Search

Background Numerous studies were demonstrated the inverse relationship between all kinds of physical activity (PA) and cardiovascular diseases (CVDs), few of them focus on the new-onset hypertension. Therefore, this study was aimed to determine the impact of long-term PA on the risk of new-onset hypertension in type 2 diabetes mellitus (T2DM) patients with pre-hypertension.Methods A total of 268 T2DM patients with pre-hypertension were recruited between January and December 2015, and followed them up until December 2020. All patients were took PA self-assessment. Demographic, clinical, laboratory, radiologic, treatments, complications, lifestyle and clinical outcomes data were extracted from electronic medical records or collected through a structured interview.Results During 5 year follow-up, the incidence of new-onset hypertension was significantly lower in PA group (15.5% vs 35.4%, p1C) (OR 1.206, 95%CI 1.006 to 1.446, pConclusion These results suggested that long-term PA might be an important protective factor for new-onset hypertension in overweight and poor blood glycaemic controlled pre-hypertensive T2DM patients.

Neutrophils, an important component of the innate immune system, release extracellular traps (NETs) to eliminate invading pathogens by trapping and killing microbes. Recent studies have shown that NETs play a multitude of additional roles in immunity and inflammatory diseases. Therefore, NETs may be involved in persistent hepatitis B virus (HBV) infection, and the objectives of the current study were to determine whether HBV influences NET release and to identify the underlying mechanisms. HBV-infected mice (C57BL/6) were used to detect the efficiency of bacterial eradication by neutrophils in vivo. Primary neutrophils and circulating blood samples were collected from 40 patients with chronic hepatitis B infection, as well as 40 healthy controls, to detect NET release using a Quant-iT Pico Green dsDNA assay, Western blotting, and live-cell imaging and to determine the levels of HBV-DNA and HBV markers. NET release was decreased in patients with chronic hepatitis B infection, and hepatitis B surface Ag, hepatitis B E Ag, and hepatitis B core Ab levels negatively correlated with NET release. We also examined the effect of HBV proteins (HBV X protein, HBV C protein, HBV E protein, and HBV S protein) on NET release in vitro. Based on flow cytometry, cytochrome c reduction assay, and Western blotting, HBV C protein and HBV E protein inhibited NET release by decreasing reactive oxygen species production and autophagy. Overall, HBV may inhibit NET release by modulating reactive oxygen species production and autophagy to escape the immune system and promote the establishment of chronic infection.

ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) provides an efficient way to analyze nucleosome-free regions and has been applied widely to identify transcription factor footprints. Both applications rely on the accurate quantification of insertion events of the hyperactive transposase Tn5. However, due to the presence of the PCR amplification, it is impossible to accurately distinguish independently generated identical Tn5 insertion events from PCR duplicates using the standard ATAC-seq technique. Removing PCR duplicates based on mapping coordinates introduces increasing bias towards highly accessible chromatin regions. To overcome this limitation, we establish a UMI-ATAC-seq technique by incorporating unique molecular identifiers (UMIs) into standard ATAC-seq procedures. UMI-ATAC-seq can rescue about 20% of reads that are mistaken as PCR duplicates in standard ATAC-seq in our study. We demonstrate that UMI-ATAC-seq could more accurately quantify chromatin accessibility and significantly improve the sensitivity of identifying transcription factor footprints. An analytic pipeline is developed to facilitate the application of UMI-ATAC-seq, and it is available at https://github.com/tzhu-bio/UMI-ATAC-seq., Tao Zhu et al. present UMI-ATAC-seq, an improved ATAC-seq technique that uses unique molecular identifiers to avoid filtering out true independent - but identical - Tn5 insertion events that would otherwise be treated as PCR duplicates. They apply UMI-ATAC-seq to rice panicle samples and show that their approach improves the quantification of chromatin accessibility and footprinting.

Background. The coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This coronavirus disease has spread globally as a pandemic. Quantitative reverse transcription PCR (qRT-PCR) is established as a diagnostic assay to detect SARS-CoV-2 in patient specimens. The increasing numbers of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great challenges for the test laboratories.Methods. The test specimens were collected by the hospitals or CDC in Hubei province. Viral RNA is extracted by manual column extraction and automated magnetic bead extraction method by MGISP-960 automated sample preparation system. qRT-PCR for the novel coronavirus is used in this process and several approaches were applied to prevent contamination and monitor process quality.Results. We introduced a high-throughput nucleic acid detection mode, Huo-Yan Laboratory, which has an automated process and rigorous quality control measures to ensure the stability and reliability of detection in large-scale specimens. The automated extraction method based on MGISP-960 sample preparation system has comparable results of manual extraction, and requires less time and personnel. The quality control monitoring results suggests that the quality control approaches in testing large-scale specimens are effective, and the test results are stable and reliable. Huo-Yan Laboratory mode can be flexibly adapted to the requirement of different throughput which is contributed to epidemic control in various places.

BACKGROUND Ischemia-reperfusion injury is associated with vascular dysfunction. The aim of this study was to investigate the role of emodin, a Chinese herbal medicine, in hypoxia-reoxygenation injury in cultured human aortic endothelial cells (HAECs) and its effects on the expression of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and endothelial nitric oxide synthase (eNOS) signaling pathway. MATERIAL AND METHODS An in vitro hypoxia-reoxygenation model used cultured human aortic endothelial cells (HAECs). A colorimetric method evaluated the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ). Phosphorylation of PPAR-γ and endothelial nitric oxide synthase (eNOS) were measured by Western blotting. Expression of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Nitric oxide (NO) production was detected by diaminofluorescein-FM diacetate (DAF-FM DA) fluorescence. Immunoprecipitation was used to evaluate the molecular coupling of heat shock protein (HSP)90 and eNOS. RESULTS Hypoxia-reoxygenation injury of HAECs reduced the activity and phosphorylation of PPAR-γ, and eNOS, NO production, and HSP90/eNOS molecular coupling in a time-dependent manner. Hypoxia-reoxygenation increased the levels of inflammatory cytokines TNF-α, IL-6, and IL-8 in a time-dependent manner. Emodin treatment recovered PPAR-γ activity and phosphorylation, eNOS phosphorylation, and HSP90/eNOS coupling in HAECS in a concentration-dependent manner, which was reversed by the PPAR-γ inhibitor GW9662, and the eNOS inhibitor, L-NAME. The recovery of HSP90/eNOS coupling by emodin was impaired by GW9662 treatment. CONCLUSIONS An in vitro hypoxia-reoxygenation (ischemia-reperfusion injury) model of induction of endothelial cell inflammatory mediators showed that emodin recovered the PPAR-γ and eNOS pathway activity.

BACKGROUND This study was aimed to investigate the protective role of baicalin on vascular endothelium exposed to ischemia reperfusion injury and the involved molecular mechanisms. MATERIAL AND METHODS Cultured human arterial endothelial cells (HAECs) were exposed to hypoxia/deoxygenation (H/R). Cells were also treated with baicalin at serially diluted concentrations. Cells were also treated with PKC activator PEP005 or specific siRNA against protein kinase Cδ (PKCδ). MTT assay was used to evaluate the cell viabilities. Flow cytometry was used to detect cell apoptosis. The protein phosphorylation and expression levels were determined by Western blotting. RESULTS PKCδ-siRNA transfection increased cell viabilities and reduced cell apoptosis in HAECs exposed to H/R. Baicalin treatment preserved cell viabilities and reduced apoptosis of H/R-exposed HAECs in a concentration- dependent manner. Baicalin treatment reduced phosphorylation levels of PKCδ and p53, as well as the expression levels of active caspase3 and bax in HAECs exposed to H/R. The treatment of PKC activator PEP005 impaired the protective effects of baicalin in increasing cell viabilities and reducing apoptosis in HAECs exposed to H/R. CONCLUSIONS Baicalin exerts vascular a protective effect on HAECs exposed to H/R by reducing cell apoptosis. The PKCδ/p53 apoptotic signaling pathway was the pharmacological target of baicalin.

Additional file 1: Figure S1. The correlation of each metric with yield (ReadsM). The linear regression line is shown in blue.

Background Exercise training is beneficial for cardiac rehabilitation. Nevertheless, few study focused on the role of high-intensity interval training (HIIT) in cardiac repair. The current study aimed to elucidate the effect of HIIT on cardiac rehabilitation and the involved mechanisms after acute myocardial infarction (MI). Methods A total of 65 male rats underwent coronary ligation or sham operation and were randomly assigned to 4 groups: sham (n = 10), sedentary (MI-Sed, n = 12), moderate-intensity continuous training (MI-MCT, n = 12) and HIIT (MI-HIIT, n = 12). One week after MI induction, adaptive training starts follow by formal training. After the experiment, cardiac functions were determined by echocardiography and hemodynamic measurements. Changes in infarct size, collagen accumulation, myofibroblasts, angiogenesis, inflammation level, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system (RAAS) activities were measured. Data were analyzed by one-way ANOVA. Results After MI, cardiac structure and function were significantly deteriorated. However, post-MI HIIT for 8 weeks had significantly ameliorated left ventricular end-diastolic pressure (LVEDP), LV systolic pressure (LVSP), and maximum peak velocities of relaxation (–dP/dtmax). Moreover, it preserved cardiac functions, reduced infarct size, protected the myocardium structure, increased angiogenesis and decreased the myofibroblasts and collagen accumulation. HIIT for 4 weeks had no effect on LVEDP, –dP/dtmax, infarct size and angiogenesis. Additionally, it induced inflammation response and repressed ET-1 and RAAS activities were found in myocardium and peripheral circulation after HIIT. Conclusion Our results suggested that post-MI HIIT had a positive role in cardiac repair, which might be linked with the induction of inflammation and inhibition of ET-1 and RAAS activities.

Neutrophils, an important component of the innate immune system, release extracellular traps (NETs) to eliminate invaded pathogens by trapping and killing microbes. A dysfunctional innate immune response is a major cause of persistent hepatitis B virus (HBV) infection. HBV has been shown to reduce neutrophil responses. The objectives of the present study were to determine whether HBV influenced NETs release and to identify the underlying mechanisms. Primary neutrophils and circulating blood samples were collected from 40 patients with a chronic hepatitis B infection (CHB) and 40 healthy controls to detect NETs release using a Quant-iT Pico Green dsDNA assay and to determine the levels of HBV-DNA and HBV markers. NETs release was decreased in patients with a CHB infection, and hepatitis B surface antigen, hepatitis B e antigen and hepatitis B core antibody levels negatively correlated with NETs release. The Quant-iT Pico Green dsDNA assay and western blotting were used to examine the effect of HBV proteins (HBV X protein, HBV C protein, HBV E protein and HBV S protein) on NETs releasein vitro. Based on the flow cytometry and western blot data, HBV C protein and HBV E protein inhibited NETs release by decreasing reactive oxygen species (ROS) production and autophagy. Overall, HBV may inhibit NETs release by modulating ROS production and autophagy to escape the immune system and promote the establishment of a chronic infection.

Endometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non‐coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non‐coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc‐NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. The role and function of Lnc‐NA in EEC remain unknown. In this study, we used quantitative real‐time polymerase chain reactions to confirm that Lnc‐NA expression was down‐regulated in 30 EEC cases (90%) and in EEC cell lines compared with that in the paired adjacent tissues and normal endometrial cells. In vitro experiments further demonstrated that overexpressing Lnc‐NA decreased EEC cell proliferation, migration and invasion and promoted apoptosis via inactivation of the apoptosis signalling pathway. Moreover, the results show that Lnc‐NA expression was positively correlated with NR4A1. Furthermore, Lnc‐NA regulated NR4A1 expression and activated the apoptosis signalling pathway to inhibit tumour progression. In summary, our results demonstrate that the Lnc‐NA‐NR4A1 axis could be a useful tumour suppressor and a promising therapeutic target for EEC.

FK506-binding protein 51 (FKBP51) is a member of the immunophilin family, with relevant roles in multiple signaling pathways, tumorigenesis and chemoresistance. However, the function of FKBP51 in papillary thyroid carcinoma (PTC) remains largely unknown. In the present study, increased FKBP51 expression was detected in PTC tissues as compared with adjacent normal tissues, and the expression level was associated with clinical tumor, node and metastasis stage. Using FKBP51-overexpressing K1 cells and FKBP51-knockdown TPC-1 cells, both human PTC cell lines, it was identified that FKBP51 promoted the migration and invasion of PTC, without affecting cell proliferation. Further investigation revealed that FKBP51 activated the NF-κB pathway and epithelial-to-mesenchymal transition (EMT) genes, and EMT was suppressed when NF-κB was inhibited. It was also assessed whether FKBP51 promoted the formation of cytoskeleton to promote migration and invasion of PTC using a tubulin tracker; however, no evidence of such an effect was observed. These results suggested that FKBP51 promotes migration and invasion through NF-κB-dependent EMT.

The charging time and the electrode gap distance are very important ignition parameters for the spark ignition process. The effects of these two parameters on the spark characteristics and the flame propagation of premixed methane–air mixtures were investigated experimentally at a constant pressure and a constant temperature by using a constant-volume bomb and a high-speed schlieren system. The parameters of the spark characteristics, including the spark voltage, the spark current, the spark duration and the lean burn ignition limit, were experimentally measured, and the spark resistance and the ignition energy were calculated on the basis of these parameters. By comparing the schlieren photographs of laminar flame propagation in different conditions taken by the high-speed schlieren devices, the effects of the ignition parameters on the cross-sectional area of the flame, the flame radius and the speed of flame propagation were analysed. The results show that the charging time and the electrode gap distance have important influences on the early kernel formation. Increasing the charging time or the electrode gap distance can significantly increase the influences of the effective radius of ignition and the original kernel size, can increase the ignition energy and can promote kernel development and flame propagation. Increasing the charging time or the electrode gap distance can effectively increase the lean burn ignition limit but, when the electrode gap distance increases to a certain extent, only increasing the charging time can increase the lean burn ignition limit further.

A portfolio optimization problem involves optimal allocation of finite capital to a series of assets to achieve an acceptable trade-off between profit and risk in a given investment period. In the paper, the extended Markowitz’s mean-variance portfolio optimization model is studied. A major challenge with this model is that it contains both discrete and continuous decision variables, which represent the assignment and allocation of assets respectively. To deal with this hard problem, this paper proposes an evolutionary algorithm with a new coding scheme that converts discrete variables into continuous ones. By this way, the mixed variables can be handled, and some of the constraints are naturally satisfied. The new approach is empirically studied and the experiment results indicate its efficiency.