The difference of affect improvement effect of music intervention in aerobic exercise at different time periods

Objectives: A randomized controlled experimental design that combines exercise and music intervention was adopted in this study to verify whether this approach could help improve human affect. The differences in the effect of music listening on affective improvement were compared in four different periods: before, during, and after aerobic power cycling exercise and the whole exercise course.Method: A total of 140 subjects aged 19–30 years (average age: 23.6 years) were recruited and randomly divided into four music intervention groups, namely, the pre-exercise, during-exercise, post-exercise, and the whole-course groups. The subjects’ demographic and sociological variables and daily physical activities were collected using questionnaires. Individual factors, such as the subjects’ noise sensitivity, personality traits, and degree of learning burnout, were collected via scale scoring. A laboratory in Zhejiang Normal University was selected as the experimental site. The testing procedure can be summarized as follows. In a quiet environment, the subjects were asked to sit quietly for 5 min after completing a preparation work, and then they were informed to take a pre-test. The four subject groups wore headphones and completed 20 min of aerobic cycling (i.e., 7 min of moderate-intensity cycling [50%*HRR + RHR] + 6 min of low-intensity interval cycling [30%*HRR + RHR] + 7 min of moderate-intensity cycling [50%*HRR + RHR] after returning to a calm state (no less than 20 min) for post-testing. The affect improvement indicators (dependent variables) collected in the field included blood pressure (BP), positive/negative affect, and heart rate variability indicators (RMSSD, SDNN, and LF/HF).Results: 1) Significant differences were found in the participants’ systolic BP (SBP) indices and the effect of improvement of the positive affect during the exercise–music intervention among the four groups at different durations for the same exercise intensity (F = 2.379, p = 0.030, ɳp2 = 0.058; F = 2.451, p = 0.043, ɳp2 = 0.091). 2) Music intervention for individuals during exercise contribute more to the reduction of SBP than the other three time periods (F = 3.170, p = 0.047, ɳp2 = 0.068). Improvement in the participants’ negativity affective score was also better during exercise, and it was significantly different than the other three time periods (F = 5.516, p = 0.006, ɳp2 = 0.113). No significant differences were found in the improvement effects of the other effective indicators for the four periods.Conclusion: Exercise combined with music intervention has a facilitative effect on human affect improvement, and listening to music during exercise has a better impact on affective improvement than music interventions at the other periods. When people perform physical activities, listening to music during exercise positively affects the progress effect among them

KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker

Background: KIAA1199 has been considered a key regulator of carcinogenesis. However, the relationship between KIAA1199 and immune infiltrates, as well as its prognostic value in lung adenocarcinoma (LUAD) remains unclear.Methods: The expression of KIAA1199 and its influence on tumor prognosis were analyzed using a series of databases, comprising TIMER, GEPIA, UALCAN, LCE, Prognoscan and Kaplan-Meier Plotter. Further, immunohistochemistry (IHC), western blot (WB) and receiver operating characteristic (ROC) curve analyses were performed to verify our findings. The cBioPortal was used to investigate the genomic alterations of KIAA1199. Prediction of candidate microRNA (miRNAs) and transcription factor (TF) targeting KIAA1199, as well as GO and KEGG analyses, were performed based on LinkedOmics. TIMER and TISIDB databases were used to explore the relationship between KIAA1199 and tumor immune infiltration.Results: High expression of KIAA1199 was identified in LUAD and Lung squamous cell carcinoma (LUSC) patients. High expression of KIAA1199 indicated a worse prognosis in LUAD patients. The results of IHC and WB analyses showed that the expression level of KIAA1199 in tumor tissues was higher than that in adjacent tissues. GO and KEGG analyses indicated KIAA1199 was mainly involved in extracellular matrix (ECM)-receptor interaction and extracellular matrix structure constituent. KIAA1199 was positively correlated with infiltrating levels of CD4+ T cells, macrophages, neutrophil cells, dendritic cells, and showed positive relationship with immune marker subsets expression of a variety of immunosuppressive cells.Conclusion: High expression of KIAA1199 predicts a poor prognosis of LUAD patients. KIAA1199 might exert its carcinogenic role in the tumor microenvironment via participating in the extracellular matrix formation and regulating the infiltration of immune cells in LUAD. The results indicate that KIAA1199 might be a novel biomarker for evaluating prognosis and immune cell infiltration in LUAD

BERBERINE INDUCES AUTOPHAGY, APOPTOSIS AND MODULATES MIR-155 IN HEAD AND NECK SQUAMOUS CARCINOMA CELLS.

Berberine (BBR) an active natural plant alkaloid extracted from Coptidis rhizoma, displays potent anticancer activity over a variety of cancer cell lines. The cytotoxic activity of BBR in cancer cells is attributed to persuade, programmed cell death characterized by the release of cytochrome c, accompanied by activation of caspase-3 and caspase-9. In the present study, we evaluated BBR significantly reduces the cell viability and clonogenic property of head and neck squamous carcinoma (HNSC) cells. Our results revealed that BBR simultaneously induces apoptosis and autophagy in HNSC cells. Mechanistically, BBR induces autophagy in HNSC cells which were confirmed by acridine orange (AO) staining by visualization of prominent orange red color acidic autophagosomes in the cytoplasm. However, immunoblotting shows the steady conversion of MAP-LC-3I to LC-3II with concomitant degradation of autophagy substrate protein SQSTM1/p62. Annexin V FITC staining analysis by flow cytometry revealed a significant induction of apoptosis at higher doses of BBR. Furthermore, the immunoblotting analysis revealed a prominent cleavage of proapoptotic proteins procaspase-3 and PARP1 at higher doses of BBR. Additionally, we found significant upregulation and downregulation of tumor suppressor microRNA-155 (miR-155) and oncogenic miR-21 respectively, when HNSC cells were exposed to higher doses of BBR. In conclusion, these results demonstrate that BBR exhibits a significant anti-proliferative effect with the simultaneous induction of autophagy and apoptosis and modulates miRNA expression in HNSC cells

GSDMD knockdown attenuates phagocytic activity of microglia and exacerbates seizure susceptibility in TLE mice

Abstract Background Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Phagocytic activity of microglia is essential for clearing apoptotic neuronal debris, allowing for repair and regeneration. Our previous research has shown that gasdermin D (GSDMD)-mediated pyroptosis is involved in the pathogenesis of TLE. However, whether GSDMD-mediated pyroptosis influences the accumulation of apoptotic neurons remains unclear. Therefore, the present study was designed to investigate whether phagocytic activity of microglia is involved in GSDMD-mediated pyroptosis and the pathogenesis of TLE. Methods To establish a TLE model, an intra-amygdala injection of kainic acid (KA) was performed. The Racine score and local field potential (LFP) recordings were used to assess seizure severity. Neuronal death in the bilateral hippocampus was assessed by Nissl staining and TUNEL staining. Microglial morphology and phagocytic activity were detected by immunofluorescence and verified by lipopolysaccharide (LPS) and the P2Y12R agonist 2MeSADP. Results GSDMD knockdown augmented the accumulation of apoptotic neurons and seizure susceptibility in TLE mice. Microglia activated and transition to the M1 type with increased pro-inflammatory cytokines. Furthermore, GSDMD knockdown attenuated the migration and phagocytic activity of microglia. Of note, LPS-activated microglia attenuated seizure susceptibility and the accumulation of apoptotic neurons in TLE after GSDMD knockdown. A P2Y12R selective agonist, 2MeSADP, enhanced the migration and phagocytic activity of microglia. Conclusions Our results demonstrate that GSDMD knockdown exacerbates seizure susceptibility and the accumulation of apoptotic neurons by attenuating phagocytic activity of microglia. These findings suggest that GSDMD plays a protective role against KA-induced seizure susceptibility

High Vimentin Expression Predicts a Poor Prognosis and Progression in Colorectal Cancer: A Study with Meta-Analysis and TCGA Database

The aim of this study was to evaluate the role of vimentin expression in the prognosis and progression of CRC. Meta-analysis was conducted to investigate the correlations between vimentin and prognosis and clinicopathological features in CRC. Literatures were searched by PubMed, Embase, ClinicalKey, CNKI, VIP, and WanFang databases. The Cancer Genome Atlas (TCGA) database was used to assess the association of vimentin expression with survival rate in CRC. Eleven reports with 1969 cases were included in the meta-analysis. The results showed that positive vimentin expression predicted a poor overall survival (OS) in the univariate analysis (HR: 2.087, 95%CI: 1.660-2.625) and multivariate analysis (HR: 1.633, 95%CI: 1.223-2.181). Vimentin overexpression also conferred worse disease-free survival (DFS) in the univariate analysis (HR: 2.069, 95%CI: 1.024-4.179) and multivariate analysis (HR: 2.802, 95%CI: 1.421-5.527). Moreover, upregulated vimentin is related to lymph node metastasis (OR: 2.288, 95%CI: 1.159-4.517), TNM stages (OR: 1.957, 95%CI: 1.333-2.873), and N stage (OR: 2.316, 95%CI: 1.482-3.620). Analysis of TCGA database indicated that elevated vimentin predicated a shorter OS (p=0.033). Our findings reveal that upregulated vimentin contributes to the progression and poor prognosis of CRC. Vimentin may be a prognostic biomarker and therapeutic target in patients with CRC

COVID‐19 and Anticoagulation for Atrial Fibrillation: An Analysis of US Nationwide Pharmacy Claims Data

Background Adherence to oral anticoagulation (OAC) is critical for stroke prevention in atrial fibrillation. However, the COVID‐19 pandemic may have disrupted access to such therapy. We hypothesized that our analysis of a US nationally representative pharmacy claims database would identify increased incidence of lapses in OAC refills during the COVID‐19 pandemic. Methods and Results We identified individuals with atrial fibrillation prescribed OAC in 2018. We used pharmacy dispensing records to determine the incidence of 7‐day OAC gaps and 15‐day excess supply for each 30‐day interval from January 1, 2019 to July 8, 2020. We constructed interrupted time series analyses to test changes in gaps and supply around the pandemic declaration by the World Health Organization (March 11, 2020), and whether such changes differed by medication (warfarin or direct OAC), prescription payment type, or prescriber specialty. We identified 1 301 074 individuals (47.5% women; 54% age ≥75 years). Immediately following the COVID‐19 pandemic declaration, we observed a 14% decrease in 7‐day OAC gaps and 56% increase in 15‐day excess supply (both P<0.001). The increase in 15‐day excess supply was more marked for direct OAC (69% increase) than warfarin users (35%; P<0.001); Medicare beneficiaries (62%) than those with commercial insurance (43%; P<0.001); and those prescribed OAC by a cardiologist (64%) rather than a primary care provider (48%; P<0.001). Conclusions Our analysis of nationwide claims data demonstrated increased OAC possession after the onset of the COVID‐19 pandemic. Our findings may have been driven by waivers of early refill limits and patients’ tendency to stockpile medications in the first weeks of the pandemic