ABSTRACT
Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.
Subject(s)
Cisplatin , Drug Resistance, Neoplasm , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors , Neural Cell Adhesion Molecule L1 , Humans , Cisplatin/pharmacology , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/metabolism , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/genetics , Neural Cell Adhesion Molecule L1/metabolism , Neural Cell Adhesion Molecule L1/genetics , Cell Line, Tumor , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasm Metastasis , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination/drug effects , Mice , Cell Proliferation/drug effects , Tripartite Motif Proteins , DNA-Binding Proteins , Nuclear ProteinsABSTRACT
Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.
Subject(s)
Glutamic Acid , Spleen , Mice , Male , Animals , Semen , Glutamine , Aspartic Acid , Metabolomics/methods , Liver/metabolism , Alanine/metabolism , Amino Sugars/metabolism , Water/metabolism , Nucleotides/metabolism , Purines/metabolism , Sugars , Chromatography, High Pressure Liquid , Biomarkers/metabolismABSTRACT
Emotion recognition utilizing EEG signals has emerged as a pivotal component of human-computer interaction. In recent years, with the relentless advancement of deep learning techniques, using deep learning for analyzing EEG signals has assumed a prominent role in emotion recognition. Applying deep learning in the context of EEG-based emotion recognition carries profound practical implications. Although many model approaches and some review articles have scrutinized this domain, they have yet to undergo a comprehensive and precise classification and summarization process. The existing classifications are somewhat coarse, with insufficient attention given to the potential applications within this domain. Therefore, this article systematically classifies recent developments in EEG-based emotion recognition, providing researchers with a lucid understanding of this field's various trajectories and methodologies. Additionally, it elucidates why distinct directions necessitate distinct modeling approaches. In conclusion, this article synthesizes and dissects the practical significance of EEG signals in emotion recognition, emphasizing its promising avenues for future application.
ABSTRACT
Transforming growth factor (TGF)-ß is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-ß can stimulate diverse cellular responses and is particularly critical to embryonic development, wound healing, tissue homeostasis, and immune homeostasis in health. The dysfunction of TGF-ß can play key roles in many diseases, and numerous targeted therapies have been developed to rectify its pathogenic activity. In the past decades, a large number of studies on TGF-ß signaling have been carried out, covering a broad spectrum of topics in health, disease, and therapeutics. Thus, a comprehensive overview of TGF-ß signaling is required for a general picture of the studies in this field. In this review, we retrace the research history of TGF-ß and introduce the molecular mechanisms regarding its biosynthesis, activation, and signal transduction. We also provide deep insights into the functions of TGF-ß signaling in physiological conditions as well as in pathological processes. TGF-ß-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted. Through the summary of previous knowledge and recent updates, this review aims to provide a systematic understanding of TGF-ß signaling and to attract more attention and interest to this research area.
Subject(s)
Signal Transduction , Transforming Growth Factor beta , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , CytokinesABSTRACT
Calpain, a key member of the Calpain cysteine protease superfamily, performs limited protein hydrolysis in a calcium-dependent manner. Its activity is tightly regulated due to the potential for non-specific cleavage of various intracellular proteins upon aberrant activation. A thorough review of the literature from 2010 to 2023 reveals 121 references discussing cardiovascular and cerebrovascular diseases. Dysregulation of the Calpain system is associated with various pathological phenomena, including lipid metabolism disorders, inflammation, apoptosis, and excitotoxicity. Although recent studies have revealed the significant role of Calpain in cardiovascular and cerebrovascular diseases, the precise mechanisms remain incompletely understood. Exploring the potential of Calpain inhibition as a therapeutic approach for the treatment of cardiovascular and cerebrovascular diseases may emerge as a compelling area of interest for future calpain research.
ABSTRACT
Functional magnetic resonance imaging (fMRI) has become one of the most common imaging modalities for brain function analysis. Recently, graph neural networks (GNN) have been adopted for fMRI analysis with superior performance. Unfortunately, traditional functional brain networks are mainly constructed based on similarities among region of interests (ROIs), which are noisy and can lead to inferior results for GNN models. To better adapt GNNs for fMRI analysis, we propose DABNet, a Deep DAG learning framework based on Brain Networks for fMRI analysis. DABNet adopts a brain network generator module, which harnesses the DAG learning approach to transform the raw time-series into effective brain connectivities. Experiments on two fMRI datasets demonstrate the efficacy of DABNet. The generated brain networks also highlight the prediction-related brain regions and thus provide interpretations for predictions.
ABSTRACT
@# Objective: To investigate the expression of Tim-3 on the surface of T cells in patients with esophageal cancer, and to explore its clinical significance. Methods: Fresh tumor tissues, paracancerous tissues, and peripheral blood were collected from 25 patients with esophageal cancer at the first affiliated Hospital of Zhengzhou University from September 2016 to April 2018. Peripheral blood from 10 healthy subjects was also collected during the same time period. The expressions of Tim-3, early apoptotic molecules and intrinsic factors in tumor tissues and peripheral blood PBMCs of 25 esophageal cancer patients were determined by flow cytometry. Also, the correlation between Tim-3+ T cell proportion and pathological parameters was investigated. The expression of Tim-3 in tumor tissues and paracancerous tissues was detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). TCGA database was used to further verify the expression of Tim-3 in tumor tissues and paracancerous tissues, as well as its relationship with prognosis. Results: Tim-3 expression on T cells was higher in tumor tissues from esophageal cancer patients (P<0.01). Tim-3+ T cell function was in an exhausted status(P<0.05 or P<0.01), and the expression of Tim-3 on the surface of T cells in esophageal cancer microenvironment was closely related to lymph node metastasis and clinical staging (all P<0.01). Conclusion: Taken together, Tim3 expression on the surface of T cells could induce T cell dysfunction in patients with esophageal cancer, suggesting that Tim-3 may serve as a potential therapeutic target for esophageal cancer.
ABSTRACT
Objective@#To explore the prevalence of sexting among secondary vocational school students and to examine the correlation between sexting and mental health, so as to provide evidence for prevention and intervention on adolescents mental health.@*Methods@#In April 2021, three secondary vocational schools from central urban area, outskirts and outer suburbs in Shanghai, among 1 580 students were selected by cluster sampling.@*Results@#The proportions of students who received and who forwarded others private photos or videos were 11.96% and 2.78%, respectively. The proportion of students who sent others personal photos or videos was 2.54%. And the proportions of boys were higher than those of girls ( χ 2=45.89, 24.09, 6.66, P <0.01). The results of multivariable Logistic analysis showed that compared with those who had never sexted, students who had ever had any sexting were at higher risk of anxiety ( OR=2.40, 95%CI =1.59-3.61), depression( OR=1.86, 95%CI =1.25-2.75), non suicidal self injury intention ( OR=2.34, 95%CI =1.48-3.69) and suicidal intention ( OR=2.96, 95%CI =1.83-4.79)( P < 0.05 ).@*Conclusion@#There is a significant correlation between sexting and mental health among secondary vocational school students. The latent risks of sexting should be included in the curriculum of comprehensive sex education for teenagers to enhance their media literacy and decision making capability, so as to prevent sexual assault or abuse caused by sexting and promote sexual and reproductive health and as well as mental health of adolescents.
ABSTRACT
Objective@#To explore the association between mothers reactions to adolescents exposure to intimate shots and pornography use of junior high school students, and to provide references for family communications on sexual topics in similar scenarios.@*Methods@#A total of 1 760 students from grade 6 to 8 in three junior high schools in a certain district of Shanghai were selected by cluster sampling. Self-filled questionnaires on tablets were used to collect data.@*Results@#The proportion of junior high school students who watched pornography was 26.36%(464), and that of boys (29.83%,270/905) was higher than of girls (22.69%,194/855). Most junior high school students believed that mothers reactions to adolescents exposure to intimate shots would be “taking the opportunity to educate teenagers not to do this” (30.54%) or “avoiding adolescents watching intimate shots” (42.24%). The results of multivariable analysis showed that comparing with junior high school students who believed that mothers would “watch together without making any comments ”, students who believed that mothers would “take the opportunity to educate teenagers not to do this”(OR=0.43, 95%CI=0.29-0.64) and “avoid adolescents watching intimate shots”(OR=0.56, 95%CI=0.39-0.80) were at lower risk of viewing pornography (P<0.01).@*Conclusion@#There is a significant correlation between junior high school students pornography use and mothers possible reactions to adolescents exposure to intimate shots. Family sex education and parental monitoring should be emphasized, and parents awareness of communicating sexual issues with adolescents should be strengthened.