What Differs on the Enzymatic Acetylation Mechanisms for Arylamines and Arylhydrazines Substrates? A Theoretical Study

The acetylation mechanisms of several selected typical substrates from experiments, including arylamines and arylhydrazines, are investigated with the density functional theory in this paper. The results indicate that all the transition states are characterized by a four-membered ring structure, and hydralazine (HDZ) is the most potent substrate. The bioactivity for all the compounds is increased in a sequence of PABA ≈ 4-AS < 4-MA < 5-AS ≈ INH < HDZ. The conjunction effect and the delocalization of the lone pairs of N atom play a key role in the reaction. All the results are consistent with the experimental data

C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages

Background/Aims: Interleukin-1β (IL-1β) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPβ regulates the production of IL-1β are unclear. In this study, we aimed to explore the role of C/EBPβ in regulating IL-1β production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. Methods: RAW264.7 macrophages were treated with 0, 25, 50 or 100 μg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1β secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1β was tested by dual-luciferase reporter assay. Results: Ox-LDL increased IL-1β production, accompanied with increasing C/EBPβ and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPβ deficiency in macrophages blocked ox-LDL-induced increases in IL-1β expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1β production, but not C/EBPβ expression. Dual-luciferase reporter results showed that overexpression of C/EBPβ significantly enhanced binding activity of p65 to IL-1β promoter. In addition, C/EBP 1β deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1β, IL-6, p65 and caspase-1. Conclusions: Our results demonstrate that C/EBPβ acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1β production in macrophages and may regulate IL-1β maturation by promoting caspase-1. C/EBPβ may be a promising candidate for the prevention and treatment of atherosclerosis

Efficient routing on scale-free networks based on local information

In this letter, we propose a new routing strategy with a single free parameter $\alpha$ only based on local information of network topology. In order to maximize the packets handling capacity of underlying structure that can be measured by the critical point of continuous phase transition from free flow to congestion, the optimal value of $\alpha$ is sought out. By investigating the distributions of queue length on each node in free state, we give an explanation why the delivering capacity of the network can be enhanced by choosing the optimal $\alpha$. Furthermore, dynamic properties right after the critical point are also studied. Interestingly, it is found that although the system enters the congestion state, it still possesses partial delivering capability which do not depend on $\alpha$. This phenomenon suggests that the capacity of the network can be enhanced by increasing the forwarding ability of small important nodes which bear severe congestion.Comment: 4 pages, 7 figure

The Extended Bose Hubbard Model on the Two Dimensional Honeycomb Lattice

We study the extended Bose-Hubbard model on a two-dimensional honeycomb lattice by using large scale quantum Monte Carlo simulations. We present the ground state phase diagrams for both the hard-core case and the soft-core case. For the hard-core case, the transition between $\rho=1/2$ solid and the superfluid is first order and the supersolid state is unstable towards phase separation. For the soft-core case, due to the presence of the multiple occupation, a stable particle induced supersolid (SS-p) phase emerges when $1/2<\rho<1$. The transition from the solid at $\rho=1/2$ to the SS-p is second order with the superfluid density scaling as $\rho_{s} \sim \rho-1/2$. The SS-p has the same diagonal order as the solid at $\rho=1/2$. As the chemical potential increasing further, the SS-p will turn into a solid where two bosons occupying each site of a sublattice through a first order transition. We also calculate the critical exponents of the transition between $\rho=1/2$ solid and superfluid at the Heisenberg point for the hard core case. We find the dynamical critical exponent $z=0.15$, which is smaller than results obtained on smaller lattices. This indicates that $z$ approaches zero in the thermodynamic limit, so the transition is also first order even at the Heisenberg point.Comment: 6pages, 6figure

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background/Aims: Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI. Methods: We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×105), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection. Conclusion: Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features

INTRODUCTION: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. METHODS: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF \u3c 65% (termed as HFrEF, RESULTS: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, CONCLUSION: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology