RESUMEN
Background: Aberrant autoreactive B cell responses contribute to the pathogenesis of systemic lupus erythematosus (SLE). Currently, there is no safe and effective drug for intervention of SLE. Quinazoline derivative (N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine, QNZ) is a NF-κB inhibitor and has potent anti-inflammatory activity. However, it is unclear whether QNZ treatment can modulate B cell activation and SLE severity. Methods: Splenic CD19+ B cells were treated with QNZ (2, 10, or 50 nM) or paeoniflorin (200 µM, a positive control), and their activation and antigen presentation function-related molecule expression were examined by flow cytometry. MRL/lpr lupus-prone mice were randomized and treated intraperitoneally with vehicle alone, 0.2 mg/kg/d QNZ or 1 mg/kg/d FK-506 (tacrolimus, a positive control) for 8 weeks. Their body weights and clinical symptoms were measured and the frequency of different subsets of splenic and lymph node activated B cells were quantified by flow cytometry. The degrees of kidney inflammation and glycogen deposition were examined by hematoxylin and eosin (H&E) and PAS staining. The levels of serum autoantibodies and renal IgG, complement C3 deposition were examined by ELISA and immunofluorescence. Results: QNZ treatment significantly inhibited the activation and antigen presentation-related molecule expression of B cells in vitro. Similarly, treatment with QNZ significantly mitigated the SLE activity by reducing the frequency of activated B cells and plasma cells in MRL/lpr mice. Conclusion: QNZ treatment ameliorated the severity of SLE in MRL/lpr mice, which may be associated with inhibiting B cell activation, and plasma cell formation. QNZ may be an excellent candidate for the treatment of SLE and other autoimmune diseases.
RESUMEN
It is common for visitors to have rich and varied experiences in the limited space of a classical Chinese garden. This leads to the sense that the garden's scale is much larger than it really is. A main reason for this perceptual bias is the gardener's manipulation of visual information. Most studies have discussed this phenomenon in terms of qualitative description with fragmented perspectives taken from static points, without considering ambient visual information or continuously changing observation points. A general question arises, then, on why depth perception can vary from one observation point to another along a garden path. To better understand the spatial experience in classical Chinese gardens, this study focused on variations in perceived depth among different observation points and aimed to identify influential visual information through psychophysical experimentation. As stimuli for the experiment, panoramic photos of Liu garden were taken from three positions at Lvyin Pavilion. Considering the effects of pictorial visual cues on depth perception, the photos were processed to create 18 kinds of stimuli (six image treatments * three positions). Two tasks were presented to the participants. In Task 1, 71 participants were asked to rate the depth value of the garden using the magnitude estimation method in a cave automatic virtual environment (CAVE). Statistical analysis of Task 1 revealed that depth values differed significantly among different viewpoints. In Task 2, participants were asked to compare 18 stimuli and 3D images presented on three connected monitors and to judge the depth of the garden using the adjustment method. The results of Task 2 again showed that depth values differed significantly among different viewpoints. In both tasks, ambient information (i.e., the perspective of interior space) significantly influenced depth perception.