Fibrotic remodelling contributes to heart failure in myocardial infarction. MicroRNAs (miRNAs) play a crucial role in myocardial fibrosis. However, current antifibrotic therapeutic strategies using ...miRNAs are far from effective. In this study, we aim to investigate the effect of miR-96-5p on cardiac fibrosis. Our work reveals a significant upregulation of miR-96-5p level in the ventricular tissues of myocardial infarction mice, as well as in neonatal rat cardiac fibroblasts stimulated with TGF-β or Ang II as shown by qPCR assay. In myocardial infarction mice,
knockdown using antagomir alleviates the aggravated cardiac fibrosis and exacerbated myocardial function caused by myocardial infarction surgery as shown by the echocardiography and Masson's staining analysis. In contrast, immunofluorescence staining results reveal that miR-96-5p overexpression in neonatal rat cardiac fibroblasts contributes to an increase in the expressions of fibrosis-associated genes and promotes the proliferation and differentiation of cardiac fibroblasts. Conversely, miR-96-5p downregulation using inhibitor presents adverse consequences. Furthermore, Smad7 expression is downregulated in fibrotic cardiac tissues, and the
gene is identified as a direct target of miR-96-5p by dual luciferase assay. Indeed,
knockdown weakens the anti-fibrotic effect of the miR-96-5p inhibitor on cardiac fibroblasts. Moreover, Smad3 phosphorylation is elevated in fibrotic cardiac tissues, and interestingly, the Smad3 inhibitor suppresses the profibrotic effect of the miR-96-5p mimic. Taken together, our findings demonstrate that the Smad7/Smad3 signaling pathway mediates the profibrotic effect of miR-96-5p in cardiac fibrosis.
Compared with airborne gravimetry, a technique frequently used to infer the seafloor topography at places inaccessible to ship soundings due to the presence of ice shelf or ice mélange, airborne ...gravity gradiometry inherently could achieve higher spatial resolution, thus it is promising for improved inference of seafloor topography. However, its estimation capability has not been demonstrated by real projects. Theoretical analysis through admittance shows that compared with gravity disturbance, gravity gradient is more sensitive to the short-wavelength seafloor topography but diminishes faster with the increase of the distance between the seafloor and airplane, indicating its superiority is recovering short-wavelength topographic features over shallow waters. We present the first numerical experiment that estimates seafloor topography from a 0.4-km resolution, real airborne gravity gradients. It is shown that airborne gravity gradiometry can recover smaller topographic features than typical airborne gravimetry, but the estimation accuracy is only ±17 m due to the presence of subsurface density variations. The long-wavelength effect of the subsurface density variations can be removed with the aid of constraining bathymetry inside the study area, whereas the short wavelengths cannot. This study expands the applications of airborne gravity gradiometry, and helps glaciologists understand its performance in seafloor topography estimation.
Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear.
We retrospectively recruited 68 pairs of samples of
(MTB) from ...recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection. The BACTEC MGIT was performed to compare differences in drug susceptibility profiles between two episodes.
62 (91.2%) out of 68 confirmed recurrence were due to relapse, whereas the remaining six (8.8%) were due to reinfection. And there was a strong association between earlier relapse and underlying chronic diseases. In addition, the MTB isolates from non-diabetic patients had a higher mutation rate than those from diabetic patients. A community transmission was also identified in our cohort. Levofloxacin resistance was the most frequently observed drug resistance for 12.9% relapse cases.
The relapse of a previous episode in Beijing. The underlying chronic diseases are associated with an earlier TB relapse. MTB isolates were more prone to develop levofloxacin resistance than moxifloxacin resistance after FQ exposure. The patients at high-risk for relapses deserve more careful investigation.
Gastric cancer with bone marrow metastasis and disseminated intravascular coagulation constitutes a highly aggressive gastric cancer subtype which presents a peculiar biological behavior and very ...poor prognosis. Retrospective studies have shown chemotherapy could prolong survival, but a prospective trial is still unavailable. This study is the first prospective clinical trial to evaluate the safety and efficacy of chemotherapy for advanced gastric cancer patients with bone marrow metastasis.
To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM).
A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health ...Study II.
The adjusted risk ratios for GDM across the age at menarche categories (≤11, 12, 13, and ≥14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI.
These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity.
In the hydraulically suspended passive shutdown assembly, in order to prevent the liquid suspension rod falling too fast and the outer tube from violent impact, it is necessary to study the way to ...increase flow resistance. This study added grooves to the wall of the narrow channel to increase its flow resistance. Using the RNG k-ε turbulence model in Fluent, the influence of the groove structure parameters and the Reynolds number on the flow resistance of the narrow channel was discussed to find the optimal groove structure parameters. The results showed that the flow resistance of the narrow channel increased with the increase in the concave–convex ratio, and when the concave–convex ratio was small, the flow resistance decreased with increased groove thickness, while when the concave–convex ratio exceeded a certain critical value, the flow resistance increased with increased groove thickness. Additionally, the growth rate slowed down when the concave–convex ratio was greater than 3:1. As the unit length decreased, the flow resistance first increased and then decreased. When the unit length was 6 mm, the flow resistance reached the maximum. With the increase in the Reynolds number, the intensity of the local high-turbulence kinetic energy clearly increased.
Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous ...genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear.
We constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. Based on our multi-omics integrative analysis, 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P < 0.05). The risk gene of ORMDL3 showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). The ORMDL3
cholangiocytes have prominently higher metabolism activity score than ORMDL3
cholangiocytes (P = 1.38 × 10
). Compared with ORMDL3
cholangiocytes, there were 77 significantly differentially expressed genes among ORMDL3
cholangiocytes (FDR < 0.05), and these significant genes were associated with autoimmune diseases-related functional terms or pathways. The ORMDL3
cholangiocytes exhibited relatively high communications with macrophage and monocyte. Compared with ORMDL3
cholangiocytes, the VEGF signaling pathway is specific for ORMDL3
cholangiocytes to interact with other cell populations.
To the best of our knowledge, this is the first study to integrate genetic information with single cell sequencing data for parsing genetics-influenced liver cells for PBC risk. We identified that ORMDL3
cholangiocytes with higher metabolism activity play important immune-modulatory roles in the etiology of PBC.
Older adults with type 2 diabetes are at higher risk of developing common geriatric syndromes and have a lower quality of life. To prevent type 2 diabetes in older adults, it's unclear whether the ...health benefits of physical activity (PA) will be influenced by the harms caused by increased exposure to air pollution during PA, especially in developing countries with severe air pollution problem. We aimed to investigate the joint effects of PA and long-term exposure to air pollution on the type 2 diabetes in older adults from China.
This cross-sectional study was based on the China Multi-Ethnic cohort (CMEC) study. The metabolic equivalent of PA was calculated according to the PA scale during the CMEC baseline survey. High resolution air pollution datasets (PM
, PM
and PM
) were collected from open products. The joint effects were assessed by the marginal structural mean model with generalized propensity score.
A total of 36,562 participants aged 50 to 79 years were included in the study. The prevalence of type 2 diabetes was 10.88%. The mean (SD) level of PA was 24.93 (18.60) MET-h/d, and the mean (SD) level of PM
, PM
, and PM
were 70.00 (23.32) µg/m
, 40.45 (15.66) µg/m
and 27.62 (6.51) µg/m
, respectively. With PM
< 92 µg/m
, PM
< 61 µg/m
, and PM
< 36 µg/m
, the benefit effects of PA on type 2 diabetes was significantly greater than the harms due to PMs when PA levels were roughly below 80 MET-h/d. With PM
≥ 92 µg/m
, PM
≥ 61 µg/m
, and PM
≥ 36 µg/m
, the odds ratio (OR) first decreased and then rose rapidly with confidence intervals progressively greater than 1 and break-even points close to or even below 40 MET-h/d.
Our findings implied that for the prevention of type 2 diabetes in older adults, the PA health benefits outweighed the harms of air pollution except in extreme air pollution situations, and suggested that when the air quality of residence is severe, the PA levels should ideally not exceed 40 MET-h/d.
It is well-known that high-frequency information (e.g. textures, edges) is significant for single image super-resolution (SISR). However, Existing of deep Convolutional Neural Network (CNN) based ...methods directly model mapping function from low resolution (LR) to high resolution (HR), and they treat high-frequency and low-frequency information equally during feature extraction. Therefore, the high-frequency learning mode can not be sufficiently attentive, resulting in inaccurate representation of some local details. In this study, we aim to build potential frequencies' relations and handle high-frequency and low-frequency information differentially. Specifically, we propose a novel Frequency Separation Network (FSN) for image super-resolution (SR). In FSN, a new Octave Convolution (OC) is adopted, which uses four operations to perform information update and frequency communication between high frequency and low frequency features. In addition, global and hierarchical feature fusion are employeed to learn elaborate and comprehensive feature representations, in order to further benefit the quality of final image reconstruction. Extensive experiments conducted on benchmark datasets demonstrate the state-of-the-art performance of our method.
PDF
