M⁵C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m⁵C maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using Drosophila as a model, we reveal that embryos lacking maternal mRNA m⁵C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m⁵C. From invertebrates to the lineage leading to humans, two waves of m⁵C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m⁵C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m⁵C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m⁵C in biology and disease.

A novel biomimetic bone scaffold was successfully prepared in this study, which was composed of calcium sulfate hemihydrate (CSH), collagen and nano-hydroxyapatite (nHAC). CSH/nHAC was prepared and observed with scanning electron microscope and rhBMP-2 was introduced into CSH/nHAC. The released protein content from the scaffold was detected using high performance liquid chromatography at predetermined time interval. In vivo bone formation capacity was investigated by means of implanting the scaffolds with rhBMP-2 or without rhBMP-2 respectively into a critical size defect model in the femoral condyle of rabbit. The releasing character of rhBMP-2 was that an initial burst release (37.5%) was observed in the first day, followed by a sustained release and reached 100% at the end of day 20. The CSH/nHAC showed a gradual decrease in degradation with the content of nHAC increase. The results of X-rays, Micro CT and histological observation indicated that more new bone was formed in rhBMP-2 group. The results implied that this new injectable bone scaffold should be very promising for bone repair and has a great potential in bone tissue engineering.

Advances in sequencing technologies have empowered epitranscriptomic profiling at the single-base resolution. Putative RNA modification sites identified from a single high-throughput experiment may contain one type of modification deposited by different writers or different types of modifications, along with false positive results because of the challenge of distinguishing signals from noise. However, current tools are insufficient for subtyping, visualization, and denoising these signals. Here, we present iMVP, which is an interactive framework for epitranscriptomic analysis with a nonlinear dimension reduction technique and density-based partition. As exemplified by the analysis of mRNA m⁵C and ModTect variant data, we show that iMVP allows the identification of previously unknown RNA modification motifs and writers and the discovery of false positives that are undetectable by traditional methods. Using putative m⁶A/m⁶Am sites called from 8 profiling approaches, we illustrate that iMVP enables comprehensive comparison of different approaches and advances our understanding of the difference and pattern of true positives and artifacts in these methods. Finally, we demonstrate the ability of iMVP to analyze an extremely large human A-to-I editing dataset that was previously unmanageable. Our work provides a general framework for the visualization and interpretation of epitranscriptomic data.

N ⁶,2’-O-dimethyladenosine (m⁶Am) is a modified nucleotide located at the first transcribed position in mRNA and snRNA that is essential for diverse physiological processes. m⁶Am mapping methods assume each gene uses a single start nucleotide. However, gene transcription usually involves multiple start sites, generating numerous 5’ isoforms. Thus, gene-level annotations cannot capture the diversity of m⁶Am modification in the transcriptome. Here, we describe CROWN-seq, which simultaneously identifies transcription-start nucleotides and quantifies m⁶Am stoichiometry for each 5’ isoform that initiates with adenosine. Using CROWN-seq, we map the m⁶Am landscape in nine human cell lines. Our findings reveal that m⁶Am is nearly always a high stoichiometry modification, with only a small subset of cellular mRNAs showing lower m⁶Am stoichiometry. We find that m⁶Am is associated with increased transcript expression and provide evidence that m⁶Am may be linked to transcription initiation associated with specific promoter sequences and initiation mechanisms. These data suggest a potential new function for m⁶Am in influencing transcription.

Autonomous delivery of suspended payloads with MAVs has many applications in rescue and logistics transportation. Robust and online estimation of the payload status is important but challenging especially in outdoor environments. The paper develops a novel real-time system for estimating the payload position; the system consists of a monocular fisheye camera and a novel encoder-based device. A Gaussian fusion-based estimation algorithm is developed to obtain the payload state estimation. Based on the robust payload position estimation, a payload controller is presented to ensure the re-liable tracking performance on aggressive trajectories. Several experiments are performed to validate the high performance of the proposed method.