1(TGF-ß1)-induced fibrotic responses in human Tenon's fibroblasts (HTFs), as well as in a rat model of glaucoma filtration surgery (GFS). Primary cultured HTFs were treated with 3 ng/mL TGF-ß1 for 24 h, followed by treatment with 10 µM CZ415 for additional 24 h. Rapamycin (10 µM) was utilized as a control for mTORC1/4E-BP1 signaling insensitivity. The expression levels of fibrosis-associated molecules were measured using quantitative real-time PCR, Western blotting, and immunofluorescence analysis. Cell migration was assessed through the scratch wound assay. Additionally, a rat model of GFS was employed to evaluate the anti-fibrotic effect of CZ415 in vivo. Our findings indicated that both rapamycin and CZ415 treatment significantly reduced the TGF-ß1-induced cell proliferation, migration, and the expression of pro-fibrotic factors in HTFs. CZ415 also more effectively inhibited TGF-ß1-mediated collagen synthesis in HTFs compared to rapamycin. Activation of mTORC1/4E-BP signaling following TGF-ß1 exposure was highly suppressed by CZ415 but was only modestly inhibited by rapamycin. Furthermore, CZ415 was found to decrease subconjunctival collagen deposition in rats post GFS. Our results suggest that rapamycin-insensitive mTORC1/4E-BP1 signaling plays a critical role in TGF-ß1-driven collagen synthesis in HTFs. This study demonstrated that inhibition of the mTORC1/4E-BP1 axis offers superior anti-fibrotic efficacy compared to rapamycin and represents a promising target for improving the success rate of both traditional and modern GFSs.

Forecasting oil consumption with attention-based IndRNN optimized by adaptive differential evolution.

Accurate prediction of oil consumption plays a dominant role in oil supply chain management. However, because of the effects of the coronavirus disease 2019 (COVID-19) pandemic, oil consumption has exhibited an uncertain and volatile trend, which leads to a huge challenge to accurate predictions. The rapid development of the Internet provides countless online information (e.g., online news) that can benefit predict oil consumption. This study adopts a novel news-based oil consumption prediction methodology-convolutional neural network (CNN) to fetch online news information automatically, thereby illustrating the contribution of text features for oil consumption prediction. This study also proposes a new approach called attention-based JADE-IndRNN that combines adaptive differential evolution (adaptive differential evolution with optional external archive, JADE) with an attention-based independent recurrent neural network (IndRNN) to forecast monthly oil consumption. Experimental results further indicate that the proposed news-based oil consumption prediction methodology improves on the traditional techniques without online oil news significantly, as the news might contain some explanations of the relevant confinement or reopen policies during the COVID-19 period.

Identification of RPGR ORF15 mutation for X-linked retinitis pigmentosa in a large Chinese family and in vitro correction with prime editor.

X-linked retinitis pigmentosa (XLRP) is the most severe form of Retinitis Pigmentosa (RP) and one of the leading causes of blindness in the world. Currently, there is no effective treatment for RP. In the present study, we recruited a XLRP family and identified a 4 bp deletion mutation (c. 2234_2237del) in RPGR ORF15 with Sanger sequencing, which was located in the exact same region as the missing XES (X chromosome exome sequencing) coverage. Then, we generated cell lines harboring the identified mutation and corrected it via enhanced prime editing system (ePE). Collectively, Sanger sequencing identified a pathogenic mutation in RPGR ORF15 for XLRP which was corrected with ePE. This study provides a valuable insight for genetic counseling of the afflicted family members and prenatal diagnosis, also paves a way for applying prime editing based gene therapy in those patients.

Interpretable tourism demand forecasting with temporal fusion transformers amid COVID-19.

An innovative ADE-TFT interpretable tourism demand forecasting model was proposed to address the issue of the insufficient interpretability of existing tourism demand forecasting. This model effectively optimizes the parameters of the Temporal Fusion Transformer (TFT) using an adaptive differential evolution algorithm (ADE). TFT is a brand-new attention-based deep learning model that excels in prediction research by fusing high-performance prediction with time-dynamic interpretable analysis. The TFT model can produce explicable predictions of tourism demand, including attention analysis of time steps and the ranking of input factors' relevance. While doing so, this study adds something unique to the literature on tourism by using historical tourism volume, monthly new confirmed cases of travel destinations, and big data from travel forums and search engines to increase the precision of forecasting tourist volume during the COVID-19 pandemic. The mood of travelers and the many subjects they spoke about throughout off-season and peak travel periods were examined using a convolutional neural network model. In addition, a novel technique for choosing keywords from Google Trends was suggested. In other words, the Latent Dirichlet Allocation topic model was used to categorize the major travel-related subjects of forum postings, after which the most relevant search terms for each topic were determined. According to the findings, it is possible to estimate tourism demand during the COVID-19 pandemic by combining quantitative and emotion-based characteristics.

Interpretable tourism volume forecasting with multivariate time series under the impact of COVID-19.

This study proposes a novel interpretable framework to forecast the daily tourism volume of Jiuzhaigou Valley, Huangshan Mountain, and Siguniang Mountain in China under the impact of COVID-19 by using multivariate time-series data, particularly historical tourism volume data, COVID-19 data, the Baidu index, and weather data. For the first time, epidemic-related search engine data is introduced for tourism demand forecasting. A new method named the composition leading search index-variational mode decomposition is proposed to process search engine data. Meanwhile, to overcome the problem of insufficient interpretability of existing tourism demand forecasting, a new model of DE-TFT interpretable tourism demand forecasting is proposed in this study, in which the hyperparameters of temporal fusion transformers (TFT) are optimized intelligently and efficiently based on the differential evolution algorithm. TFT is an attention-based deep learning model that combines high-performance forecasting with interpretable analysis of temporal dynamics, displaying excellent performance in forecasting research. The TFT model produces an interpretable tourism demand forecast output, including the importance ranking of different input variables and attention analysis at different time steps. Besides, the validity of the proposed forecasting framework is verified based on three cases. Interpretable experimental results show that the epidemic-related search engine data can well reflect the concerns of tourists about tourism during the COVID-19 epidemic.

Forecasting the U.S. oil markets based on social media information during the COVID-19 pandemic.

Accurate oil market forecasting plays an important role in the theory and application of oil supply chain management for profit maximization and risk minimization. However, the coronavirus disease 2019 (COVID-19) has compelled governments worldwide to impose restrictions, consequently forcing the closure of most social and economic activities. The latter leads to the volatility of the oil markets and poses a huge challenge to oil market forecasting. Fortunately, the social media information can finely reflect oil market factors and exogenous factors, such as conflicts and political instability. Accordingly, this study collected vast online oil news and used convolutional neural network to extract relevant information automatically. Oil markets are divided into four categories: oil price, oil production, oil consumption, and oil inventory. A total of 16,794; 9,139; 8,314; and 8,548 news headlines were collected in four respective cases. Experimental results indicate that social media information contributes to the forecasting of oil price, oil production and oil consumption. The mean absolute percentage errors are respectively 0.0717, 0.0144 and 0.0168 for the oil price, production, and consumption prediction during the COVID-19 pandemic. Marketers must consider the impact of social media information on the oil or similar markets, especially during the COVID-19 outbreak.