Artemisinin and its derivatives (ARTs) can kill malaria parasites, but its mechanism remains unclear. Haem or iron (HI) was proposed to activate ARTs to produce free radicals that kill malaria parasites. However, our results revealed that adding iron supply did not enhance the antimalarial effect of ARTs but attenuated this effect, strongly suggesting that its free radical effect was not its only antimalarial mechanism. Single-cell RNA sequencing analysis of Plasmodium yoelii 17XNL-infected erythrocytes revealed that the stages most sensitive to ARTs were closely associated with the expression of haem- and iron- related, DNA synthesis-related, antioxidation-related, and pentose-phosphate-pathway-related genes, simultaneously accompanied with the release and utilization of HI. In addition, ARTs were found to combine with haem to form adducts and disturb the normal aggregation of hemozoin in parasites. In particular, adding iron supply antagonized the antimalarial effect of ARTs in vivo and in vitro, strongly suggesting that ARTs trap HI and disturb the requirement of parasites dependent of HI, thereby resulting in the antimalarial effect, which is likely similar to the antimalarial mechanism of iron chelators. Thus, the iron chelator effect with free radical effect renders ARTs the double-kill antimalarial mechanism.
Three dimensional (3D) ultra-structural imaging is an important tool for unraveling the organizational structure of individual chromosomes at various stages of the cell cycle. Performing hitherto uninvestigated ultra-structural analysis of the human genome at prophase, we used serial block-face scanning electron microscopy (SBFSEM) to understand chromosomal architectural organization within 3D nuclear space. Acquired images allowed us to segment, reconstruct, and extract quantitative 3D structural information about the prophase nucleus and the preserved, intact individual chromosomes within it. Our data demonstrate that each chromosome can be identified with its homolog and classified into respective cytogenetic groups. Thereby, we present the first 3D karyotype built from the compact axial structure seen on the core of all prophase chromosomes. The chromosomes display parallel-aligned sister chromatids with familiar chromosome morphologies with no crossovers. Furthermore, the spatial positions of all 46 chromosomes revealed a pattern showing a gene density-based correlation and a neighborhood map of individual chromosomes based on their relative spatial positioning. A comprehensive picture of 3D chromosomal organization at the nanometer level in a single human lymphocyte cell is presented.
With the application of a three-dimensional (3D) characterization technique, serial block-face scanning electron microscopy (SBFSEM), the 3D microstructure of a hydrated cement monomineral, tricalcium silicate (C3S), was measured with nanoscale resolution. The 3D morphologies of anhydrous particles, hydrated products, and capillary pores were visualized. Closed and open pores were discovered inside an anhydrous particle. The size and distribution of both the anhydrous C3S particles and their capillary pores were analyzed quantitatively and the porosity was determined to be 9%. The distribution of pores was found to be in a good agreement with the inner and outer product model of Hu et. al., with an inner shell distance of 860 nm. Considering the spatial resolution of the instrument and the volume of sample measured, most pores in this experiment could be characterized as capillary pores.
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