Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was ...limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.
Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low ...5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.
Myocardial fibrosis after myocardial infarction (MI) is a leading cause of heart diseases. MI activates cardiac fibroblasts (CFs) and promotes CF to myofibroblast transformation (CMT). This study ...aimed to investigate the role of miR‐21 in the regulation of CMT and myocardial fibrosis. Primary rat CFs were isolated from young SD rats and treated with TGF‐β1, miR‐21 sponge or Jagged1 siRNA. Cell proliferation, invasion and adhesion were detected. MI model was established in male SD rats using LAD ligation method and infected with recombinant adenovirus. The heart function and morphology was evaluated by ultrasonic and histological analysis. We found that TGF‐β1 induced the up‐regulation of miR‐21 and down‐regulation of Jagged1 in rat CFs. Luciferase assay showed that miR‐21 targeted 3′‐UTR of Jagged1 in rat CFs. miR‐21 sponge inhibited the transformation of rat CFs into myofibroblasts, and abolished the inhibition of Jagged1 mRNA and protein expression by TGF‐β1. Furthermore, these effects of miR‐21 sponge on rat CFS were reversed by siRNA mediated knockdown of Jagged1. In vivo, heart dysfunction and myocardial fibrosis in MI model rats were partly improved by miR‐21 sponge but were aggravated by Jagged1 knockdown. Taken together, these results suggest that miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1. miR‐21 and Jagged1 are potential therapeutic targets for myocardial fibrosis.
Background and Purpose
Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were ...cardioprotective in age‐related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown.
Experimental Approach
We determined the effects of spermidine in a model of MI, Sprague–Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots.
Key Results
Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post‐MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway.
Conclusions and Implications
Our findings suggest that spermidine improved MI‐induced cardiac dysfunction by promoting AMPK/mTOR‐mediated autophagic flux.
Purpose
During myocardial infarction (MI), cardiac fibroblasts (CFs) transform into myofibroblast (CMT). This study aimed to investigate the crosstalk of Notch1 and transforming growth factor‐β1 ...(TGF‐β1)/Smad3 signaling in the regulation of CMT and myocardial fibrosis.
Methods
Primary CFs were isolated from young rats and treated with TGF‐β1 or adenovirus to overexpress or knockdown Notch1 intracellular domain (N1ICD) or Smad3.
Results
TGF‐β1 decreased the expression of fibroblast markers but increased the expression of myofibroblast markers in rat CFs. TGF‐β1 increased the proliferation, invasion, and adhesion, and the secretion of collagen I of CFs, and these effects were inhibited by N1ICD overexpression. Moreover, endogenous Smad3 phosphorylation in CFs was enhanced by N1ICD knockdown, whereas TGF‐β1 induced Smad3 phosphorylation was antagonized by the N1ICD overexpression. Conversely, endogenous N1ICD activation in CFs was antagonized by Smad3, whereas TGF‐β1 induced N1ICD inactivation was antagonized by Smad3 knockdown. Coimmunoprecipitation showed that N1ICD interacted with Smad3 and immunostaining revealed the colocalization of N1ICD and Smad3 in the nuclei of CFs. Moreover, we demonstrated the functional antagonism of N1ICD and Smad3 on the phenotypes of CFs. Finally, TGF‐β1/Smad3 signaling promoted whereas Notch signaling inhibited myocardial fibrosis in rat MI model.
Conclusion
Notch signaling inhibits CMT by antagonizing TGF‐β1/Smad3 signaling. Notch signaling activators and TGF‐β1/Smad3 signaling inhibitors could be exploited for therapeutic intervention to inhibit myocardial fibrosis after MI.
N1ICD interacted with Smad3 and immunostaining revealed the colocalization of N1ICD and Smad3 in the nuclei of cardiac fibroblasts.
N1ICD and Smad3 antagonized each other to regulate the phenotypes of cardiac fibroblasts.
TGF‐β1/Smad3 signaling promoted but Notch signaling inhibited myocardial fibrosis in the rat model.
Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the ...myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad‐N1ICD and Ad‐shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.
Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.
•Frontline medical workers had higher rates of anxiety, depressed mood and insomnia than non-frontline medical workers.•No significant difference in help-seeking and treatment behaviors between ...frontline and non-frontline medical workers.•The timely mental support and intervention should be provided for medical workers, especially for those on the frontline.
Coronavirus disease 2019 (COVID-19) is a new infectious disease with high transmissibility and morbidity. It has caused substantial mental distress to medical professionals. We aimed to compare the psychological impact of the COVID-19 outbreak between frontline and non-frontline medical workers in China.
This case-control study recruited 1173 frontline and 1173 age- and sex-matched non-frontline medical workers during the COVID-19 outbreak (February 11 to 26, 2020). A set of online questionnaires were used to measure mental problems (i.e., anxiety, insomnia, and depressive symptoms), and help-seeking behavior and treatment for these mental problems.
Frontline medical workers had higher rates of any mental problem (52.6% vs. 34.0%, adjusted OR=1.88, 95% CI=1.57–2.25), anxiety symptoms (15.7% vs. 7.4%, adjusted OR=1.95, 95% CI=1.46–2.61), depressed mood (marginally insignificant; 14.3% vs. 10.1%, adjusted OR=1.32, 95% CI=0.99–1.76) and insomnia (47.8% vs. 29.1%, adjusted OR=1.96, 95% CI=1.63–2.36) than non-frontline medical workers. No significant difference was observed in terms of suicidal ideation (12.0% vs. 9.0%, adjusted OR=1.25, 95% CI=0.92–1.71), help-seeking (4.5% vs. 4.5%, adjusted OR=1.00, 95% CI=0.53–1.87) or treatment (3.4% vs. 2.3%, adjusted OR=1.38, 95% CI=0.54–3.52) for mental problems.
The case-control nature of the data precludes causal inferences, and there is a possibility of bias related to self-reports.
Frontline medical workers had more mental problems but comparable help-seeking behaviors and treatment for these problems than non-frontline medical workers. These findings highlight the timely mental support and intervention for medical workers, especially for those on the frontline.
Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue‐specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone ...H3‐Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3‐Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two‐step mechanism for UTX‐mediated demethylation at muscle‐specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Interestingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene.
Copper is a vital mineral, and an optimal amount of copper is required to support normal physiologic processes in various systems, including the cardiovascular system. Over the past few decades, ...copper-induced cell death, named cuproptosis, has become increasingly recognized as an important process mediating the pathogenesis and progression of cardiovascular disease (CVD), including atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. Therefore, an in-depth understanding of the regulatory mechanisms of cuproptosis in CVD may be useful for improving CVD management. Here, we review the relationship between copper homeostasis and cuproptosis-related pathways in CVD, as well as therapeutic strategies addressing copper-induced cell death in CVD.
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