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Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid–induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI. Editor's summary: Acute kidney injury (AKI) is a complication of critically ill patients with COVID-19. Dexamethasone is a synthetic glucocorticoid used to treat severe COVID-19. Zhou et al. combined data from patients who died in association with COVID-19, human tissue, and mouse models of AKI and found that renal tubular epithelial cell (TEC) damage from myoglobinuria resulted in glucocorticoid receptor activation and worse injury. Mice given myoglobinuric injury and dexamethasone treatment had exacerbated TEC damage. Human kidney slices and TEC organoids from both humans and mice corroborated this exacerbated damage. Inhibiting endogenous glucocorticoid production or inactivating the glucocorticoid receptor ameliorated TEC damage in these models. TEC damage was linked to DNA damage and mitochondrial impairment. These data suggest that glucocorticoid receptor activation aggravates renal injury. —Brandon Berry [ABSTRACT FROM AUTHOR]

Summary: Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown.Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize.We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting.Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression. [ABSTRACT FROM AUTHOR]

Birds are sensitive to environmental changes and can drive range shifts rapidly due to their high mobility. Though previous studies have examined the associations between species traits and range shifts, whether species traits could still explain heterogeneity in shift directions remains poorly explored. Here, we compiled new bird records of China from 2000 to 2019 and analyzed species traits associated with apparent shift directions. We collected 350 provincial-level new records of birds belonging to 67 families of 22 orders. Of these, 32 are threatened, with 3 critically endangered, 11 endangered, and 18 vulnerable. Provinces in western China (i.e., Yunnan and Xizang) had relatively higher species richness of new recorded birds; this pattern was also reflected in the phylogenetic diversity we observed. In addition, provinces in northern China (i.e., Tianjin, Shandong, and Beijing) had relatively higher richness-controlled phylogenetic diversity. Phylogenetic overdispersion of new recorded bird communities was observed in 61.29% of provinces (19 of 31). The main shift directions indicated by new bird records were northward (with nearly 50% of birds moving NW, N and NE). Migration, hand-wing index (HWI), body mass, and range size are the four key factors that most significantly influence the shift directions in bird species, suggesting that bird movement toward newly suitable areas varies with species-specific traits. Together, these results demonstrate the importance of considering species ecological traits when predicting shift directions of birds. [ABSTRACT FROM AUTHOR]

Three pairs of enantiomers (1–3)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (5–7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2–5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals. [ABSTRACT FROM AUTHOR]

Zanthoxylum nitidum (Roxb.) DC is a traditional Chinese herb from southern China and its 3–4‐year old roots are used in medicine. However, there is a scarcity of studies on the differences in the content of different regions of the roots, as well as comprehensive evaluations of Z. nitidum from the main areas of production in China. This study used ultra performance liquid chromatography, triple quadrupole tandem mass spectrometry, HPLC, and Fourier‐transform infrared spectroscopy to detect and identify the bioactive components from different parts and eight regions of 4‐year‐old roots of Z. nitidum. Our results revealed that the types and quantities of compounds extracted were similar in root bark and root wood, although the amount of alkaloids in the former was substantially higher. The contents of four alkaloids in samples from Guangdong were higher than those in Guangxi Province. Meanwhile, hierarchical cluster analysis and principal component analysis showed that the samples from different regions were effectively identified and evaluated based on alkaloids and other bioactive substances. Our findings have significant implications for Z. nitidum harvesting and usage, as well as for origin identification, quality evaluation, and sensible use of Z. nitidum resources. [ABSTRACT FROM AUTHOR]