Aim
Endothelial cell injury assumes a fundamental part in the pathogenesis of atherosclerosis, and endothelial cell autophagy has protective effects on the development of atherosclerosis, although ...the underlying molecular regulation mechanism is indistinct. This study aimed to investigate whether microRNA‐214‐3p (miR‐214‐3p) is involved in the endothelial cell autophagy regulation of atherosclerosis.
Methods
We utilized ApoE−/− mice provided with a high‐fat diet (HFD) as atherosclerosis model. We analysed the level of miR‐214‐3p and the levels of autophagy‐related protein 5 (ATG5) and autophagy‐related protein 12 (ATG12) in the purified CD31+ endothelial cells from mouse aorta. Bioinformatics analysis and a dual‐luciferase reporter assay were performed to confirm the binding target of miR‐214‐3p. In vitro study, human umbilical vein endothelial cells (HUVECs) were transfected with miR‐214‐3p mimics/inhibitor and stimulated with 100 μg/mL oxidized low‐density lipoprotein (ox‐LDL) for 12 hours to initiate a stress‐repairing autophagic process.
Results
In mouse models, we identified an inverse correlation between miR‐214‐3p, ATG5 and ATG12. We observed that in young HUVECs, ox‐LDL‐initiated autophagy was repressed by miR‐214‐3p overexpression, as evaluated by autophagic protein analysis, microtubule‐associated protein 1 light chain 3B‐II (LC3B‐II) immunofluorescence assay and transmission electron microscopy (TEM). Also, miR‐214‐3p promoted ox‐LDL accumulation in HUVECs and THP‐1 monocyte adhesion. Conversely, in old HUVECs, suppression of miR‐214‐3p preserved the ability to initiate a protective autophagy reaction to the ox‐LDL stimulation.
Conclusion
miR‐214‐3p regulates ox‐LDL‐initiated autophagy in HUVECs by directly targeting the 3′UTR of ATG5 and may have a suitable role in the pathogenesis of atherosclerosis.
We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the ...relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.
Mergers of neutron stars are known to be associated with short γ-ray bursts
. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density ...increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field
(that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts
. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst
. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown
. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf
. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref.
). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do
. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.
This study was conducted to investigate the effects of fructooligosaccharide (FOS) and Bacillus licheniformis (B. licheniformis) on growth performance, body composition, intestinal enzymes activities ...and gut histology of Megalobrama terminalis. Nine experimental diets were formulated to contain three FOS levels (0, 3 and 6 g kg⁻¹) and three B. licheniformis levels (0, 1 and 5 × 10⁷ CFU g⁻¹) following a 3 × 3 factorial design. Accordingly, diets were named as 0/0, 0/3, 0/6, 1/0, 1/3, 1/6, 5/0, 5/3 and 5/6 (B. licheniformis/FOS). At the end of the 8‐week feeding trial, weight gain (WG) and specific growth rate (SGR) of fish fed 6 g kg⁻¹ FOS were both significantly (P < 0.01 and P < 0.05) higher than that of the other groups in terms of dietary FOS levels. Besides, WG and SGR of fish fed 1 × 10⁷ CFU g⁻¹ B. licheniformis were significantly (P < 0.05) higher than that of the control group in terms of dietary B. licheniformis levels. In addition, a significant interaction (P < 0.05) between dietary FOS and B. licheniformis was observed in finial weight, WG, SGR as well as the survival rate with the highest values all observed in fish fed diet 1/3. Hepatosomatic index, carcass lipid content, lipase activities as well as microvilli length increased significantly (P < 0.05) from 0 to 1 × 10⁷ CFU g⁻¹, but no significant difference (P > 0.05) was observed in terms of dietary FOS levels. In addition, a significant (P < 0.05) interaction of FOS and B. licheniformis was observed in both protease and Na⁺, K⁺‐ATPase activities with the highest value obtained in fish fed diet 1/3. The results indicated that the dietary applications of dietary FOS and B. licheniformis alone or in combination can significantly improve the growth performance, survival rate, intestinal enzymes activities as well as microvilli length of triangular bream. In addition, there is a significant interaction between dietary FOS and B. licheniformis. The best combination for this species is 3 g kg⁻¹ FOS with 1 × 10⁷ CFU g⁻¹ B. licheniformis.
ABSTRACT We present X-ray source catalogs for the 7 Ms exposure of the Chandra Deep Field-South (CDF-S), which covers a total area of 484.2 arcmin2. Utilizing wavdetect for initial source detection ...and ACIS Extract for photometric extraction and significance assessment, we create a main source catalog containing 1008 sources that are detected in up to three X-ray bands: 0.5-7.0 keV, 0.5-2.0 keV, and 2-7 keV. A supplementary source catalog is also provided, including 47 lower-significance sources that have bright ( ) near-infrared counterparts. We identify multiwavelength counterparts for 992 (98.4%) of the main-catalog sources, and we collect redshifts for 986 of these sources, including 653 spectroscopic redshifts and 333 photometric redshifts. Based on the X-ray and multiwavelength properties, we identify 711 active galactic nuclei (AGNs) from the main-catalog sources. Compared to the previous 4 Ms CDF-S catalogs, 291 of the main-catalog sources are new detections. We have achieved unprecedented X-ray sensitivity with average flux limits over the central 1 arcmin2 region of 1.9 × 10−17, 6.4 × 10−18, and 2.7 × 10−17 erg cm−2 s−1 in the three X-ray bands, respectively. We provide cumulative number-count measurements observing, for the first time, that normal galaxies start to dominate the X-ray source population at the faintest 0.5-2.0 keV flux levels. The highest X-ray source density reaches 50,500 deg−2, and 47% 4% of these sources are AGNs ( 23,900 deg−2).
The study reported and analyzed the current state of wastewater treatment plants (WWTPs) in urban China from the perspective of treatment technologies, pollutant removals, operating load and effluent ...discharge standards. By the end of 2013, 3508 WWTPs have been built in 31 provinces and cities in China with a total treatment capacity of 1.48×108m3/d. The uneven population distribution between China's east and west regions has resulted in notably different economic development outcomes. The technologies mostly used in WWTPs are AAO and oxidation ditch, which account for over 50% of the existing WWTPs. According to statistics, the efficiencies of COD and NH3–N removal are good in 656 WWTPs in 70 cities. The overall average COD removal is over 88% with few regional differences. The average removal efficiency of NH3–N is up to 80%. Large differences exist between the operating loads applied in different WWTPs. The average operating loading rate is approximately 83%, and 52% of WWTPs operate at loadings of <80%, treating up to 40% of the wastewater generated. The implementation of discharge standards has been low. Approximately 28% of WWTPs that achieved the Grade I-A Discharge Standard of Pollutants for Municipal Wastewater Treatment Plant (GB 18918–2002) were constructed after 2010. The sludge treatment and recycling rates are only 25%, and approximately 15% of wastewater is inefficiently treated. Approximately 60% of WWTPs have capacities of 1×104m3/d–5×104m3/d. Relatively high energy consumption is required for small-scale processing, and the utilization rate of recycled wastewater is low. The challenges of WWTPs are discussed with the aim of developing rational criteria and appropriate technologies for water recycling. Suggestions regarding potential technical and administrative measures are provided.
Display omitted
•3508 wastewater treatment plants (WWTPs) were summarized.•Population distribution and economic development caused regional difference of WWTPs.•Pollutant removal, operating load, discharge standards in 7 regions were presented.•Suggestions regarding potential technical and administrative measures were provided.
Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities.
To address the impact of neuropsychiatric symptoms ...of patients in different stages of AD on their caregivers' burden.
This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center.
All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI.
The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively).
The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.
Rice paddy plantation is the dominant agricultural land use throughout Asia. Rice paddy fields have been identified as important sites for methylmercury (MeHg) production in the terrestrial ecosystem ...and a primary pathway of MeHg exposure to humans in mercury (Hg) mining areas. We compared the source and distribution of Hg species in different compartments of the rice paddy during a complete rice-growing season at two different typical Hg-contaminated mining sites in Guizhou province, China: an abandoned site with a high Hg concentration in soil but a low concentration in the atmosphere and a current-day artisanal site with a low concentration in soil but a high concentration in the atmosphere. Our results showed that the flux of new Hg to the ecosystem from irrigation and atmospheric deposition was insignificant relative to the pool of old Hg in soil; the dominant source of MeHg to paddy soil is in situ methylation of inorganic Hg (IHg). Elevated MeHg concentrations and the high proportion of Hg as MeHg in paddy water and the surface soil layer at the artisanal site demonstrated active Hg methylation at this site only. We propose that the in situ production of MeHg in paddy water and surface soil is dependent on elevated Hg in the atmosphere and the consequential deposition of new Hg into a low-pH anoxic geochemical system. The absence of depth-dependent variability in the MeHg concentration in soil cores collected from the abandoned Hg mining site, consistent with the low concentration of Hg in the atmosphere and high pH of the paddy water and irrigation water, suggested that net production of MeHg at this site was limited. We propose that the concentration of Hg in ambient air is an indicator for the risk of MeHg accumulation in paddy rice.
Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we ...perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis. ERG-negative tumor cells, compared to ERG-positive cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids harbor tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.
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