Abstract
The changes of broad emission lines should be a crucial issue in understanding the physical properties of changing-look active galactic nuclei (CL-AGNs). Here we present the results of an ...intensive and homogeneous 6 month long reverberation mapping (RM) monitoring campaign during a low-activity state of the CL-AGN Seyfert galaxy NGC 3516. Photometric and spectroscopic monitoring was carried out during 2018–2019 with the Lijiang 2.4 m telescope. The sampling is 2 days in most nights, and the average sampling is ∼3 days. The rest-frame time lags of H
α
and H
β
are
and
days, respectively. From an rms H
β
line dispersion of
σ
line
= 1713.3 ± 46.7 km s
−1
and a virial factor of
f
σ
= 5.5, the central black hole mass of NGC 3516 is estimated to be
, which is in agreement with previous estimates. The velocity-resolved delays show that the time lags increase toward negative velocity for both H
α
and H
β
. The velocity-resolved RM of H
α
is done for the first time. These RM results are consistent with other observations before the spectral-type change, indicating a basically constant broad-line region structure during the CL process. The CL model of changes of accretion rate seems to be favored by long-term H
β
variability and RM observations of NGC 3516.
Abstract Under the hypothesis of gravitational redshift induced by the central supermassive black hole and based on line widths and shifts of redward-shifted H β and H α broad emission lines for more ...than 8000 Sloan Digital Sky Survey DR7 active galactic nuclei (AGNs), we measure the virial factor in determining supermassive black hole masses. The virial factor had been believed to be independent of accretion radiation pressure on gas clouds in broad-line regions (BLRs) and only dependent on the inclination effects of BLRs. The virial factor measured spans a very large range. For the vast majority of AGNs (>96%) in our samples, the virial factor is larger than the f = 1 usually used in the literature. The f -correction makes the percent of high-accreting AGNs decrease by about 100 times. There are positive correlations of f with the dimensionless accretion rate and Eddington ratio. The redward shifts of H β and H α are mainly of gravitational origin, confirmed by a negative correlation between the redward shift and the dimensionless radius of the BLR. Our results show that radiation pressure force is a significant contributor to the measured virial factor, containing the inclination effects of the BLR. The usually used values of f should be corrected for high-accreting AGNs, especially high-redshift quasars. The f -correction increases their masses by 1–2 orders of magnitude, which will make it more challenging to explain the formation and growth of supermassive black holes at high redshifts.
Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is ...significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5'monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ginsenoside-Rg1 (G-Rg1) is an agent isolated from Panax ginseng that exerts anti-fibrotic effects; however, the mechanism is still unclear. Herein, we investigated whether G-Rg1 administration can ...mitigate or reverse unilateral ureteral obstruction (UUO)-induced renal fibrosis by regulating the Klotho/transforming growth factor (TGF)-β1/Smad signaling pathway in rats. Sprague–Dawley male rats were subjected to UUO, and rats in the treatment group were administered G-Rg1 or G-Rg1 plus Klotho short hairpin RNA interference (shRNA), while rats in the control and model groups were administered vehicle for 14 d. Epithelial–mesenchymal transition (EMT) biomarkers and Klotho/TGF-β1 signaling molecules were examined by immunohistochemistry, quantitative real-time PCR and Western blotting. Immunohistochemistry showed that UUO induced increased pro-fibrotic TGF-β1 expression, overexpression of the mesenchymal marker, α-smooth muscle actin (α-SMA), and suppression of the epithelial marker, E-cadherin. Moreover, Western blotting analysis indicated that UUO promoted TGF-β1 and phosphorylated Smad3 (p-Smad3) expression (p<0.01), but blocked Klotho and Smad7 expression (p<0.01). After G-Rg1 administration, the UUO-induced TGF-β1 and p-Smad3 expression was suppressed (p<0.01), whereas the reduced Klotho and Smad7 expression was reversed (p<0.05), followed by amelioration of the EMT process. Intriguingly, the G-Rg1 effects were largely abrogated by Klotho knockdown. Furthermore, Klotho expression was upregulated by G-Rg1 treatment at the mRNA and protein levels. Our results suggest that G-Rg1 may be beneficial for ameliorating renal fibrosis by targeting Klotho/TGF-β1/Smad signaling in UUO rats.
RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D ...structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30-692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
We report on the results of a new spectroscopic monitoring campaign of the quasar PG 0026+129 at the Calar Alto Observatory 2.2 m telescope from 2017 July to 2020 February. Significant ...variations in the fluxes of the continuum and broad emission lines, including H
β
and He
ii
, were observed in the first and third years, and clear time lags between them are measured. The broad H
β
line profile consists of two Gaussian components: an intermediate-width H
with an FWHM of 1964 ± 18
and another very broad H
with an FWHM of 7570 ± 83
. H
has long time lags of ∼40–60 days in the rest frame, while H
shows nearly zero time delay with respect to the optical continuum at 5100 Å. The velocity-resolved delays show consistent results: lags of ∼30–50 days at the core of the broad H
β
line and roughly zero lags at the wings. H
has a redshift of ∼400
, which seems to be stable for nearly 30 yr by comparing with archived spectra, and may originate from an infall. The rms spectrum of H
shows a double-peaked profile with brighter blue peak and extended red wing in the first year, which matches the signature of a thin disk. Both the double-peaked profile and the near-zero lag suggest that H
comes from a region associated with the part of the accretion disk that emits the optical continuum. Adopting the FWHM (in the rms spectrum) and the time lag measured for the total H
β
line, and a virial factor of 1.5, we obtain a virial mass of
for the central black hole in this quasar.
Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it ...into biological signals, and thereby promote alveolar bone remodelling, is unclear.
Materials and Methods
An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting.
Results
Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling.
Conclusions
Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.
Mechanical force in vivo induced periodontal ligament stem cell proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation. The activation of TRPV4 in PDLSCs under mechanical force contributes to the changes in their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation, and immunoregulation and modulates bone remodelling during tooth movement.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
We performed a rigorous reverberation-mapping analysis of the broad-line region (BLR) in a highly accreting (
L
/
L
Edd
= 0.74–3.4) active galactic nucleus, Markarian 142 (Mrk 142), for the ...first time using concurrent observations of the inner accretion disk and the BLR to determine a time lag for the H
β
λ
4861 emission relative to the ultraviolet (UV) continuum variations. We used continuum data taken with the Niel Gehrels Swift Observatory in the
UVW
2 band, and the Las Cumbres Observatory, Dan Zowada Memorial Observatory, and Liverpool Telescope in the
g
band, as part of the broader Mrk 142 multiwavelength monitoring campaign in 2019. We obtained new spectroscopic observations covering the H
β
broad emission line in the optical from the Gemini North Telescope and the Lijiang 2.4 m Telescope for a total of 102 epochs (over a period of 8 months) contemporaneous to the continuum data. Our primary result states a UV-to-H
β
time lag of
8.68
−
0.72
+
0.75
days in Mrk 142 obtained from light-curve analysis with a Python-based running optimal average algorithm. We placed our new measurements for Mrk 142 on the optical and UV radius–luminosity relations for NGC 5548 to understand the nature of the continuum driver. The positions of Mrk 142 on the scaling relations suggest that UV is closer to the “true” driving continuum than the optical. Furthermore, we obtain
log
(
M
•
/
M
⊙
)
= 6.32 ± 0.29 assuming UV as the primary driving continuum.
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