Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation.

Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

Two decades of a protooncogene TBL1XR1: from a transcription modulator to cancer therapeutic target.

Transducin beta-like 1X-related protein 1 (TBL1XR1) was discovered two decades ago and was implicated as part of the nuclear transcription corepressor complex. Over the past 20 years, the emerging oncogenic function of TBL1XR1 in cancer development has been discovered. Recent studies have highlighted that the genetic aberrations of TBL1XR1 in cancers, especially in hematologic tumors, are closely associated with tumorigenesis. In solid tumors, TBL1XR1 is proposed to be a promising prognostic biomarker due to the correlation between abnormal expression and clinicopathological parameters. Post-transcriptional and post-translational modification are responsible for the expression and function of TBL1XR1 in cancer. TBL1XR1 exerts its functional role in various processes that involves cell cycle and apoptosis, cell proliferation, resistance to chemotherapy and radiotherapy, cell migration and invasion, stemness and angiogenesis. Multitude of cancer-related signaling cascades like Wnt-ß-catenin, PI3K/AKT, ERK, VEGF, NF-κB, STAT3 and gonadal hormone signaling pathways are tightly modulated by TBL1XR1. This review provided a comprehensive overview of TBL1XR1 in tumorigenesis, shedding new light on TBL1XR1 as a promising diagnostic biomarker and druggable target in cancer.

FSTL1: A double-edged sword in cancer development.

Flolistatin-related protein 1 (FSTL1), a secreted glycoprotein that is involved in many physiological functions, has attracted much interest and has been implicated in a wide range of diseases, including heart diseases and inflammatory diseases. In recent years, the involvement of FSTL1 in cancer progression has been implicated and researched. FSTL1 plays a contradictory role in cancer, depending on the cancer type as well as the contents of the tumor microenvironment. As reviewed here, the structure and distribution of FSTL1 are first introduced. Subsequently, the expression and clinical significance of FSTL1 in various types of cancer as a tumor enhancer or inhibitor are addressed. Furthermore, we discuss the functional role of FSTL1 in various processes that involve tumor cell proliferation, metastasis, immune responses, stemness, cell apoptosis, and resistance to chemotherapy. FSTL1 expression is tightly controlled in cancer, and a multitude of cancer-related signaling cascades like TGF-ß/BMP/Smad signaling, AKT, NF-κB, and Wnt-ß-catenin signaling pathways are modulated by FSTL1. Finally, FSTL1 as a therapeutic target using monoclonal antibodies is stated. Herein, we review recent findings showing the double-edged characteristics and mechanisms of FSTL1 in cancer and elaborate on the current understanding of therapeutic approaches targeting FSTL1.

Physical activity and depression of Chinese college students: chain mediating role of rumination and anxiety.

Objective: To explore the relationship between physical activity and depression among college students, as well as the mediating role of rumination and anxiety. Methods: A total of 1,292 Chinese college students were investigated by physical activity questionnaire, rumination scale, self-rating anxiety scale (SAS), and depression scale. Results: (1) There was a significant negative correlation between physical activity and depression (r = -0.399, p < 0.01), and the direct path of physical activity on depression was significant (ß = -0.399, t = -13.374, p < 0.01). (2) Physical activity negatively predicted rumination (ß = -0.322, t = -10.440, p < 0.01) and anxiety (ß = -0.222, t = -7.089, p < 0.01). Rumination positively predicted anxiety (ß = 0.283, t = 9.017, p < 0.01) and depression (ß = 0.267, t = 9.046, p < 0.01). Anxiety positively predicted depression (ß = 0.262, t = 8.902, p < 0.01). (3) Rumination and anxiety play a significant mediating role between physical activity and depression. The mediating effect involves three paths: physical activity → rumination → depression (the mediating effect value: -0.076); physical activity → anxiety → depression (the mediating effect value: -0.052). Physical activity → rumination → anxiety → depression (the mediating effect value: -0.021). Conclusion: (1) Physical activity can negatively predict the rumination, anxiety, and depression of college students, which means physical activity can reduce rumination, anxiety, and depression of college students. (2) Physical activity can not only directly affect the depression of college students, but also indirectly affect depression through the independent intermediary role of rumination and anxiety, and the chain mediation of rumination and anxiety.

Exercise adherence and suicidal ideation of Chinese college students: a chain mediation model test.

Objective: The purpose of this study was to explore the relationship between exercise adherence and suicidal ideation in college students, as well as the mediating role of meaning in life and internet addiction. Methods: A total of 1925 college students (Mage = 19.51 years, SDage = 2.393 years) were recruited by stratified cluster sampling method in Zhaoqing University, among which 890 were males and 1,035 were females. Exercise adherence, meaning in life, internet addiction and suicidal ideation were assessed by using standard scales. Data were analyzed by Pearson Correlation Analysis, and bias-correction percentile Bootstrap method. Results: (1) There is a significant correlation between exercise adherence, meaning in life, internet addiction and suicide ideation; (2) meaning in life plays a significant mediating role between exercise adherence and suicidal ideation; internet addiction plays a significant mediating role between exercise adherence and suicidal ideation; meaning in life and internet addiction play a chain mediating role between exercise adherence and suicide ideation. Conclusion: Exercise adherence can not only directly predict college students' suicidal ideation, but also indirectly predict college students' suicidal ideation through the independent mediation and chain mediation of meaning in life and internet addiction.

Bioinformatics and experimental validation of an AURKA/TPX2 axis as a potential target in esophageal squamous cell carcinoma.

Aurora kinase A (AURKA), a serine/threonine kinase that regulates mitotic processes, has garnered significant interest given its association with the development of several types of cancer. In the present study, it was shown that AURKA expression was significantly upregulated in esophageal squamous cell carcinoma (ESCC) and could serve as a diagnostic and prognostic indicator based on data obtained from The Cancer Genome Atlas (TCGA) and immunohistochemical analysis. In addition, AURKA was functionally associated with ESCC cell proliferation and colony formation in vitro and knockdown of AURKA inhibited ESCC tumor growth in vivo. Both bioinformatics analysis and pull­down assays demonstrated that TPX2 interacted with AURKA, and their expression was correlated. AURKA cooperated with TPX2 to regulate ESCC progression via the PI3K/Akt pathway. Furthermore, AURKA or TPX2 expression levels were negatively associated with the infiltration of cytotoxic cells, CD8+ T cells and mast cells, but positively associated with Th2 cells. The present study provided a relatively comprehensive understanding of the oncogenic roles of AURKA in ESCC based on data obtained from TCGA combined with experimental analysis.

Effect of physical exercise on social adaptability of college students: Chain intermediary effect of social-emotional competency and self-esteem.

Objective: To explore the relationship between physical exercise and college students' social adaptability, as well as the mediating role of social-emotional competency and self-esteem. Methods: One thousand two hundred thirty college students were investigated by physical exercise questionnaire, social-emotional competency scale, self-esteem scale, and social adaptability scale. Data were analyzed by Pearson correlation analysis, structural equation model test and deviation-corrected percentile Bootstrap method. Results: (1) Physical exercise was positively correlated with social adaptability (r = 0.397, p < 0.01), and the direct path of physical exercise on social adaptability was significant (ß = 0.397, t = 15.174, p < 0.01). (2) Physical exercise positively predicted social-emotional competency (ß = 0.399, t = 15.235, p < 0.01) and self-esteem (ß = 0.305, t = 10.570, p < 0.01). Social-emotional competency positively predicted self-esteem (ß = 0.130, t = 4.507, p < 0.01) and social adaptability (ß = 0.169, t = 6.104, p < 0.01). Self-esteem positively predicted social adaptability (ß = 0.189, t = 6.957, p < 0.01). (3) Social-emotional competency and self-esteem play a significant mediating role between physical exercise and social adaptability. The mediating effect includes three paths: physical exercise→social-emotional competency→social adaptability (the mediating effect value: 0.068); physical exercise→self-esteem→social adaptability (the mediating effect value: 0.059). Physical exercise→social-emotional competency→self-esteem→social adaptability (the mediating effect value: 0.010). Conclusion: Physical exercise can not only directly affect social adaptability of college students, but also indirectly affect social adaptability through the independent intermediary role of social-emotional competency and self-esteem. Furthermore, physical exercise also affect social adaptability through the chain mediation of social-emotional competency and self-esteem.

Research on the relationship between physical activity, sleep quality, psychological resilience, and social adaptation among Chinese college students: A cross-sectional study.

Background: Sleep quality has become a frequent and prominent public health problem in Chinese universities, which seriously hinders the healthy development of college students and the improvement of the quality of higher education. Objective: The purpose of this study is to explore the relationship between physical activity and sleep quality among Chinese college students, and the mechanism of psychological resilience and social adaptation, and provide suggestions for improving the sleep quality among Chinese college students. Methods: From August to September 2022, a cross-sectional survey was conducted by using the convenience sampling method in Guangdong Province. 1,622 college students were investigated with Physical Activity Scale, Pittsburgh Sleep Quality Index Scale (PSQI), Psychological Resilience Scale, and Social Adaptation Diagnostic Scale, of which 893 were male and 729 were female. Use SPSS 23.0 and PROCESS plug-ins to analyze data. Results: (1) There was a significant negative correlation between physical activity and sleep quality (r = -0.237), and the direct path of physical activity to sleep quality was significant (ß = -0.236, t = -9.888, p < 0.01); (2) physical activity can positively predict psychological resilience (ß = 0.215, t = 8.823, p < 0.01) and social adaptation (ß = 0.164, t = 7.773, p < 0.01); psychological resilience can negatively predict sleep quality (ß = -0.337, t = -15.711, p < 0.01), positive prediction of social adaptation (ß = 0.504, t = 23.961, p < 0.01); social adaptation can negatively predict sleep quality (ß = -0.405, t = -18.558, p < 0.01); (3) psychological resilience and social adaptation play a significant mediating role between physical activity and sleep quality. The mediation effect consists of three paths: physical activity → psychological resilience → sleep quality (mediation effect value is -0.0723), physical activity → social adaptation → sleep quality (mediation effect value is -0.0662), and physical activity → psychological resilience → social adaptation → sleep quality (mediation effect value is -0.0438). (4) There is no gender difference in chain mediated effect. Conclusion: (1) Physical activity can significantly positively predict college students' psychological resilience and social adaptation, and negatively predict sleep quality, which means that physical activity may help improve college students' psychological resilience and social adaptation, and reduce sleep quality problems; (2) physical activity can not only directly affect the quality of sleep, but also indirectly affect the quality of sleep through the independent intermediary role of psychological resilience and social adaptation and the chain intermediary role of both. This further explains the reason why physical activity plays a role in college students' sleep quality, which will help to provide some inspiration for colleges and universities to reduce college students' sleep quality problems and formulate intervention plans.

Effect of physical exercise on sleep quality of college students: Chain intermediary effect of mindfulness and ruminative thinking.

The Physical Exercise Rating Scale, Mindfulness Attention Awareness Scale (MAAS), Ruminative Thinking Scale (RRS), and Pittsburgh Sleep Quality Index (PSQI) are used to conduct the questionnaire among a sample of 1,006 college students (average age = 19.95 years, SD = 1.86 years) to figure out whether there is any correlation between physical exercise and sleep quality in college students as well as how the mechanism of mindfulness and ruminative thinking plays a role in them. For data analysis, the Harman single-factor test was used; for the common method deviation test, Pearson's correlation analysis, and the mediating effect tested by using the bootstrap method were carried out. Results: (1) Overall, 34% (PSQI ≥ 8) of college students' sleep quality is poor. (2) The PSQI is positively correlated with ruminative thinking, while both are negatively correlated with the level of physical exercise and mindfulness; the level of physical exercise is positively correlated with the level of mindfulness. (3) Physical exercise can significantly negatively predict sleep quality (ß = -0.08, P < 0.05), significantly positively predict mindfulness (ß = 0.12, P < 0.001), and significantly negatively predict ruminative thinking (ß = -0.07, P < 0.05). When participate in physical exercise, mindfulness, and ruminative thinking enter the regression equation at the same time, only mindfulness and ruminative thinking can predict sleep quality(ß = -0.15, P < 0.001) significantly negatively predicted sleep quality and ruminative thinking (ß = 0.22, P < 0.001) significantly positively predicted sleep quality, while physical exercise (ß = -0.04, P > 0.05) had no significant predictive effect on sleep quality. (4) After controlling for age and gender, physical exercise appears to have an impact on sleep quality of college students through the independent intermediary role of mindfulness and ruminative thinking and the chain intermediary role of mindfulness and ruminative thinking, with a total mediating effect value of -0.007. This study reveals the relationship between physical exercise and sleep quality, as well as its mechanism, thus guiding college students to actively participate in physical exercise. It also provides corresponding suggestions to improve sleep quality as well as physical and mental health in college students.

The relationship between physical exercise and school adaptation of junior students: A chain mediating model.

Objective: This study explores the relationship between physical exercise and school adaptation of junior middle school students and constructs a chain intermediary model through the intermediary role of psychological resilience and sports learning motivation. Methods: Using the stratified cluster sampling method, 930 junior middle school students in Anhui Province were measured in group psychology by using the physical exercise rating scale, adolescent psychological resilience scale, physical learning motivation scale and school adaptation scale. The statistical software SPSS 23.0 and process plug-in were used for statistical processing, and the common method deviation test was carried out by Harman single-factor control method. Finally, the bootstrap sampling test method and process plug-in were used to test the significance of intermediary effect. Results: (1) The direct prediction effect of physical exercise on school adaptation is remarkable (t = 4.60, p < 0.01); (2) psychological resilience and sports learning motivation are the intermediary variables of the relationship between physical exercise and school adaptation; (3) psychological resilience and sports learning motivation play a chain mediation role in the relationship between physical exercise and school adaptation. The intermediary effect is composed of three indirect effects: physical exercise → psychological resilience → school adaptation (95% Cl: 0.004, 0.041), physical exercise → physical learning motivation → school adaptation (95% Cl:0.019, 0.065), physical exercise → psychological resilience → physical learning motivation → school adaptation (95% Cl:0.002, 0.021). Conclusions: Physical exercise can directly improve the school adaptation of junior middle school students, which can also affect junior middle school students' school adaptation indirectly through psychological resilience or sports learning motivation, and it can influence school adaptation through the chain mediation of psychological resilience and sports learning motivation.

The Relationship Between Physical Exercise and Prosocial Behavior of Junior Middle School Students in Post-Epidemic Period: The Chain Mediating Effect of Emotional Intelligence and Sports Learning Motivation and Gender Differences.

Purpose: This study examined the relationship between physical exercise (PE) and prosocial behavior (PSB) and constructed a chain mediation model through the mediating effect of physical education learning motivation (PELM) and emotional intelligence (EI). Methods: Through the stratified random sampling, 1053 students (average age = 14 years, SD = 0.96 years) that complied with the requirements were surveyed from Henan Province in China. PE, EI, PELM, and PSB were assessed using standard scales. For data analysis, Pearson's correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn. Results: (1) There was a significant positive correlation between PE and PSB (r = 0.137), and the direct path between PE and PSB was significant (ß = 0.09, t = 4.73, p < 0.01); (2) PE can positively predict EI (ß= 0.08, t = 5.27, p < 0.01) and PELM (ß= 0.04, t = 2.07, p < 0.05), EI can significantly and positively PSB (ß= 0.67, t = 22.12, p < 0.01), PELM can significantly and positively predict PSB (ß= 0.05, t =2.20, p<0.05); (3) EI and physical learning motivation play a significant intermediary role between PE and PSB. The mediating effect consists of three indirect effects: PE → EI → PSB (the mediating effect value is 0.055), PE → PELM → PSB (the mediating effect value is 0.002), PE → EI → PELM → PSB (the mediating effect value is 0.002); (4) The chain mediation effect is significant in girls, but not in boys. Conclusion: (1) PE can positively predict PSB. (2) EI and PELM had significant mediating effects between PE and PSB, including single mediating effects of EI and PELM and chain mediating effects of EI-PELM; (3) There are gender differences in the chain mediation effect.

The Relationship Between Exercise Intention and Exercise Behavior of Junior School Students: An Analysis of Chain Mediating Effect.

Objective: This study explores the relationship between exercise intention and exercise behavior and constructs a chain mediating model through the mediating effect of implementation intention and self-identity. Method: Through the stratified cluster sampling method, 1,573 junior school students (with an average age of 13.71 ± 0.891 years) were evaluated by the exercise intention scale, the implementation intention scale, the self-identity scale, and the physical exercise grade scale. For data analysis, the common method deviation test, Pearson correlation analysis, and Model 6 in the SPSS macro program compiled by Hayes for the chain mediating test were conducted. Results: (1) There is a marked correlation between positive exercise intention and exercise behavior (r = 0.345, p < 0.01), and exercise intention has a significant effect on the direct path of exercise behavior (ß = 0.162, t = 12.355, p < 0.01). (2) Exercise intention can positively predict implementation intention (ß = 0.219, t = 10.006, p < 0.01) and self-identity (ß = 0.160, t = 16.159, p < 0.01); implementation intention can significantly and positively predict exercise behavior (ß = 0.230, t = 12.742, p < 0.01),and self-identity can significantly and positively predict exercise behavior (ß = 0.273, t = 7.911, p < 0.01). (3) Implementation intention and self-identity play a significant mediating role between exercise intention and exercise behavior. The mediating effect consists of three indirect effects: exercise intention → implementation intention → exercise behavior (the mediating effect value is 0.050), exercise intention → self-identity → exercise behavior (the mediating effect value is 0.044), and exercise intention →implementation intention → self-identity → exercise behavior (the mediating effect value is 0.017). Conclusion: (1) Exercise intention can significantly and positively predict exercise behavior. (2) Implementation intention and self-identity exert a significant mediating effect between exercise intention and exercise behavior, including the separate mediating effect of implementation intention and self-identity, as well as the chain mediating effect of implementation intention and self-identity.

The Relationship Between Empowering Motivational Climate in Physical Education and Social Adaptation of Senior High School Students: An Analysis of Chain Mediating Effect.

This study aims to contribute to understanding the mechanisms underlying the association between empowering motivational climate in physical education and social adaptation among senior high school students, and has important implications for interventions that aim at improving social adaptation among senior high school students. Through the quota sampling, 1,526 students (average age = 17 years, SD = 0.714 years) who came from Anhui Province and met the requirements participated and completed the Empowering Motivational Climate Questionnaire in Physical Education (EMCQ-PE), the Physical Education Engagement Scale (PEES-S), the Emotional Intelligence Scale (EIS) (Chinese version), and the Adolescent Social Adaptation Assessment Questionnaire (ASAAQ). For data analysis, Pearson's correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn. The results showed that empowering motivational climate in physical education positively predicted social adaptation (ß = 0.282, p < 0.01), empowering motivational climate in physical education positively predicted physical education engagement and emotional intelligence (ß = 0.169, p < 0.01; ß = 0.690, p < 0.01), physical education engagement positively predicted emotional intelligence and social adaptation (ß = 0.591, p < 0.01; ß = 0.058, p < 0.05), and emotional intelligence positively predicted social adaptation (ß = 0.365, p < 0.01). Physical education engagement and emotional intelligence played a mediating role in empowering motivational climate in physical education and social adaptation, with a total mediating effect value of 0.251. This study shows that empowering motivational climate in physical education not only directly predicts social adaptation but also indirectly predicts social adaptation through the chain mediating effect of physical education engagement and emotional intelligence.

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model.

BACKGROUND: Vascular damage, autoimmune abnormalities, and fibrosis are the three pathological features of systemic sclerosis (SSc).However, pulmonary vascular damage is the main factor affecting the progression and prognosis of SSc. The main purpose of this study was to explore the molecular mechanism of Wenyang Huazhuo Tongluo Formula in alleviating pulmonary vascular injury in bleomycin-induced SSc mouse model. METHODS: Masson staining and H&E staining were used to analyze the degree of pulmonary vascular fibrosis and the infiltration of leukocyte cells in lung tissue ofbleomycin-induced SSc mouse models treated with saline (BLM group), Wenyang Huazhuo Tongluo Formula (WYHZTL group) and HIF-1α inhibitor KC7F2 (KC7F2 group). Blood vessel exudation was determined by analyzing the cell number and albumin concentration in bronchoalveolar lavage fluid using a cell counter and ELISA assay, respectively. The degree of vascular injury was assessed by measuring the expression levels of vWF, E-selectin, ICAM-1, VCAM-1, VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells using ELISA and immunofluorescence staining. Finally, the effect of Wenyang Huazhuo Tongluo Formula on the expression of HIF-1α was detected using immunofluorescence staining. RESULTS: Wenyang Huazhuo Tongluo Formula and KC7F2 significantly inhibited bleomycin-induced pulmonary vascular fibrosis and the level of perivascular inflammatory cell infiltration. The number of cells and the concentration of albumin were significantly reduced in the bronchoalveolar lavage fluid of the WYHZTL group and KC7F2 group compared with the BLM group. In addition, treatment with Wenyang Huazhuo Tongluo Formula and KC7F2 significantly downregulated the expression levels of vWF, E-selectin, ICAM-1, VCAM-1 and HIF-1α, but upregulated the expression of VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells, compared with treatment with saline. CONCLUSIONS: This study reveals that Wenyang Huazhuo Tongluo Formula plays a new role in the treatment of SSc by alleviating pulmonary vascular damage. Furthermore, we found that Wenyang Huazhuo Tongluo Formula alleviates pulmonary vascular injury and inhibits HIF-1α expression.

Identification of key genes and pathways related to cancer-associated fibroblasts in chemoresistance of ovarian cancer cells based on GEO and TCGA databases.

BACKGROUND: Studies have revealed the implications of cancer-associated fibroblasts (CAFs) in tumor progression, metastasis, and treatment resistance. Here, in silico analyses were performed to reveal the key genes and pathways by which CAFs affected chemoresistance in ovarian cancer. METHODS: Candidate genes were obtained from the intersected differentially expressed genes in ovarian cancer, ovarian cancer chemoresistance, and ovarian CAF-related microarrays and chemoresistance-related genes from GeneCards databases. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis were employed to identify the pathways engaged in ovarian cancer chemoresistance and ovarian CAF-related pathways. The top genes with high Degree in the protein-protein interaction network were intersected with the top genes enriched in the key pathways, followed by correlation analyses between key genes and chemotherapeutic response. The expression profiles of key genes were obtained from Human Protein Atlas database and TCGA-ovarian cancer data. RESULTS: p53, cell cycle, PI3K-Akt, and MAPK pathways were the key pathways related to the implication of CAFs in ovarian cancer chemoresistance. 276 candidate genes differentially expressed in CAFs were associated with ovarian cancer chemoresistance. MYC, IGF1, HRAS, CCND1, AKT1, RAC1, KDR, FGF2, FAS, and EGFR were enriched in the key chemoresistance-related ways. Furthermore, MYC, EGFR, CCND1 exhibited close association with chemotherapeutic response to platinum and showed a high expression in ovarian cancer tissues and platinum-resistant ovarian cancer cells. CONCLUSION: The study suggests the key genes (MYC, EGFR, and CCND1) and pathways (p53, cell cycle, PI3K-Akt, and MAPK) responsible for the effect of CAFs on ovarian cancer chemoresistance.

Th17 cell-derived miR-155-5p modulates interleukin-17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis.

BACKGROUND: miR-155-5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)-17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR-155-5p in the regulation of IL-17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression. METHODS: Th17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT-qPCR and western blotting were used to examine the expression patterns of miR-155-5p, IL-17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR-155-5p. RNA pull-down assays were performed to detect the interaction of IL-17 and SOCS1 with miR-155-5p. In situ hybridization was performed to analyze the co-expression pattern of miR-155-5p and IL17A in Th17 cells. RESULTS: The levels of Th17 cell-derived miR-155-5p were significantly up-regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR-155-5p positively regulated IL-17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR-155-5p. The binding status of IL-17 and SOCS1 to miR-155-5p was related to SSc progression. An increase in the co-localization of miR-155-5p and IL-17 was associated with greater SSc progression. CONCLUSIONS: IL-17 and SOCS1 expression modulated by Th17 cell-derived miR-155-5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.

The Relationship Between Physical Exercise and Mobile Phone Addiction Tendency of University Students in China: A Moderated Mediation Model.

This study aims to explore the relationship between physical exercise (PE), self-control (SC), physical exercise atmosphere (PEA), and mobile phone addiction tendency (MPAT) among Chinese university students. Through the quota sampling, 1,433 students complied with the requirements were surveyed from 10 universities in China. PE, SC, PEA, and MPAT were assessed using standard scales. For data analysis, common method deviation test, mean number, standard deviation, correlation analysis and structural equation model analysis were carried out in turn. The results showed PE and MPAT were negatively related (r = -0.158, p < 0.05); PE significantly positively predicted SC (ß = 0.082, t = 3.748, p < 0.01), and SC significantly negatively predicted MPAT (ß = -0.743, t = -19.929, p < 0.01). Bootstrap method was used to test the mediating effect of SC. The results showed that 95% confidence interval did not include 0. After adding the mediating variable of SC, PE did not significantly negatively predict the tendency of MPAT (ß = -0.027, t = -1.257, p > 0.05). The interaction item PEA and SC could significantly positively predict the tendency of MPAT (ß = 0.165, t = 2.545, p < 0.05). In the high PEA group, SC had a significant negative predictive effect on the tendency of MPAT (ß = -0.665, t = -14.408, p < 0.01); However, in the low PEA group, the negative predictive effect was stronger (ß = -0.834, t = -15.015, p < 0.01). The present study shows that PE significantly negatively predicted the tendency of MPAT, and SC played a complete mediating role in the relationship between PE and MPAT; The second half of the indirect effect of PE and MPAT was regulated by the PEA. The PEA will enhance the influence of SC on MPAT, but the high PEA will increase the level of MPAT of individuals at a very high level of SC.

The relationship between physical exercise and subjective well-being among Chinese junior high school students: A chain mediating model.

Objective: This study aims to help understand the mechanism behind the relationship between physical exercise and the subjective well-being among Chinese junior high school students, and it is of great significance for the intervention measures to improve the subjective well-being of junior high school students. Methods: Using stratified cluster sampling method, 1,510 junior high school students (727 males and 783 females) were measured by physical exercise rating scale, perceived social support scale, physical exercise self-efficacy scale, and subjective well-being scale. For data analysis, Pearson's correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn. Results: Common method biases can be accepted in this study. (1) There is a positive correlation between physical exercise and subjective well-being, and physical exercise has a significant predictive effect on subjective well-being(ß = 0.367 t = 9.415 p < 0.01); (2) Perceived social support partially mediated the relationship between physical exercise and subjective well-being (ß = 0.08, t = 3.083, p < 0.01), and its effect ratio is 78.047%; (3) Physical exercise self-efficacy plays a partial mediating role between physical exercise and subjective well-being(ß = 0.181, t = 5.132, p < 0.01), accounting for 50.632%; (4) The chain mediating effect of perceived social support and physical exercise self-efficacy was significant (the mediating effect value was 0.028), and the effect amount was 7.629%. Conclusion: (1) Physical exercise can significantly positively predict the subjective well-being of junior high school students; (2) Physical exercise can also indirectly affect the subjective well-being of junior high school students through the mediating effect of perceived social support and physical exercise self-efficacy. The intermediary effect includes three paths, namely, the individual intermediary effect of perceived social support and physical exercise self-efficacy and the chain intermediary effect of perceived social support physical exercise self-efficacy.

The Relationship Between Empowering Motivational Climate in Physical Education and Social Responsibility of High School Students: Chain Mediating Effect Test.

Objective: This study aimed to contribute to understanding the mechanisms underlying the association between empowering motivational climate in physical education and social responsibility among high school students, and have important implications for interventions aimed at improving social responsibility among high school students. Methods: Through the quota sampling, 802 students (average age = 17 years, SD = 0.97 years) that complied with the requirements were surveyed from Anhui Province in China. Empowering motivational climate in physical education, social responsibility, interpersonal disturbance, and general self-efficacy were assessed using standard scales. For data analysis, Pearson's correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn. Results: (1) Common method biases can be accepted in this study, and the correlation among empowering motivational climate in physical education, social responsibility, interpersonal disturbance, and general self-efficacy are all significant; (2)Empowering motivational climate in physical education, interpersonal disturbance and general self-efficacy can all predict social responsibility significantly; (3) Structural equation modeling indicates good fit: χ2/df = 2.86, RMESA = 0.068, CFI = 0.92, NNFI = 0.91, NFI = 0.90, GFI = 0.93. It indicates that interpersonal disturbance and general self-efficacy can play mediating roles between empowering motivational climate in physical education and social responsibility, respectively. After that, interpersonal disturbance as well as general self-efficacy in turn plays the chain mediating effect in the relationship between empowering motivational climate in physical education and social responsibility. The effect size of the mediating effect of interpersonal disturbance and general self-efficacy in the relationship between empowering motivational climate in physical education and social responsibility is 0.048 and 0.148, respectively, and the effect size of the chain mediating effect is 0.031. Conclusion: Empowering motivational climate in physical education not only has a direct effect on social responsibility among high school students, but also influences social responsibility by the chain mediating effect of interpersonal disturbance and general self-efficacy.

A novel tumor suppressor SPINK5 targets Wnt/ß-catenin signaling pathway in esophageal cancer.

Esophageal cancer is one of the most common tumor in the world, and the morbidity rate is as high as 100/100 000 in some parts of China. Therefore, it is important and urgent to explore the pathogenesis of esophageal cancer and find new therapeutic targets for esophageal cancer. In this study, we found that a novel tumor suppressor SPINK5 is significantly reduced in the development of esophageal cancer, and is closely related to the pathological differentiation and lymph node metastasis of esophageal cancer via bioinformatics analysis and esophageal cancer tissue array. Further studies have found that SPINK5 is closely related to Wnt/ß-catenin signaling pathway by bioinformatics analysis and western blot. In esophageal cancer cells, SPINK5 overexpression can inhibit Wnt/ß-catenin signaling pathway. Combined with LiCl or MG-132 treatment, SPINK5 can inhibit GSK3ß phosphorylation and promote ß-catenin protein degradation, thus inhibit Wnt/ß-catenin signaling pathway. In vivo study, SPINK5 overexpression can significantly inhibit the growth of esophageal cancer cells. Our study shows that SPINK5 can inhibit the proliferation, migration, and invasion of esophageal cancer cells by inhibiting Wnt/ß-catenin signaling pathway, and thus plays an important role in the development of esophageal cancer, and may serve as a treatment target of esophageal cancer.