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Intelligent methods such as deep learning provide an innovative optimization path for English teaching in colleges and universities. In this paper, the attention mechanism is based on traditional CNN. Embedded attention and multilayer convolutional feature fusion are used to complete the design of streamlined bilinear attention networks. The streamlined bilinear attention network is used to obtain the characteristics of students’ classroom behavior in the process of English teaching, combine the characteristics of students’ classroom behavior and computer programming language to design and implement the intelligent interactive teaching system of English in colleges and universities, and test and apply the analysis of the intelligent interactive teaching system of English. The results show that in the query performance test report, even though the number of requests issued in the test is 2,000, the error rate is always kept at 0, the throughput is 39.8, and the response time is kept at 95~1144s, which indicates that this system can meet the performance requirements with a moderate number of users. In the application analysis, the total score of the teaching method of English Intelligent Interactive Teaching System (mean=94.62) is higher than that of the traditional English teaching method (mean=89.65), which indicates that the teaching method of English Intelligent Interactive Teaching System is more capable of improving the interaction and communication ability of the students in English teaching. The system constructed in this study can meet the diverse needs of students and contribute to the quality improvement of English teaching in colleges and universities.

The optimized sparrow search algorithm (ISSA) is built on top of the deep neural network (DNN) in this paper, along with a new deep recurrent neural network (DRNN) algorithm that is proposed by improving the DNN. Ultimately, an ISSA-DRNN-based model for assessing the quality of English course teaching has been established. To examine the application impact of the ISSA-DRNN-based English course quality teaching evaluation model, SA University has been chosen as the study location. Two groups have been created: an experimental group and a control group. The experimental group’s academic level scores grew by 5.1 points in terms of English achievement, whereas the control group’s average score increased by 0.36 points, indicating a very significant difference (P

Prioritizing genes for translation to therapeutics for common diseases has been challenging. Here, we propose an approach to identify drug targets with high probability of success by focusing on genes with both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). We find 98 BEST genes for a variety of indications. Drugs targeting those genes are 3.8-fold more likely to be approved than non-BEST genes. We focus on five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants in those genes result in significantly increased risk for idiopathic short stature (ISS) (OR = 2.75, p = 3.99 × 10-8). Finally, using functional experiments, we demonstrate that adding an exogenous CNP analog (encoded by NPPC) rescues the phenotype, thus validating its potential as a therapeutic treatment for ISS. Our results show the value of looking for bidirectional effects to identify and validate drug targets.

Fibrosis is the process whereby cells at a damaged site are transformed into fibrotic tissue, comprising fibroblasts and an extracellular matrix rich in collagen and fibronectin, following damage to organs or tissues that exceeds their repair capacity. Depending on the affected organs or tissues, fibrosis can be classified into types such as pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and cardiac fibrosis. The primary pathological features of fibrotic diseases include recurrent damage to normal cells and the abnormal activation of fibroblasts, leading to excessive deposition of extracellular matrix and collagen in the intercellular spaces. However, the etiology of certain specific fibrotic diseases remains unclear. Recent research increasingly suggests that the cytoskeleton plays a significant role in fibrotic diseases, with structural changes in the cytoskeleton potentially influencing the progression of organ fibrosis. This review examines cytoskeletal remodeling and its impact on the transformation or activation of normal tissue cells during fibrosis, potentially offering important insights into the etiology and therapeutic strategies for fibrotic diseases. [ABSTRACT FROM AUTHOR]

In recent decades, the advent of coronaviruses has engendered multiple large-scale infectious outbreaks, leading to profound human casualties and posing a significant menace to global public health. At the crux of the coronavirus lifecycle, the assembly and release phases emerge as pivotal processes, necessitating meticulous investigation into the underlying mechanisms. This paper systematically expounds upon the intricate assembly and packaging mechanisms intrinsic to coronaviruses, scrutinizes the diverse release pathways employed by these viruses, and delves into the discourse surrounding targeted antiviral drugs. The comprehensive insights encapsulated in this exposition serve as valuable reference points for formulating effective strategies in the prevention and treatment of coronavirus infections. [ABSTRACT FROM AUTHOR]

CDK9 is the kinase subunit of positive transcription elongation factor b (P-TEFb) that enables RNA polymerase (Pol) II's transition from promoter-proximal pausing to productive elongation. Although considerable interest exists in CDK9 as a therapeutic target, little progress has been made due to lack of highly selective inhibitors. Here, we describe the development of i-CDK9 as such an inhibitor that potently suppresses CDK9 phosphorylation of substrates and causes genome-wide Pol II pausing. While most genes experience reduced expression, MYC and other primary response genes increase expression upon sustained i-CDK9 treatment. Essential for this increase, the bromodomain protein BRD4 captures P-TEFb from 7SK snRNP to deliver to target genes and also enhances CDK9's activity and resistance to inhibition. Because the i-CDK9-induced MYC expression and binding to P-TEFb compensate for P-TEFb's loss of activity, only simultaneously inhibiting CDK9 and MYC/BRD4 can efficiently induce growth arrest and apoptosis of cancer cells, suggesting the potential of a combinatorial treatment strategy.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell–cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-[beta]1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis., Author(s): Guoying Yu [1]; Argyris Tzouvelekis [1, 2]; Rong Wang [1]; Jose D Herazo-Maya [1]; Gabriel H Ibarra [1]; Anup Srivastava [1]; Joao Pedro Werneck de Castro [3, 4]; Giuseppe [...]