MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by CLIP-seq, functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm.

Oxidative stress is associated with many acute and chronic inflammatory diseases, yet limited treatment is currently available clinically. The development of enzyme-mimicking nanomaterials (nanozymes) with good reactive oxygen species (ROS) scavenging ability and biocompatibility is a promising way for the treatment of ROS-related inflammation. Herein we report a simple and efficient one-step development of ultrasmall Cu5.4O nanoparticles (Cu5.4O USNPs) with multiple enzyme-mimicking and broad-spectrum ROS scavenging ability for the treatment of ROS-related diseases. Cu5.4O USNPs simultaneously possessing catalase-, superoxide dismutase-, and glutathione peroxidase-mimicking enzyme properties exhibit cytoprotective effects against ROS-mediated damage at extremely low dosage and significantly improve treatment outcomes in acute kidney injury, acute liver injury and wound healing. Meanwhile, the ultrasmall size of Cu5.4O USNPs enables rapid renal clearance of the nanomaterial, guaranteeing the biocompatibility. The protective effect and good biocompatibility of Cu5.4O USNPs will facilitate clinical treatment of ROS-related diseases and enable the development of next-generation nanozymes.

Even though the power conversion efficiency (PCE) of rigid perovskite solar cells is increased to 22.7%, the PCE of flexible perovskite solar cells (F-PSCs) is still lower. Here, a novel dimethyl sulfide (DS) additive is developed to effectively improve the performance of the F-PSCs. Fourier transform infrared spectroscopy reveals that the DS additive reacts with Pb to form a chelated intermediate, which significantly slows down the crystallization rate, leading to large grain size and good crystallinity for the resultant perovskite film. In fact, the trap density of the perovskite film prepared using the DS additive is reduced by an order of magnitude compared to the one without it, demonstrating that the additive effectively retards transformation kinetics during the thin film formation process. As a result, the PCE of the flexible devices increases to 18.40%, with good mechanical tolerance, the highest reported so far for the F-PSCs. Meanwhile, the environmental stability of the F-PSCs significantly enhances by 1.72 times compared to the device without the additive, likely due to the large grain size that suppresses perovskite degradation at grain boundaries. The present strategy will help guide development of high efficiency F-PSCs for practical applications.

Fullerene derivative, such as [6,6]-phenyl C61 butyric acid methyl ester (PCBM), is widely used as an electron-transport layer (ETL) in inverted perovskite solar cell (PSC). However, its low electron mobility, complexity in achieving quality film formation, and severe nonradiative recombination at perovskite/PCBM interface due to the large electron capture region, lead to lower efficiency for inverted PSCs compared to the normal structures. Herein, we demonstrate an effective and practical strategy to overcome these challenges. Conjugated n-type polymeric materials are mixed together with PCBM to form a homogeneous bulk-mixed (HBM) continuous film with high electron mobility and suitable energy level. HBM film is found to completely cap the perovskite surface to enhance the electron extraction. The critical electron capture radius of the HBM decreases to 12.52 nm from 14.89 nm of PCBM due to the large relative permittivity, resulting in reduced nonradiative recombination at perovskite/ HBM interface. The efficiency of inverted PSCs with HBM ETLs exceeds 20.6% with a high fill factor of 0.82. Further, the stability of devices is improved owing to the high hydrophobicity of the HBM ETLs. Under ambient air condition after 45 days, the efficiency of inverted PSCs based on HBM remains 80% of the initial value. This is significantly higher than the control devices which retain only 48% of the initial value under similar aging conditions. We believe these breakthroughs in improving efficiency and stability of inverted PSCs will expedite their transition.

MicroRNA (miRNA) are well known to target 3’ untranslated regions (3’UTR) in mRNAs to silence gene expression at post-transcriptional levels. Multiple reports have also indicated the capability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function in a similar mechanism(s) regardless of the location of their action sites. We herein report a class of miRNA recognition elements (MREs) that exclusively function in CDS regions in humans. Through functional and mechanistic characterization of these “unusual” MREs, we demonstrate that CDS-targeted miRNAs require extensive base pairings in the 3’ side rather than the 5’ seed; cause gene silencing in an Argonaute-dependent, but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences for miRNAs to target CDS versus 3’UTR and suggest that CDS-targeted miRNAs may enlist a translational quality control (QC)-related mechanism to regulate translation in mammalian cells.