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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2024 Vol.25 No.9 P.796-799
Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes
Abstract: Type 1 diabetes (T1D) is a T lymphocyte-mediated autoimmune disease caused by pancreatic β-cell destruction, which eventually leads to reduced insulin level and increased blood glucose level (Syed, 2022). As a multifactorial disease, T1D is characterized by a genetic predisposition associated with various environmental and cellular elements (Syed, 2022). Pancreatic β cells have long been considered the “innocent victims” in T1D pathogenesis since the pancreas is attacked by the immune cells, resulting in a process known as insulitis, in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory cytokines. However, growing evidence suggests that various β-cell stresses, dysfunction, and death contribute to T1D pathogenesis, as it has been observed that β-cell dysfunction in autoantibody-positive (Aab+) individuals exists long before T1D diagnosis (Evans-Molina et al., 2018).
Key words: Type 1 diabetes (T1D); Senescence; Unfolded protein response (UPR); Pancreatic β cells
机构：1西南交通大学，高速铁路线路工程教育部重点实验室，中国成都，610031；2中国五冶集团有限公司，中国成都，610063
目的：无砟轨道现浇混凝土部件，尤其是双块式轨道整体现浇道床，在材料不良、环境不利、施工不当等多种因素影响下，早期开裂问题频发。本文旨在建立一个更为完善的早期道床开裂风险预测模型，在此基础上研究早期道床多场时变行为和开裂机理，探寻早期道床开裂风险影响规律并提出合理的开裂风险管控措施。
创新点：1.建立更完善的早期道床开裂风险预测模型，且模型假设条件更少，准确性更高，适用场景更全面；2.系统分析道床早期多场耦合时变规律和开裂机理；3.揭示材料、环境以及施工三类因素对混凝土道床早期开裂风险的影响规律，并提出了道床早期开裂控制措施。
方法：1.通过理论推导，统一混凝土早期到成型全过程的水化-热-湿-力耦合多场控制方程，并建立早期道床开裂风险预测模型；2.通过数值模拟，得到道床早期多场耦合时变规律和开裂机理，并揭示不同因素对混凝土道床早期开裂风险的影响规律。
结论：1.在典型工况条件下，在水化场方面，道床最大水化速率出现在浇筑后约7.0 h；道床终凝点在浇筑后约9.5 h；道床水化在第7 d的水化进程可达最终水化度的90%。在温度场方面，对流换热和太阳辐射是影响道床早期温度场的主要环境因素；道床表层最高温度浇筑后约16.0 h达到最大值，比入模温度高约15.0 °C。在湿度场方面，早期道床内双块式轨枕附件存在局部不均匀湿度区域。在力场方面，约在第1.25 d，轨枕四周新老混凝土结合面开裂的风险系数已超过1.00；在第7 d，轨枕附近道床八字形裂纹的开裂风险达到最大，风险系数约为0.75。2.温度变形是道床表层开裂的主导因素，也是道床板底开裂的主要驱动力；如果不考虑道床混凝土早期徐变，会大幅度高估开裂风险，因此建模时应当考虑徐变的影响。3.综合性的早期道床开裂风险控制措施方面，建议按照优先级降低的顺序（水化热→优化放热峰值时刻→增强保温措施→选择合理浇筑时刻→控制入模温度），进行早期道床混凝土开裂控制。
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DOI:
10.1631/jzus.B2400013
CLC number:
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On-line Access:
2024-08-27
Received:
2023-10-17
Revision Accepted:
2024-05-08
Crosschecked:
2024-09-23