miR-2954 Inhibits PI3K Signaling and Induces Autophagy and Apoptosis in Myocardium Selenium Deficiency

Background/Aims: Selenium (Se) deficiency can lead to several cardiac diseases, including Keshan disease in humans, mulberry heart disease in pigs and cardiac injury in chickens. MicroRNAs have been a research focus in recent years and have been shown to participate in a new avenue of cell death-autophagy, which can play a significant role in several types of heart disease. Methods: MicroRNAome analysis showed that the expression of miR-2954 was increased in the myocardium of selenium-deficient chickens, and PI3K was predicted to be the target gene. The target relationship between miR-2954 and PI3K was verified with a double fluorescence enzyme assay and RNA Protein Interaction Prediction and molecular docking software. qRT-PCR and western blotting were used to detect the expression of PI3K and related pathway components in selenium-deficient chickens and miR-2954 knockout/overexpression cardiomyocytes. Results: In this study, we observed that miR-2954 overexpression led to inhibition of PI3K pathway in vivo and in vitroled to inhibition of the PI3K pathway in vivo and in vitro. Conclusion: The expression of miR-2954 was increased in selenium-deficient myocardium, whereas overexpression of miR-2954 led to autophagy and apoptosis of myocardial cells during cardiac injury through regulation of the PI3K pathway; whether this phenomenon is a self-protection mechanism of the organism or damage caused by miR-2954 requires further study. Our findings provides new insight apoptosis in cardiomyocytes; additionally, we aim to provide a new direction for the diagnosis and targeted treatment of myocardial diseases

Fried food consumption and the risk of pancreatic cancer: A large prospective multicenter study

Background and aimsWhether fried food consumption is associated with the risk of pancreatic cancer remains elusive. We aimed to examine this association in a US population.MethodsA population-based cohort of 101,729 US adults was identified. Fried food consumption was assessed with a validated food frequency questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Explanatory analyses were conducted to identify main contributor(s) to the observed association.ResultsDuring an average follow-up of 8.86 years (900871.2 person-years), 402 pancreatic cancer cases occurred. High consumption of total fried foods (deep-fried plus pan-fried foods; HRquartile4 vs. 1 0.71, 95% CI 0.51–0.99, Ptrend = 0.047) and deep-fried foods (HRquartile 4 vs. 1 0.64, 95% CI 0.47–0.88, Ptrend = 0.011), but not pan-fried foods (HRquartile 4 vs. 1 0.98, 95% CI 0.73–1.32; Ptrend = 0.815), was found to be associated with a reduced risk of pancreatic cancer in a non-linear dose–response manner, which was not modified by predefined stratification factors and persisted in sensitivity analyses. In explanatory analyses, only chip consumption was found to be inversely associated with the risk of pancreatic cancer; consistently, the initial significant associations between total fried food and deep-fried food consumption and the risk of pancreatic cancer changed to be non-significant after omitting or further adjusting for chip consumption.ConclusionConsumption of deep-fried foods, but not pan-fried foods, is inversely associated with the risk of pancreatic cancer in this US population. The role of deep-fried foods in reducing the risk of pancreatic cancer appears to be mainly attributable to chips. More studies are needed to confirm our findings in other populations and settings

An autophagy-related diagnostic biomarker for uterine fibroids: FOS

Uterine fibroids (UFs) are the most common benign gynecologic tumors in reproductive-aged women. The typical diagnostic strategies of UFs are transvaginal ultrasonography and pathological feature, while molecular biomarkers are considered conventional options in the assessment of the origin and development of UFs in recent years. Here, we extracted the differential expression genes (DEGs) and differential DNA methylation genes (DMGs) of UFs from the Gene Expression Omnibus (GEO) database, GSE64763, GSE120854, GSE45188, and GSE45187. 167 DEGs with aberrant DNA methylation were identified, and further Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed by the relevant R package. We next discerned 2 hub genes (FOS, and TNFSF10) with autophagy involvement by overlapping 167 DEGs and 232 autophagic regulators from Human Autophagy Database. FOS was identified as the most crucial gene through the Protein–Protein Interactions (PPI) network with the correlation of the immune scores. Moreover, the down-regulated expression of FOS in UFs tissue at both mRNA and protein levels was validated by RT-qPCR and immunohistochemistry respectively. The area under the ROC curve (AUC) of FOS was 0.856, with a sensitivity of 86.2% and a specificity of 73.9%. Overall, we explored the possible biomarker of UFs undergoing DNA—methylated autophagy and provided clinicians with a comprehensive assessment of UFs

Probing Primordial Gravitational Waves: Ali CMB Polarization Telescope

In this paper, we will give a general introduction to the project of Ali CMB Polarization Telescope (AliCPT), which is a Sino-US joint project led by the Institute of High Energy Physics (IHEP) and has involved many different institutes in China. It is the first ground-based Cosmic Microwave Background (CMB) polarization experiment in China and an integral part of China's Gravitational Waves Program. The main scientific goal of AliCPT project is to probe the primordial gravitational waves (PGWs) originated from the very early Universe. The AliCPT project includes two stages. The first stage referred to as AliCPT-1, is to build a telescope in the Ali region of Tibet with an altitude of 5,250 meters. Once completed, it will be the worldwide highest ground-based CMB observatory and open a new window for probing PGWs in northern hemisphere. AliCPT-1 telescope is designed to have about 7,000 TES detectors at 90GHz and 150GHz. The second stage is to have a more sensitive telescope (AliCPT-2) with the number of detectors more than 20,000. Our simulations show that AliCPT will improve the current constraint on the tensor-to-scalar ratio $r$ by one order of magnitude with 3 years' observation. Besides the PGWs, the AliCPT will also enable a precise measurement on the CMB rotation angle and provide a precise test on the CPT symmetry. We show 3 years' observation will improve the current limit by two order of magnitude.Comment: 11 pages, 7 figures, 2 table

Advance in Pancreatic Cancer Diagnosis and Therapy

Pancreatic carcinoma is the fourth leading cause of cancer death in the word wild. Although the advance in treatment this disease, the 5-years survival rate is still rather low. In the recent year, many new therapy and treatment avenues have been developed for pancreatic cancer. In this chapter, we mainly focus on the following aspect: 1) the treatment modality in pancreatic cancer, including chemotherapy, radiotherapy, and immunotherapy; 2) the mechanism of pancreatic cancer treatment resistance, especially in cancer stem cells and tumor microenvironment; 3) the diagnosis tools in pancreatic cancer, including serum markers, imaging methods and endoscopic ultrasonography. Novel molecular probes based on the nanotechnology in the diagnosis of pancreatic cancer are also discussed

A Multiple Step-like Spectrum of Primordial Perturbation

We show that if the inflaton effective potential has multiple discontinuous points in its first derivative, the spectrum of primordial perturbation will be multiple step-like. We give a general analysis by applying a simple model. In principle, as long as the height of step is low enough, the result of spectrum will be consistent with observations.Comment: minor changes and Refs. added, publish in PL

Suppression of renal cell carcinoma growth in vivo by forced expression of vascular endothelial growth inhibitor

Vascular endothelial growth inhibitor (VEGI) has been associated with tumor-related vasculature in certain malignancies. However, its implication in renal cell carcinoma (RCC), an angiogenesis-dependent tumor, remains unknown. In the present study, we investigated the role played by VEGI in RCC. The expression of VEGI was examined in human renal tissue and RCC cell lines using immunohistochemical staining and RT-PCR, respectively. The biological impact of modifying the expression of VEGI in RCC cells was evaluated using in vitro and in vivo models. We show that VEGI mRNA is expressed in a wide variety of human RCC cell lines, all of normal renal and most of RCC tissue specimens. VEGI protein expression was observed in normal renal tubular epithelial cells, but was decreased or absent in RCC specimens, particularly in tumors with high grade. Moreover, forced expression of VEGI led to an inhibition of vascular endothelial tube formation, decrease in the motility and adhesion of RCC cells in vitro. Interestingly, forced expression of VEGI had no bearing on growth, apoptosis and invasive capacity of RCC cells. However, tumor growth was reduced in xenograft models. Immunohistochemical staining showed that microvessel density decreased in VEGI forced expression xenograft tumor samples. Taken together, our findings showed that the expression of VEGI is decreased in RCC, particularly in tumors with higher grade. Together with its inhibitory effect on cellular motility, adhesion, vascular endothelial tube formation and tumor growth in vivo, this suggests that VEGI functions mainly through inhibition of angiogenesis and is a negative regulator of aggressiveness during the development and progression of RCC

Theory of free space coupling to high-Q whispering gallery modes

A theoretical study of free space coupling to high-Q whispering gallery modes both in circular and deformed microcavities are presented. In the case of a circular cavity, both analytical solutions and asymptotic formulas are derived. The coupling efficiencies at different coupling regimes for cylinder incoming wave are discussed, and the maximum efficiency is estimated for the practical Gaussian beam excitation. In the case of a deformed cavity, the coupling efficiency can be higher if the excitation beam can match the intrinsic emission well and the radiation loss can be tuned by adjusting the degree of deformation. Employing an abstract model of slightly deformed cavity, we found that the asymmetric and peak like line shapes instead of the Lorentz-shape dip are universal in transmission spectra due to multi-mode interference, and the coupling efficiency can not be estimated from the absolute depth of the dip. Our results provide guidelines for free space coupling in experiments, suggesting that the high-Q ARCs can be efficiently excited through free space which will stimulate further experiments and applications of WGMs based on free space coupling.Comment: 8 pages, 4 figure

Direct evidence for cosmic-ray-induced correlated errors in superconducting qubit array

Correlated errors can significantly impact the quantum error correction, which challenges the assumption that errors occur in different qubits independently in both space and time. Superconducting qubits have been found to suffer correlated errors across multiple qubits, which could be attributable to ionizing radiations and cosmic rays. Nevertheless, the direct evidence and a quantitative understanding of this relationship are currently lacking. In this work, we propose to continuously monitor multi-qubit simultaneous charge-parity jumps to detect correlated errors and find that occur more frequently than multi-qubit simultaneous bit flips. Then, we propose to position two cosmic-ray muon detectors directly beneath the sample box in a dilution refrigerator and successfully observe the correlated errors in a superconducting qubit array triggered by muons. By introducing a lead shielding layer on the refrigerator, we also reveal that the majority of other correlated errors are primarily induced by gamma rays. Furthermore, we find the superconducting film with a higher recombination rate of quasiparticles used in the qubits is helpful in reducing the duration of correlated errors. Our results provide experimental evidence of the impact of gamma rays and muons on superconducting quantum computation and offer practical insights into mitigation strategies for quantum error correction. In addition, we observe the average occurrence rate of muon-induced correlated errors in our processor is approximately 0.40 min$^{-1}$cm$^{-2}$, which is comparable to the muon event rate detected by the muon detector with 0.506 min$^{-1}$cm$^{-2}$. This demonstrates the potential applications of superconducting qubit arrays as low-energy threshold sensors in the field of high-energy physics.Comment: 7 pages and 5 figures for the main text, 20 pages and 20 figures for the supplementary material