Background: Living arrangements have impact on life satisfaction among older adults. However, the mechanism how it works has received less attention. This study aims to examine the mediating role of meaning in life and social support in the relationship between living arrangements and life satisfaction. Methods: A total of 215 older adults from nine nursing homes and three communities were included in this study. The Social Support Rating Scale, Meaning in Life Questionnaire and Life Satisfaction Index A were adopted. Data were analyzed with Hayes' s bias-corrected bootstrapping method.Results: Both social support and presence of meaning in life had positive correlations with life satisfaction (p< 0.001), and they were significant mediators between living arrangements and life satisfaction (p<0.01). Conclusion: To improve the life satisfaction of nursing home residents, more emphasis should be placed on encouraging residents to seek or maintain a meaningful life and creating a more positive climate of social support.
Background Abnormal proliferation and migration of cells are hallmarks of cancer initiation and malignancy. Asparagine endopeptidase (AEP) has specific substrate cleavage ability and plays a pro-cancer role in a variety of cancers. However, the underlying mechanism of AEP in cancer proliferation and migration still remains unclear. Methods Co-immunoprecipitation and following mass spectrometry were used to identify the substrate of AEP. Western blotting was applied to measure the expression of proteins. Single cell/nuclear-sequences were done to detect the heterogeneous expression of Tmod3 in tumor tissues. CCK-8 assay, flow cytometry assays, colony formation assay, Transwell assay and scratch wound-healing assay were performed as cellular functional experiments. Mouse intracranial xenograft tumors were studied in in vivo experiments. Results Here we showed that AEP cleaved a ubiquitous cytoskeleton regulatory protein, tropomodulin-3 (Tmod3) at asparagine 157 (N157) and produced two functional truncations (tTmod3-N and tTmod3-C). Truncated Tmod3 was detected in diverse tumors and was found to be associated with poor prognosis of high-grade glioma. Functional studies showed that tTmod3-N and tTmod3-C enhanced cancer cell migration and proliferation, respectively. Animal models further revealed the tumor-promoting effects of AEP truncated Tmod3 in vivo. Mechanistically, tTmod3-N was enriched in the cell cortex and competitively inhibited the pointed-end capping effect of wild-type Tmod3 on filamentous actin (F-actin), leading to actin remodeling. tTmod3-C translocated to the nucleus, where it interacted with Staphylococcal Nuclease And Tudor Domain Containing 1 (SND1), facilitating the transcription of Ras Homolog Family Member A/Cyclin Dependent Kinases (RhoA/CDKs). Conclusion The newly identified AEP-Tmod3 protease signaling axis is a novel “dual-regulation” mechanism of tumor cell proliferation and migration. Our work provides new clues to the underlying mechanisms of cancer proliferation and invasive progression and evidence for targeting AEP or Tmod3 for therapy.
BackgroundGlioblastoma (GBM) is the most common malignant primary brain tumor, which associated with extremely poor prognosis.MethodsData from datasets GSE16011, GSE7696, GSE50161, GSE90598 and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) between patients and controls. DEGs common to all five datasets were analyzed for functional enrichment and for association with overall survival using Cox regression. Candidate genes were further screened using least absolute shrinkage and selection operator (LASSO) and random forest algorithms, and the effects of candidate genes on prognosis were explored using a Gaussian mixed model, a risk model, and concordance cluster analysis. We also characterized the GBM landscape of immune cell infiltration, methylation, and somatic mutations.ResultsWe identified 3,139 common DEGs, which were associated mainly with PI3K-Akt signaling, focal adhesion, and Hippo signaling. Cox regression identified 106 common DEGs that were significantly associated with overall survival. LASSO and random forest algorithms identified six candidate genes (AEBP1, ANXA2R, MAP1LC3A, TMEM60, PRRG3 and RPS4X) that predicted overall survival and GBM recurrence. AEBP1 showed the best prognostic performance. We found that GBM tissues were heavily infiltrated by T helper cells and macrophages, which correlated with higher AEBP1 expression. Stratifying patients based on the six candidate genes led to two groups with significantly different overall survival. Somatic mutations in AEBP1 and modified methylation of MAP1LC3A were associated with GBM.ConclusionWe have identified candidate genes, particularly AEBP1, strongly associated with GBM prognosis, which may help in efforts to understand and treat the disease.
Objective Cervical cerclage is effective in prolonging the number of weeks gestation in patients with cervical insufficiency(CI). However, valuable predictors with successful cervical cerclage remain limited. It aimed to evaluate the value of the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the outcomes of cervical cerclage. Methods This study analyzed 374 participants. Inflammatory markers were calculated using maternal peripheral blood. The association of inflammatory markers and the outcome of cervical cerclage were analyzed. And the optimal cut-off values of inflammatory markers were calculated. Also, the Chi-square test and logistic and linear regression analyses were performed to evaluate inflammatory markers with the maternal outcome and neonatal outcomes. Results 374 pregnancies were included in this study. Finally, 268 (71.7%) participants suffered successful cervical cerclage. This study demonstrated that the baseline BMI (cm 2 /kg), the bulging membrane, cervical dilation (≥2cm), the amniotic sac herniation, the neutrophils counts, the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were significant difference between the successful and unsuccessful groups (all P<0.05). Additionally, maternal blood inflammatory markers, such as WBC, lymphocyte, neutrophils, monocyte, platelet counts, SII, and SIRI, were significantly associated with maternal-neonatal outcomes. Furthermore, the results demonstrated that the SII level had the highest OR (OR=4.626; 95% CI (2.500–8.560)), as well as the following: SIRI level (OR = 3.795; 95% CI (1.989–7.242)), cervical dilation (≥2cm) (OR =3.477; 95% CI (1.458–10.844)), and amniotic sac herniation (OR = 1.796; 95% (0.473–4.975)). Conclusion This study demonstrated that the baseline SII level and SIRI level are important biochemical markers for predicting the outcome of cervical cerclage and maternal-neonatal outcomes with non-invasive procedures. They can help to provide personalized treatment before surgery and enhance postoperative surveillance.
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