Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a centromere-specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

Deuteration-enhanced neutron contrasts to probe amorphous domain sizes in organic photovoltaic bulk heterojunction films.

An organic photovoltaic bulk heterojunction comprises of a mixture of donor and acceptor materials, forming a semi-crystalline thin film with both crystalline and amorphous domains. Domain sizes critically impact the device performance; however, conventional X-ray scattering techniques cannot detect the contrast between donor and acceptor materials within the amorphous intermixing regions. In this study, we employ neutron scattering and targeted deuteration of acceptor materials to enhance the scattering contrast by nearly one order of magnitude. Remarkably, the PM6:deuterated Y6 system reveals a new length scale, indicating short-range aggregation of Y6 molecules in the amorphous intermixing regions. All-atom molecular dynamics simulations confirm that this short-range aggregation is an inherent morphological advantage of Y6 which effectively assists charge extraction and suppresses charge recombination as shown by capacitance spectroscopy. Our findings uncover the amorphous nanomorphology of organic photovoltaic thin films, providing crucial insights into the morphology-driven device performance.

Soil bacterial microbiota predetermines rice yield in reclaiming saline-sodic soils leached with brackish ice.

BACKGROUND: Saline-sodic lands threaten the food supply and ecological security in the western Songnen Plain of northeast China, and the gypsum is commonly adopted for restoration. However, the dynamics of soil bacterial community and the correlation with crop yield during restoring processes remain poorly understood. Here, we elucidated the soil chemical properties and bacterial communities and their associations with rice yield under different flue gas desulphurization gypsum (FGDG) application rates combined with brackish ice leaching. RESULTS: The increased application rate of FGDG generally improved soil reclamation effects, as indicated by soil chemical properties, bacterial diversity, and rice yield. Compared with fresh ice irrigation, the rice yield in brackish ice treatment increased by 15.84%, and the soil alkalinity and sodium adsorption ratio (SAR) decreased by 35.19% and 10.30%, respectively. The bacterial alpha diversity significantly correlated and predicted rice yield as early as brackish ice melt, suggesting the bacterial diversity was a sensitive indicator in predicting rice yield. Meanwhile, the bacterial communities in the control possessed a high abundance of oligotrophic Firmicutes, while eutrophic bacterial taxa (e.g. Proteobacteria) were enriched after brackish water irrigation and FGDG application. Moreover, we also established a Random Forest model and identified a bacterial consortium that explained an 80.0% variance of rice yield. CONCLUSION: Together, our results highlight the reclaiming effect of brackish ice in the saline-sodic field and demonstrate the sensitivity and importance of the soil bacterial community in predicting crop yield, which would provide essential knowledge on the soil quality indication and bio-fertilizer development for soil reclamation. © 2021 Society of Chemical Industry.