Modeling Multi-wavelength Pulse Profiles of Millisecond Pulsar PSR B1821-24

PSR B1821$-$24 is a solitary millisecond pulsar (MSP) which radiates multi-wavelength pulsed photons. It has complex radio, X-ray and $\gamma$-ray pulse profiles with distinct peak phase-separations that challenge the traditional caustic emission models. Using the single-pole annular gap model with suitable magnetic inclination angle ($\alpha=40^\circ$) and viewing angle ($\zeta=75^\circ$), we managed to reproduce its pulse profiles of three wavebands. It is found that the middle radio peak is originated from the core gap region at high altitudes, and the other two radio peaks are originated from the annular gap region at relatively low altitudes. Two peaks of both X-ray and $\gamma$-ray wavebands are fundamentally originated from annular gap region, while the $\gamma$-ray emission generated from the core gap region contributes somewhat to the first $\gamma$-ray peak. Precisely reproducing the multi-wavelength pulse profiles of PSR B1821$-$24 enables us to understand emission regions of distinct wavebands and justify pulsar emission models.Comment: Accepted for publication in Ap

FGF21 overexpression alleviates VSMC senescence in diabetic mice by modulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with progressive senescence in vascular smooth muscle cells (VSMCs). The vascular protective effect of FGF21 has gradually gained increasing attention, but its role in diabetes-induced vascular senescence needs further investigation. In this study, diabetic mice and primary VSMCs are transfected with an FGF21 activation plasmid and treated with a peroxisome proliferator-activated receptor γ (PPARγ) agonist (rosiglitazone), an NLRP3 inhibitor (MCC950), and a spleen tyrosine kinase (SYK)-specific inhibitor, R406, to detect senescence-associated markers. We find that FGF21 overexpression significantly restores the level of catalase (CAT), vascular relaxation, inhibits the intensity of ROSgreen fluorescence and p21 immunofluorescence, and reduces the area of SA-β-gal staining and collagen deposition in the aortas of diabetic mice. FGF21 overexpression restores CAT, inhibits the expression of p21, and limits the area of SA-β-gal staining in VSMCs under high glucose conditions. Mechanistically, FGF21 inhibits SYK phosphorylation, the production of the NLRP3 dimer, the expression of NLRP3, and the colocalization of NLRP3 with PYCARD (ASC), as well as NLRP3 with caspase-1, to reverse the cleavage of PPARγ, preserve CAT levels, suppress ROSgreen density, and reduce the expression of p21 in VSMCs under high glucose conditions. Our results suggest that FGF21 alleviates vascular senescence by regulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway in diabetic mice