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生物醫學
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Roux-en-Y胃繞道手術 (RYGB) 後，脂肪組織分布發生顯著重塑，內臟脂肪/皮下脂肪比例大幅降低。皮下脂肪成為炎症因子分泌的主要來源。與術前水平相比，RYGB術後患者皮下脂肪中CD14⁺巨噬細胞顯著富集，且該亞群異常過度表達HMGB1。HMGB1選擇性地促進骨髓來源巨噬細胞 (BMMs) 分化為破骨細胞前體 (OCPs)，途徑是透過巨噬細胞表面的TLR4受體。隨後，HMGB1與OCP膜上的RAGE受體結合，促進肌動蛋白骨架重塑和肌動蛋白環形成，進而導致破骨細胞成熟。進一步研究表明，RAGE/TLR4可與RANKL-RANK信號通路協同作用，透過激活NF-κB和p38 MAPK通路，上調關鍵破骨細胞生成基因NFATc1的表達，從而提高分化效率。為了解決這種潛在機制，本研究擬構建特異性靶向CD14⁺巨噬細胞的工程化外泌體，以精準地將HMGB1-siRNA遞送至脂肪組織巨噬細胞，從而阻斷異常炎症信號向骨組織的傳遞。
![```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)
