Escherichia coli contains operons called "addiction modules," encoding toxin and antitoxin, which are responsible for growth arrest and cell death. Here, we demonstrate that MazF toxin encoded by "mazEF addiction module" is a sequence-specific (ACA) endoribonuclease functional only for single-stranded RNA. MazF works as a ribonuclease independent of ribosomes, and is, therefore, functionally distinct from RelE, another E. coli toxin, which assists mRNA cleavage at the A site on ribosomes. Upon induction, MazF cleaves whole cellular mRNAs to efficiently block protein synthesis. Purified MazF inhibited protein synthesis in both prokaryotic and eukaryotic cell-free systems. This inhibition was released by MazE, the labile antitoxin against MazF. Thus, MazF functions as a toxic endoribonuclease to interfere with the function of cellular mRNAs by cleaving them at specific sequences leading to rapid cell growth arrest and cell death. The role of such endoribonucleases may have broad implication in cell physiology under various growth conditions.
The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201901673.Low-dimensional Ruddlesden-Popper perovskites (RPPs) exhibit excellent stability in comparison with 3D perovskites; however, the relatively low power conversion efficiency (PCE) limits their future application. In this work, a new fluorine-substituted phenylethlammonium (PEA) cation is developed as a spacer to fabricate quasi-2D (4FPEA) 2 (MA) 4 Pb 5 I 16 (n = 5) perovskite solar cells. The champion device exhibits a remarkable PCE of 17.3% with a J sc of 19.00 mA cm −2 , a V oc of 1.16 V, and a fill factor (FF) of 79%, which are among the best results for low-dimensional RPP solar cells (n ≤ 5). The enhanced device performance can be attributed as follows: first, the strong dipole field induced by the 4-fluoro-phenethylammonium (4FPEA) organic spacer facilitates charge dissociation. Second, fluorinated RPP crystals preferentially grow along the vertical direction, and form a phase distribution with the increasing n number from bottom to the top surface, resulting in efficient charge transport. Third, 4FPEA-based RPP films exhibit higher film crystallinity, enlarged grain size, and reduced trap-state density. Lastly, the unsealed fluorinated RPP devices demonstrate superior humidity and thermal stability. Therefore, the fluorination of the long-chain organic cations provides a feasible approach for simultaneously improving the efficiency and stability of low-dimensional RPP solar cells.
Perovskite Solar CellsOrganic-inorganic hybrid perovskites have attracted tremendous attention due to their high absorption coefficients, [1] high charge carrier mobility, [2] high defect tolerance, [3] and long diffusion lengths. [4] Although the power conversion efficiency (PCE) of perovskite solar cells (PSCs) has reached 23.32% in the past few years, the intrinsic material instability of 3D perovskites still remain unresolved, which hinder the future commercialization of perovskite solar cells. [5] Compared
MazF is an Escherichia coli toxin that is highly conserved among the prokaryotes and plays an important role in growth regulation. When MazF is induced, protein synthesis is effectively inhibited. However, the mechanism of MazF action has been controversial. Here we unequivocally demonstrate that MazF is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. We then demonstrate its enzymatic specificity using short RNA substrates. MazF cleaves RNA at the 5-end of ACA sequences, yielding a 2,3-cyclic phosphate at one side and a free 5-OH group at the other. Using DNA-RNA chimeric substrates containing XACA, the 2-OH group of residue X was found absolutely essential for MazF cleavage, whereas all the other residues may be deoxyriboses. Therefore, MazF exhibits exquisite site specificity and has utility as an RNArestriction enzyme for RNA structural studies or as an mRNA interferase to regulate cell growth in prokaryotic and eukaryotic cells.
The synthesis of well-defined and complex hollow structures via a simple method is still a major challenge. In this work, a facile and controllable "multi-interface transformation" approach for preparation of monodisperse multi-shelled periodic mesoporous organosilica (PMO) hollow spheres has been established by a one-step hydrothermal treatment of successively grown organosilica particles. The multi-shelled PMO hollow spheres have inorganic-organic hybrid frameworks, controllable number (1-4) of shells, high surface area (∼805 m(2)/g), accessible ordered mesochannels (∼3.2 nm), large pore volume (1.0 cm(3)/g), and uniform and tunable diameter (300-550 nm), chamber size (4-54 nm), and shell thickness (10-30 nm). In addition, various organic groups (alkyl, aromatic, and heteroelement fragments) are successfully incorporated into the multi-shelled PMO hollow spheres by successively adding different bridged organosilica precursors. Notably, the distribution of different kinds of organic groups in the multi-shelled PMO hollow spheres can be precisely controlled, showing great potential for future applications. We propose that the formation of the multi-shelled PMO hollow structures is ascribed to the creation of multiple highly cross-linked organosilica interfaces, providing a new and interesting fundamental principle for PMO materials. Due to their unique structure and frameworks, triple-shelled ethane-bridged PMO hollow spheres were successfully loaded with an anti-cancer drug doxorubicin and perfluoropentane gas, which present excellent effects in the killing of cancer cells and ultrasound imaging. It is expected that the multi-interface transformation strategy provides a simple, controllable, versatile, and template-free method for preparation of various multifunctional PMOs for different applications.
Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m·g), well-defined mesopores (2.6-3.2 nm), and large pore volumes (0.33-0.75 m·g). Most importantly, the HPMO nanocapsules simultaneously have large hollow cavities (164-270 nm), thin shell thicknesses (20-38 nm), and abundant organic moiety in the shells, which endow a lower Young's modulus (E) of 3.95 MPa than that of solid PMO nanoparticles (251 MPa). The HPMOs with low E are intrinsically flexible and deformable in the solution, which has been well-characterized by liquid cell electron microscopy. More interestingly, it is found that the deformable HPMOs can easily enter into human breast cancer MCF-7 cells via a spherical-to-oval morphology change, resulting in a 26-fold enhancement in cellular uptake (43.1% cells internalized with nanocapsules versus 1.65% cells with solid counterparts). The deformable HPMO nanocapsules were further loaded with anticancer drug doxorubicin (DOX), which shows high killing effects for MCF-7 cells, demonstrating the promise for biomedical applications.
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