Muramyl dipeptide (MDP) is the minimal essential structural unit responsible for the immunoadjuvant activity of peptidoglycan. As well as bone-resorbing factors such as 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) and PGE2, LPS and IL-1α stimulate osteoclast formation in mouse cocultures of primary osteoblasts and hemopoietic cells. MDP alone could not induce osteoclast formation in the coculture, but enhanced osteoclast formation induced by LPS, IL-1α, or TNF-α but not 1α,25(OH)2D3 or PGE2. MDP failed to enhance osteoclast formation from osteoclast progenitors induced by receptor activator of NF-κB ligand (RANKL) or TNF-α. MDP up-regulated RANKL expression in osteoblasts treated with LPS or TNF-α but not 1α,25(OH)2D3. Osteoblasts expressed mRNA of nucleotide-binding oligomerization domain 2 (Nod2), an intracellular sensor of MDP, in response to LPS, IL-1α, or TNF-α but not 1α,25(OH)2D3. Induction of Nod2 mRNA expression by LPS but not by TNF-α in osteoblasts was dependent on TLR4 and MyD88. MDP also enhanced TNF-α-induced osteoclast formation in cocultures prepared from Toll/IL-1R domain-containing adapter protein (TIRAP)-deficient mice through the up-regulation of RANKL mRNA expression in osteoblasts, suggesting that TLR2 is not involved in the MDP-induced osteoclast formation. The depletion of intracellular Nod2 by small interfering RNA blocked MDP-induced up-regulation of RANKL mRNA in osteoblasts. LPS and RANKL stimulated the survival of osteoclasts, and this effect was not enhanced by MDP. These results suggest that MDP synergistically enhances osteoclast formation induced by LPS, IL-1α, and TNF-α through RANKL expression in osteoblasts, and that Nod2-mediated signals are involved in the MDP-induced RANKL expression in osteoblasts.
Solid
mixing dynamics is of vital important to the processing rate,
achievable homogeneity and product quality in the related industries
of granular material. In this paper, solid mixing behaviors within
a baffle-type internally circulating fluidized bed (ICFB) are numerically
investigated using a three-dimensional computational fluid dynamics-discrete
element method (CFD-DEM), in which the gas motion is modeled by means
of large eddy simulation (LES) while the solid kinematics is handled
by a soft-sphere model. On the basis of the simulation results, typical
snapshots of granular mixing dynamics in the bed are extracted to
reveal the mixing process of different initial segregation conditions.
The mixing quality, which is described by Lacey mixing index, is evaluated.
Meanwhile, the solid circulation pattern is illustrated by tracking
tracer positions both in the three-dimensional bed and along the horizontal
and vertical directions as simulation time advances. Furthermore,
the influence of different parameters, such as sampling grid dimension,
bed aeration setup, diameter and density of the solid, and the gap
height beneath the baffle, on the mixing behaviors are also investigated.
The results show that macroscopic circulation of solid plays a dominate
role in the mixing process of the bed. Judging by the tracer trajectory
with time, a better transverse mixing can be obtained, and the mixing
mechanisms are further analyzed. Besides, it is found that mixing
rate and degree are insensitive to the sampling grid size and a nice
mixing level can be obtained within seconds providing enough aeration
to the bed and a proper gap height. Meanwhile, lighter and smaller
particles possess better mixing ability, as they are easier to fluidize.
Furthermore, this ICFB exhibits additional potentials in solid mixing
compared with the corresponding fluidized bed.
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