再生基因家族成员4 (Regenerating Islet-derived Family Member 4, REG4)是一种分泌性蛋白,属于钙依赖性C型凝集素超家族。其在正常胃肠道组织中局限表达,主要功能涉及黏膜保护、增殖与分化。近年研究发现,REG4在结肠癌中呈现显著的高...再生基因家族成员4 (Regenerating Islet-derived Family Member 4, REG4)是一种分泌性蛋白,属于钙依赖性C型凝集素超家族。其在正常胃肠道组织中局限表达,主要功能涉及黏膜保护、增殖与分化。近年研究发现,REG4在结肠癌中呈现显著的高表达,并通过激活多条关键信号通路,在肿瘤细胞的增殖、凋亡逃逸、侵袭、转移、化疗抵抗以及干细胞特性维持中发挥核心作用。本综述系统阐述了REG4的分子结构与生物学功能,详细分析了其在结肠癌中异常表达的调控机制,并深入探讨了其通过EGFR/Akt、MAPK、STAT3等通路促进肿瘤恶性进展的分子机理。此外,本文重点评述了REG4作为结肠癌诊断、预后判断和疗效预测的新型生物标志物的巨大潜力,以及其作为创新治疗靶点的最新研究进展。最后,我们对当前研究的挑战和未来转化医学的方向进行了展望,旨在为结肠癌的精准医疗提供新的理论依据和策略方向。展开更多
This study discusses the sensitivity of convective parameterization schemes（CPSs） in the Regional Climate Model（version 4.3）（Reg CM4.3） over East/South Asia. The simulations using different CPSs in Reg CM are co...This study discusses the sensitivity of convective parameterization schemes（CPSs） in the Regional Climate Model（version 4.3）（Reg CM4.3） over East/South Asia. The simulations using different CPSs in Reg CM are compared to discover a suitable scheme for this region, as the performance of different schemes is greatly influenced by region and seasonality. Over Southeast China and the Bay of Bengal, the Grell scheme exhibits the lowest RMSEs of summer precipitation compared to observed data. Moreover, the Emanuel over land and Grell over ocean（ELGO） scheme enhances the simulation, in comparison with any single CPS（Grell/Emanuel） over Western Ghats, Sri Lanka, and Southeast India. Over the Huang–Huai–Hai Plain（3H） and Tibetan Plateau（TP） regions of China, the Tiedtke scheme simulates the more reasonable summer precipitation with high correlation coefficient and comparable amplitude. Especially, it reproduces a minimum convective precipitation bias of 8 mm d^-1and the lowest RMSEs throughout the year over East/South Asia. Furthermore, for seasonal variation of precipitation, the Tiedtke scheme results are closer to the observed data over the 3H and TP regions. However, none of the CPSs is able to simulate the seasonal variation over North Pakistan（NP）. In comparison with previous research, the results of this study support the Grell scheme over South Asia. However, the Tiedtke scheme shows superiority for the 3H, TP and NP regions. The thicker PBL, less surface latent heat flux, the unique ability of deep convection and the entrainment process in the Tiedtke scheme are responsible for reducing the wet bias.展开更多
文摘再生基因家族成员4 (Regenerating Islet-derived Family Member 4, REG4)是一种分泌性蛋白,属于钙依赖性C型凝集素超家族。其在正常胃肠道组织中局限表达,主要功能涉及黏膜保护、增殖与分化。近年研究发现,REG4在结肠癌中呈现显著的高表达,并通过激活多条关键信号通路,在肿瘤细胞的增殖、凋亡逃逸、侵袭、转移、化疗抵抗以及干细胞特性维持中发挥核心作用。本综述系统阐述了REG4的分子结构与生物学功能,详细分析了其在结肠癌中异常表达的调控机制,并深入探讨了其通过EGFR/Akt、MAPK、STAT3等通路促进肿瘤恶性进展的分子机理。此外,本文重点评述了REG4作为结肠癌诊断、预后判断和疗效预测的新型生物标志物的巨大潜力,以及其作为创新治疗靶点的最新研究进展。最后,我们对当前研究的挑战和未来转化医学的方向进行了展望,旨在为结肠癌的精准医疗提供新的理论依据和策略方向。
基金supported by the Knowledge Innovation Program of the Chinese Academy of Sciences (KZCX2EW-QN208)a project of the National Natural Science Foundation of China (Grant No. 41275082)+1 种基金the National Basic Research Program of China (Grant Nos. 2010CB428502 and 2011CB952003)the R&D Special Fund for Public Welfare Industry (meteorology) of the Ministry of Finance and the Ministry of Science and Technology (GYHY201006014-04)
文摘This study discusses the sensitivity of convective parameterization schemes（CPSs） in the Regional Climate Model（version 4.3）（Reg CM4.3） over East/South Asia. The simulations using different CPSs in Reg CM are compared to discover a suitable scheme for this region, as the performance of different schemes is greatly influenced by region and seasonality. Over Southeast China and the Bay of Bengal, the Grell scheme exhibits the lowest RMSEs of summer precipitation compared to observed data. Moreover, the Emanuel over land and Grell over ocean（ELGO） scheme enhances the simulation, in comparison with any single CPS（Grell/Emanuel） over Western Ghats, Sri Lanka, and Southeast India. Over the Huang–Huai–Hai Plain（3H） and Tibetan Plateau（TP） regions of China, the Tiedtke scheme simulates the more reasonable summer precipitation with high correlation coefficient and comparable amplitude. Especially, it reproduces a minimum convective precipitation bias of 8 mm d^-1and the lowest RMSEs throughout the year over East/South Asia. Furthermore, for seasonal variation of precipitation, the Tiedtke scheme results are closer to the observed data over the 3H and TP regions. However, none of the CPSs is able to simulate the seasonal variation over North Pakistan（NP）. In comparison with previous research, the results of this study support the Grell scheme over South Asia. However, the Tiedtke scheme shows superiority for the 3H, TP and NP regions. The thicker PBL, less surface latent heat flux, the unique ability of deep convection and the entrainment process in the Tiedtke scheme are responsible for reducing the wet bias.
