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Mechanistically, ChIP assay and luciferase reporter assay revealed that BMAL1 bound to the promoter of and activate the transcription of Gli2, but not Gli1, suggesting that the involvement of Bmal1 in renal fibrosis was possibly mediated via Gli2-dependent mechanisms. Furthermore, treatment with TGF-β increased Bmal1 in cultured murine proximal tubular cells. Knockdown of Bmal1 abolished, while overexpression of Bmal1 increased, Gli2 and the expression of fibrosis-related genes. Collectively, these results revealed a prominent role of the core clock gene Bmal1 in tubulointerstitial fibrosis. Moreover, we identified Gli2 as a novel target of Bmal1, which may mediate the adverse effect of Bmal1 in obstructive nephropathy.
Evidence indicates that emotions such as anger are associated with increased incidence of sudden cardiac death, but the biological mechanisms remain unclear. We tested the hypothesis that, in patients with sudden death vulnerability, anger would be associated with arrhythmic vulnerability, indexed by cardiac repolarization instability.
Patients with coronary artery disease (CAD) and an implantable cardioverter defibrillator (ICD; n=41) and healthy controls (n=26) gave an anger-inducing speech (anger recall), rated their current (state) anger, and completed measures of trait (chronic) levels of Anger and Hostility. Repolarization instability was measured using QT Variability Index (QTVI) at resting baseline and during anger recall using continuous ECG.
ICD patients had significantly higher QTVI at baseline and during anger recall compared with controls, indicating greater arrhythmic vulnerability overall. QTVI increased from baseline to anger recall to a similar extent in both groups. In ICD patients but not controls, during anger recall, self-rated anger was related to QTVI (r=.44, p=.007). Trait (chronic) Anger Expression (r=.26, p=.04), Anger Control (r=-.26, p=.04), and Hostility (r=.25, p=.05) were each associated with the change in QTVI from baseline to anger recall (ΔQTVI). see more Moderation analyses evaluated whether psychological trait associations with ΔQTVI were specific to the ICD group. Results indicated that Hostility scores predicted ΔQTVI from baseline to anger recall in ICD patients (β=0.07, p=.01), but not in controls.
Anger increases repolarization lability, but in patients with CAD and arrhythmic vulnerability, chronic and acute anger interact to trigger cardiac repolarization lability associated with susceptibility to malignant arrhythmias.
Anger increases repolarization lability, but in patients with CAD and arrhythmic vulnerability, chronic and acute anger interact to trigger cardiac repolarization lability associated with susceptibility to malignant arrhythmias.
The coronavirus disease-2019 (COVID-19) outbreak has presented unique dermatologic challenges due to respiratory protective equipment (RPE)-related skin conditions.
To objectively evaluate the effects of RPE including medical masks and respirators on the skin barrier by measuring various physiological properties of the skin.
A cross-sectional study was designed. Twenty healthy healthcare workers were included in this study. Skin parameters including skin hydration, transepidermal water loss (TEWL), erythema, sebum secretion, pH, and skin temperature were measured in the RPE-covered and RPE-uncovered areas of the face 4 and 8 hours after wearing RPE and 14 hours after not wearing RPE.
Skin hydration, TEWL, erythema, pH, and skin temperature increased in the RPE-covered areas after wearing RPE for 4 and 8 hours. By contrast, in the RPE-uncovered areas, skin hydration decreased and TEWL, erythema, and pH showed minimal changes over time. Based on the repeated-measure analysis, the changes in skin physiological properties over time were significantly different between RPE-covered and RPE-uncovered areas.
We observed that skin physiological characteristics change with the prolonged use of RPE such as medical masks and respirators. These changes may lead to various adverse skin reactions after long-term use.
We observed that skin physiological characteristics change with the prolonged use of RPE such as medical masks and respirators. These changes may lead to various adverse skin reactions after long-term use.Hypoxia is a common feature of tumor microenvironment (TME), which promotes tumor progression, metastasis and therapeutic drug resistance via a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of hepatocellular carcinoma (HCC). From a genome-wide CRISPR/Cas9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion, and consequently inhibits tumor growth. Supplementation of lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by HIF-1α and FTO-mediated m6A modification through transcriptional and post-transcriptional regulation, respectively. Analysis of TCGA shows that elevated levels of ALDOA are significantly correlated with poor prognosis of HCC patients. In a screen of FDA-approved drugs based on structured hierarchical virtual platforms, we identify sulfamonomethoxine derivative cpd-5 as a potential inhibitor to target ALDOA, evidenced by the anti-tumor activity of cpd-5 in preclinical patient-derived xenograft models of HCC. CONCLUSION Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in hypoxic TME is a promising therapeutic strategy for treating HCC.
Intercropping, which is growing two or more different crops in the same field simultaneously, is an effective traditional agricultural practice for productivity, resource utilization, and pest control. However, study on intercropping in paddy fields is limited. So in this study, field experiments of 2 years/four seasons (early and late seasons in 2016 and 2017) were conducted to examine the effects of rice-Pontederia cordata intercropping on rice plant growth, pest control, yield, income, and grain quality.
We found rice-P. cordata intercropping significantly decreased the occurrence of rice diseases and pests, with a 22.0-45.9% reduction in sheath blight and a 33.8-34.4% reduction in leaf folders. The mean land equivalent ratio (LER) (1.09) result indicates that intercropping rice and P. cordata generated positive yield effects. In addition, due to the economic profit from the replacement stripe of P. cordata in the rice paddy field, intercropping rice with P. cordata could greatly enhance farmer income.
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