Prompt Description
Following Roux-en-Y gastric bypass (RYGB) surgery, adipose tissue distribution undergoes significant remodeling, with a substantial decrease in the visceral fat/subcutaneous fat ratio. Subcutaneous fat becomes the primary source of inflammatory factor secretion. Post-RYGB patients exhibit a marked enrichment of CD14⁺ macrophages in subcutaneous fat compared to pre-surgery levels, with this subpopulation abnormally overexpressing HMGB1. HMGB1 selectively promotes the differentiation of bone marrow-derived macrophages (BMMs) into osteoclast precursors (OCPs) via the TLR4 receptor on the macrophage surface. Subsequently, HMGB1 binds to the RAGE receptor on OCP membranes, promoting actin cytoskeleton remodeling and actin ring formation, leading to osteoclast maturation. Further research indicates that RAGE/TLR4 can synergize with RANKL-RANK signaling to upregulate the expression of the key osteoclastogenic gene NFATc1 by activating the NF-κB and p38 MAPK pathways, thereby enhancing differentiation efficiency. To address this potential mechanism, this study proposes to construct engineered exosomes specifically targeting CD14⁺ macrophages to precisely deliver HMGB1-siRNA to adipose tissue macrophages, thereby blocking the transmission of abnormal inflammatory signals to bone tissue.
![```python
import matplotlib.pyplot as plt
import matplotlib.patches as mpatches
from matplotlib.patches import Rectangle, Ellipse, Polygon, FancyArrowPatch
import numpy as np
# Configure Chinese font
plt.rcParams['font.sans-serif'] = ['SimHei']
plt.rcParams['axes.unicode_minus'] = False
fig, ax = plt.subplots(1, 1, figsize=(10, 8))
ax.set_xlim(0, 10)
ax.set_ylim(0, 8)
ax.axis('off')
# 1. Seed germination
ax.add_patch(Rectangle((1, 6), 1.5, 0.3, color='saddlebrown', alpha=0.7, label='MS Medium'))
ax.add_patch(Ellipse((1.5, 6.5), 0.3, 0.2, color='darkgreen', alpha=0.8, label='N. benthamiana seeds'))
ax.text(1, 6.8, '1. Seeds germinate on MS medium', fontsize=10, va='bottom')
# 2. Agrobacterium inoculation
ax.add_patch(Ellipse((4, 6.5), 0.5, 0.3, color='lightblue', alpha=0.7, label='Agrobacterium suspension'))
ax.text(3.2, 6.8, '2. Agrobacterium GV3101 inoculation', fontsize=10, va='bottom')
# Arrow indicating inoculation process
arrow = FancyArrowPatch((2.5, 6.5), (3.7, 6.5),
arrowstyle='->', color='red', linewidth=2)
ax.add_patch(arrow)
# 3. Dark incubation
ax.add_patch(Rectangle((6, 5.8), 2, 1.4, color='black'
```](/_next/image?url=https%3A%2F%2Fpub-8c0ddfa5c0454d40822bc9944fe6f303.r2.dev%2Fai-drawings%2F1TlmQnMxbeuNTbpKoF6eI332tClU3piH%2F3ed380c1-9cc5-4e37-83e6-4c51fb42c6a2%2F26302c86-5b96-456e-b04b-bd25a362e066.png&w=3840&q=75)
