170 research outputs found
Dynamics of Vesicle Formation from Lipid Droplet: Mechanism and Controllability
A coarse-grained model developed by Marrink et al. [J. Phys. Chem. B 111,
7812 (2007)] is applied to investigate vesiculation of lipid
[dipalmitoylphosphatidylcholine (DPPC)] droplets in water. Three kinds of
morphologies of micelles are found with increasing lipid droplet size. When the
initial lipid droplet is smaller, the equilibrium structure of the droplet is a
spherical micelle. When the initial lipid droplet is larger, the lipid ball
starts to transform into a disk micelle or vesicle. The mechanism of vesicle
formation from a lipid ball is analyzed from the self-assembly of DPPC on the
molecular level, and the morphological transition from disk to vesicle with
increasing droplet size is demonstrated. Importantly, we discover that the
transition point is not very sharp, and for a fixed-size lipid ball, the disk
and vesicle appear with certain probabilities. The splitting phenomenon, i.e.,
the formation of a disk/vesicle structure from a lipid droplet, is explained by
applying a hybrid model of the Helfrich membrane theory. The elastic module of
the DPPC bilayer and the smallest size of a lipid droplet for certain formation
of a vesicle are successfully predicted.Comment: 22 pages, 11 figures Submitted to J. Chem. Phy
Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury.
Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1 (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1α activity, leading to Foxp3 downregulation and RORγt and IL-17A upregulation in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow-derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1α and upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro. Silencing of HIF-1α in ATF3 KO mice ameliorated IRI-induced liver damage in parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1α signaling, which was crucial for the modulation of TLR4-driven inflammatory responses and T cell development. The present study provides potential therapeutic targets for the treatment of liver IRI followed by liver transplantation
Hepatitis B virus inhibition in mice by lentiviral vector mediated short hairpin RNA
<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. The major challenges for current therapies are the low efficacy of current drugs and the occurrence of drug resistant HBV mutations. RNA interference (RNAi) of virus-specific genes offers the possibility of developing a new anti-HBV therapy. Recent reports have shown that lentiviral vectors based on HIV-1 are promising gene delivery vehicles due to their ability to integrate transgenes into non-dividing cells. Herein, a lentivirus-based RNAi system was developed to drive expression and delivery of HBV-specific short hairpin RNA (shRNA) in a mouse model for HBV replication.</p> <p>Methods</p> <p>Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the sera of the mice were analyzed by quantitative sandwich enzyme linked immunosorbent assay (ELISA) technique, hepatitis B core antigen (HBcAg) and HBsAg in the livers of the mice were detected by immunohistochemical assay, HBV DNA and HBV mRNA were measured by fluorogenic quantitative polymerase chain reaction (FQ-PCR) and quantitative real-time PCR respectively.</p> <p>Results</p> <p>Co-injection of HBV plasmids together with the lentivirus targeting HBV shRNA induced an RNAi response. Secreted HBsAg was reduced by 89% in mouse serum, and HBeAg was also significantly inhibited, immunohistochemical detection of HBcAg or HBsAg in the liver tissues also revealed substantial reduction. Lentiviral mediated shRNA caused a significant suppression in the levels of viral mRNA and DNA synthesis compared to the control group.</p> <p>Conclusion</p> <p>Lentivirus-based RNAi can be used to suppress HBV replication in vivo, it might become a potential therapeutic strategy for treating HBV and other viral infections.</p
Phase transition of a single star polymer: a Wang-Landau sampling study
Star polymer is a typical nonlinear macromolecule possessing special
thermodynamic behaviors for the existence of a jointing point. The
thermodynamic transitions of a single star polymer are systematically studied
with bond fluctuation model using Wang-Landau sampling technique. A new
analysis method applying the shape factor is proposed to determine coil-globule
(CG) and liquid-crystal (LC) transitions, which shows higher efficiency and
precision than canonical specific heat function. It is found that the LC
transition of star polymer at lower temperature obeys the identical scaling law
as linear polymer. With the increase of the arm density of star polymer,
however, the CG transition point, corresponding to {\theta} temperature, shifts
towards the LC transition and the reason comes from the high density arms of
star polymer, which requires the lower temperature for attracting force to
overcome the volume excluding effects of chain. This work clearly demonstrates
that the distinction of linear and star polymers in structures only affects CG
transition and has no influence on LC transition.Comment: 30 pages, 10 figures, submit to JC
Visualizing delocalized correlated electronic states in twisted double bilayer graphene
The discovery of interaction-driven insulating and superconducting phases in
moir\'e van der Waals heterostructures has sparked considerable interest in
understanding the novel correlated physics of these systems. While a
significant number of studies have focused on twisted bilayer graphene,
correlated insulating states and a superconductivity-like transition up to 12 K
have been reported in recent transport measurements of twisted double bilayer
graphene. Here we present a scanning tunneling microscopy and spectroscopy
study of gate-tunable twisted double bilayer graphene devices. We observe
splitting of the van Hove singularity peak by ~20 meV at half-filling of the
conduction flat band, with a corresponding reduction of the local density of
states at the Fermi level. By mapping the tunneling differential conductance we
show that this correlated system exhibits energetically split states that are
spatially delocalized throughout the different regions in the moir\'e unit
cell, inconsistent with order originating solely from onsite Coulomb repulsion
within strongly-localized orbitals. We have performed self-consistent
Hartree-Fock calculations that suggest exchange-driven spontaneous symmetry
breaking in the degenerate conduction flat band is the origin of the observed
correlated state. Our results provide new insight into the nature of
electron-electron interactions in twisted double bilayer graphene and related
moir\'e systems.Comment: 24 pages, 5 figure
Inhibition of MTA1 by ERα contributes to protection hepatocellular carcinoma from tumor proliferation and metastasis
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