N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this reversible RNA modification can be interpreted by cytoplasmic and nuclear 'm6A reader' proteins to fine-tune gene expression, such as mRNA degradation and translation initiation. Here we profiled transcriptome-wide m6A sites in adult mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic modification in brain. Interestingly, the mRNA targets of fragile X mental retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A marks. Loss of functional FMRP leads to Fragile X syndrome (FXS), the most common inherited form of intellectual disability. Transcriptome-wide gene expression profiling identified 2035 genes differentially expressed in the absence of FMRP in cortex, and 92.5% of 174 downregulated FMRP targets are marked by m6A. Biochemical analyses indicate that FMRP binds to the m6A sites of its mRNA targets and interacts with m6A reader YTHDF2 in an RNA-independent manner. FMRP maintains the stability of its mRNA targets while YTHDF2 promotes the degradation of these mRNAs. These data together suggest that FMRP regulates the stability of its m6A-marked mRNA targets through YTHDF2, which could potentially contribute to the molecular pathogenesis of FXS.

Traumatic spinal cord injury (SCI) is caused by external physical impacts and can induce complex cascade events, sometimes converging to paralysis. Existing clinical drugs to traumatic SCI have limited therapeutic efficacy because of either the poor blood–spinal cord barrier (BSCB) permeability or a single function. Here, we suggest a “pleiotropic messenger” strategy based on near-infrared (NIR)–triggered on-demand NO release at the lesion area for traumatic SCI recovery via the concurrent neuroregeneration and neuroprotection processing. This NO delivery system was constructed as upconversion nanoparticle (UCNP) core coated by zeolitic imidazolate framework–8 (ZIF-8) with NO donor (CysNO). This combined strategy substantial promotes the repair of SCI in vertebrates, ascribable to the pleiotropic effects of NO including the suppression of gliosis and inflammation, the promotion of neuroregeneration, and the protection of neurons from apoptosis, which opens intriguing perspectives not only in nerve repair but also in neurological research and tissue engineering.

Ticks are important vector hosts of pathogens which cause human and animal diseases worldwide. Diverse viruses have been discovered in ticks; however, little is known about the ecological factors that affect the tick virome composition and evolution. Herein, we employed RNA sequencing to study the virome diversity of the Haemaphysalis longicornis and Rhipicephalus microplus ticks sampled in Hubei Province in China. Twelve RNA viruses with complete genomes were identified, which belonged to six viral families: Flaviviridae, Matonaviridae, Peribunyaviridae, Nairoviridae, Phenuiviridae, and Rhabdoviridae. These viruses showed great diversity in their genome organization and evolution, four of which were proposed to be novel species. The virome diversity and abundance of R. microplus ticks fed on cattle were evidently high. Further ecological analyses suggested that host species and feeding status may be key factors affecting the tick virome structure. This study described a number of novel viral species and variants from ticks and, more importantly, provided insights into the ecological factors shaping the virome structures of ticks, although it clearly warrants further investigation.

SummaryChemical modifications to nucleobases have a great influence on various cellular processes, by making gene regulation more complex, thus indicating their profound impact on aspects of heredity, growth, and disease. Here, we provide the first genome-wide map of 5-formyluracil (5fU) in living tissues and evaluate the potential roles for 5fU in genomics. We show that an azido derivative of (2-benzimidazolyl)acetonitrile has high selectivity for enriching 5fU-containing genomic DNA. The results have demonstrated the feasibility of using this method to determine the genome-wide distribution of 5fU. Intriguingly, most 5fU sites were found in intergenic regions and introns. Also, distribution of 5fU in human thyroid carcinoma tissues is positively correlated with binding sites of POLR2A protein, which indicates that 5fU may distributed around POLR2A-binding sites.

5-Formylcytosine (5fC) is known as one of the key players in the process of active DNA demethylation and displays essential epigenetic functions in mammals.

Human granulocyte-macrophage colony stimulating factor (hGM-CSF) is used clinically to treat leucopenia typically caused by cancer chemotherapy or radiotherapy. This study used multiple strategies to obtain very high expression levels of OsrhGM-CSF (14 microg/seed) in rice endosperm. Electron micrographs of immunogold-labeled transgenic endosperm showed that rhGM-CSF was not only localized in protein bodies but was also distributed in the apoplast. A biological activity assay indicated that OsrhGM-CSF stimulated the growth of TF-1 cells in vitro. In addition, the transgene was used to effectively treat leucopenia by oral administration of the unprocessed transgenic grains. In cyclophosphamide-induced leucopenic mice, transgenic seeds produced a 27% (t=0.021) gain in leukocytes after 14 days feeding. Even in non-leucopenic mice, leukocyte gain was 37% (t=0.002) more than that of mice fed non-transgenic seeds. This study provides a novel approach to the use of oral unprocessed transgenic OsrhGM-CSF seeds to treat leucopenia.

Indocyanine green-platinum porphyrins integrated conjugated polymer hybrid nanoparticles for bimodal photothermal and two-photon photodynamic therapy with near-infrared irradiation.

Simultaneous fluorogenic switch-on detection and single-base resolution analysis of 5fC through yielding an intramolecular cyclization nucleobase has been presented.