REGγ drives Lgr5+ stem cells to potentiate radiation induced intestinal regeneration.

Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a marker of intestinal stem cells (ISCs), is considered to play key roles in tissue homoeostasis and regeneration after acute radiation injury. However, the activation of Lgr5 by integrated signaling pathways upon radiation remains poorly understood. Here, we show that irradiation of mice with whole-body depletion or conditional ablation of REGγ in Lgr5+ stem cell impairs proliferation of intestinal crypts, delaying regeneration of intestine epithelial cells. Mechanistically, REGγ enhances transcriptional activation of Lgr5 via the potentiation of both Wnt and Hippo signal pathways. TEAD4 alone or cooperates with TCF4, a transcription factor mediating Wnt signaling, to enhance the expression of Lgr5. Silencing TEAD4 drastically attenuated ß-catenin/TCF4 dependent expression of Lgr5. Together, our study reveals how REGγ controls Lgr5 expression and expansion of Lgr5+ stem cells in the regeneration of intestinal epithelial cells. Thus, REGγ proteasome appears to be a potential therapeutic target for radiation-induced gastrointestinal disorders.

The silver linings of mercury: Reconsideration of its impacts on living organisms from a multi-timescale perspective.

Research on mercury (Hg), a naturally occurring element in Earth's lithosphere, has been extremely hot in the past few decades due to the outbreak of a series of disastrous poisoning incidents. However, such studies might provide us a biased view towards Hg if no thorough review about its long-term effects on living organisms from a multi-timescale perspective was performed. Hg might have played a mysterious role in critical intervals (e.g., mass extinction and oceanic anoxia events) in several geologic periods due to the elevated Hg levels induced by volcanism whereas it has long been used for various purposes in human history. Therefore, it is necessary to go through previous studies and historical records of different timescales (100 to 106 yr). In this work, we conducted a thorough review of Hg knowledge at three different timescales, i.e., geologic periods (106 yr), human history (103 yr), and contemporary history (100 yr), summarizing recent advances and indicated potential research gaps. By doing so, we demonstrated that it is possible to achieve safe and sustainable Hg applications despite the current Hg crisis. However, such silver linings depend on a better understanding of ecosystem dynamics. Besides, considering the possible dire consequences of erupted Hg levels as suggested in geological periods, swift actions to mitigate the impacts of anthropogenic activities on the Hg cycle will be another key point. Overall, this review presented a unique perspective of Hg combining different timescales, shedding light on the importance of a better understanding of the global ecosystem as a whole and maintaining the sustainability of planet Earth in the future.

Mapping Novel Biomarkers of Liver Injury by Tissue Proteomic Analysis.

Liver damage is a dynamic process, and evaluation of liver injury degree is the key step in disease diagnosis. However, few common markers among different types of liver injury have been reported. Herein, we generated three liver injury mouse models, including Con A-induced, CCl4-injected, and subjected bile duct ligation mouse models, to simulate different types of liver damage in humans and then performed a label-free mass spectrometry to identify differentially expressed proteins in liver tissues. Interestingly, two proteins, G3BP and ABCC6, were conserved regulated in different liver injury models and are proposed to be biomarkers in liver injury, with G3BP upregulated and ABCC6 downregulated. Overall, our study identified two novel biomarkers of liver injury, and they might be used as potential drug targets of liver damage research studies.