Nitric oxide (NO) and ethylene respond to biotic and abiotic stresses through either similar or independent processes. This study examines the mechanism underlying the effects of NO and ethylene on promoting root hair development in Arabidopsis under magnesium (Mg) deficiency. The interaction between NO and ethylene in the regulation of Mg deficiency-induced root hair development was investigated using NO- and ethylene-related mutants and pharmacological methods. Mg deficiency triggered a burst of NO and ethylene, accompanied by a stimulated development of root hairs. Interestingly, ethylene facilitated NO generation by activation of both nitrate reductase and nitric oxide synthase-like (NOS-L) in the roots of Mg-deficient plants. In turn, NO enhanced ethylene synthesis through stimulating the activities of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and ACC synthase (ACS). These two processes constituted an NO-ethylene feedback loop. Blocking either of these two processes inhibited the stimulation of root hair development under Mg deficiency. In conclusion, we suggest that Mg deficiency increases the production of NO and ethylene in roots, each influencing the accumulation and role of the other, and thus these two signals interactively regulate Mg deficiency-induced root hair morphogenesis.

Pathology is the medical specialty concerned with the study of the disease nature and causes, playing a key role in bridging basic researches and clinical medicine. In the course of development, pathology has significantly expanded our understanding of disease, and exerted enormous impact on the management of patients. However, challenges facing pathology, the inherent invasiveness of pathological practice and the persistent concerns on the sample representativeness, constitute its limitations. Molecular imaging is a noninvasive technique to visualize, characterize, and measure biological processes at the molecular level in living subjects. With the continuous development of equipment and probes, molecular imaging has enabled an increasingly precise evaluation of pathophysiological changes. A new pathophysiology visualization system based on molecular imaging is forming and shows the great potential to reform the pathological practice. Several improvements in “trans-,” including trans-scale, transparency, and translation, would be driven by this new kind of pathological practice. Pathological changes could be evaluated in a trans-scale imaging mode; tissues could be transparentized to better present the underlying pathophysiological information; and the translational processes of basic research to the clinical practice would be better facilitated. Thus, transpathology would greatly facilitate in deciphering the pathophysiological events in a multiscale perspective, and supporting the precision medicine in the future.

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GTPBP3 is a highly conserved tRNA modifying enzyme for the biosynthesis of τm 5 U at the wobble position of mitochondrial tRNA Glu , tRNA Gln , tRNA Lys , tRNA Trp and tRNA Leu(UUR) . The previous investigations showed that GTPBP3 mutations were associated with hypertrophic cardiomyopathy (HCM). However, the pathophysiology of GTPBP3 deficiency remains elusively. Using the gtpbp3 knockout zebrafish generated by CRISPR/Cas9 system, we demonstrated the aberrant mitochondrial tRNA metabolism in gtpbp3 knock-out zebrafish. The deletion of gtpbp3 may alter functional folding of tRNA, indicated by conformation changes and sensitivity to S1-mediated digestion of tRNA Glu , tRNA Lys , tRNA Trp and tRNA Leu(UUR) . Strikingly, gtpbp3 knock-out zebrafish displayed the global increases in the aminoacylated efficiencies of mitochondrial tRNAs. The aberrant mitochondrial tRNA metabolisms impaired mitochondrial translation, produced proteostasis stress and altered activities of respiratory chain complexes. These mitochondria dysfunctions caused the alterations in the embryonic heart development and reduced fractional shortening of ventricles in mutant zebrafish. Notably, the gtpbp3 knock-out zebrafish exhibited hypertrophy of cardiomyocytes and myocardial fiber disarray in ventricles. These cardiac defects in the gtpbp3 knock-out zebrafish recapitulated the clinical phenotypes in HCM patients carrying the GTPBP3 mutation(s). Our findings highlight the fundamental role of defective nucleotide modifications of tRNAs in mitochondrial biogenesis and their pathological consequences in hypertrophic cardiomyopathy.