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The evolutionary outcomes of high elevation adaptation have been extensively described. However, whether widely distributed high elevation endemic animals adopt uniform mechanisms during adaptation to different elevational environments remains unknown, especially with respect to extreme high elevation environments. To explore this, we analysed the phenotypic and genomic data of seven populations of plateau zokor (Myospalax baileyi) along elevations ranging from 2,700 to 4,300 m. Based on whole-genome sequencing data and demographic reconstruction of the evolutionary history, we show that two populations of plateau zokor living at elevations exceeding 3,700 m diverged from other populations nearly 10,000 years ago. Further, phenotypic comparisons reveal stress-dependent adaptation, as two populations living at elevations exceeding 3,700 m have elevated ratios of heart mass to body mass relative to other populations, and the highest population (4,300 m) displays alterations in erythrocytes. Correspondingly, genomic analysis of selective sweeps indicates that positive selection might contribute to the observed phenotypic alterations in these two extremely high elevation populations, with the adaptive cardiovascular phenotypes of both populations possibly evolving under the functional constrains of their common ancestral population. Taken together, phenotypic and genomic evidence demonstrates that heterogeneous stressors impact adaptations to extreme elevations and reveals stress-dependent and genetically constrained adaptation to hypoxia, collectively providing new insights into the high elevation adaptation., (© 2021 John Wiley & Sons Ltd.)

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual‐mode NIR fluorescence and 19F MRI agent, FCy7‐NO2, is proposed for imaging tumor hypoxia. We show that FCy7‐NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift‐sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue‐depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment. [ABSTRACT FROM AUTHOR]

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A bimodal imaging probe FCy7‐NO2 was applied to image nitroreductase overexpressed by lung cancer in vivo, as reported by Xin Zhou and co‐workers in their Research Article (e202213495). Integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase over a broad concentration range without tissue‐depth limit. [ABSTRACT FROM AUTHOR]