DNA and histone modifications exhibit noticeable impacts on gene expression 1 . Being the most prevalent internal modification in mRNA, N 6 -Methyladenosine (m 6 A) mRNA modification emerges as an important post-transcriptional mechanism of gene regulation 2 - 4 and plays critical roles in various normal and pathological bioprocesses 5 - 12 . However, how m 6 A is precisely and dynamically deposited in the transcriptome remains elusive. Here we report that H3K36me3 histone modification, a marker for transcription elongation, globally guides m 6 A modification. We found that m 6 A modifications enrich in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a critical component of the m 6 A methyltransferase complex (MTC), which in turn facilitates the binding of the m 6 A MTC to adjacent RNA polymerase II, and thereby delivering the m 6 A MTC to actively transcribed nascent RNAs to deposit m 6 A co-transcriptionally. In mouse embryonic stem cells, phenocopying Mettl14 silencing, H3K36me3 depletion also induces m 6 A reduction transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the critical roles of H3K36me3 and METTL14 in determining precise and dynamic m 6 A deposition in mRNA, and uncover another layer of gene expression regulation involving crosstalk between histone modification and RNA methylation.

Highlights d Development of two potent FTO inhibitors with IC 50 values in the low nanomolar range d KD of FTO or pharmacological inhibition of FTO suppresses LSC/LIC self-renewal d Targeting FTO suppresses immune checkpoint gene expression and immune evasion d Targeting FTO by potent inhibitors holds therapeutic promise against various cancers

As the most promising lead‐free one, tin‐halides based perovskite solar cells still suffer from the severe bulk‐defect due to the easy oxidation of tin from divalent to tetravalent. Here, a general and effective strategy is delivered to modulate the microstructure of 2D/3D heterogeneous tin‐perovskite absorber films by substituting FAI with FPEABr in FASnI3. The introduction of 2D phase can induce highly oriented growth of 3D FASnI3 and it is revealed in the optimal 2D/3D film that 2D phase embraces 3D grains and locates at the surfaces and grain boundaries. The FPEA+ based 2D tin‐perovskite capping layer can offer a reducing atmosphere for vulnerable 3D FASnI3 grains. The unique microstructure effectively suppresses the well‐known oxidation from Sn2+ to Sn4+, as well as decreasing defect density, which leads to a remarkable enhanced device performance from 9.38% to 14.81% in conversion efficiency. The certified conversion efficiency of 14.03% announces a new record and moves a remarkable step from the last one (12.4%). Besides of this breakthrough, this work definitely paves a new way to fabricate high‐quality tin‐perovskite absorber film by constructing effective 2D/3D microstructures.

The outbreak of 2019 coronavirus disease has been a challenge for hospital laboratories because of the huge number of samples that must be tested for the presence of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simple and rapid immunodiagnostic methods are urgently needed to identify positive cases. Here we report the development of a rapid and sensitive lateral flow immunoassay (LFIA) that uses lanthanide-doped polysterene nanoparticles (LNPs) to detect anti-SARV-CoV-2 IgG in human serum. A recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed onto a nitrocellulose membrane to capture specific IgG. Mouse anti-human IgG antibody was labeled with self-assembled LNPs that served as a fluorescent reporter. A 100-μL aliquot of serum samples (1:1000 dilution) was used for this assay and the whole detection process took 10 min. The results of the validation experiment met the requirements for clinical diagnostic reagents. A value of 0.0666 was defined as the cutoff value by assaying 51 normal samples. We tested 7 samples that were positive by reversetranscription (RT-)PCR and 12 that were negative but clinically suspicious for the presence of anti-SARS-CoV-2 IgG. One of the negative samples was determined to be SARS-CoV-2 IgG positive, while the results for the other samples were consistent with those obtained by RT-PCR. Thus, this assay can achieve rapid and sensitive detection of anti-SARS-CoV-2 IgG in human serum and allow positive identification in suspicious cases; it can also be useful for monitoring the progression COVID-19 and evaluating patients' response to treatment.

Emerging evidence showed that long non-coding RNAs (lncRNAs) play important roles in a wide range of biological processes and dysregulated lncRNAs are involved in many complex human diseases, including cancer. Although a few lncRNAs’ functions in cancer have been characterized, the detailed regulatory mechanisms of majority of lncRNAs in cancer initiation and progression remain largely unknown. In this review, we summarized recent progress on the mechanisms and functions of lncRNAs in cancer, especially focusing on the oncogenic and tumor suppressive roles of the newly identified lncRNAs, and the pathways these novel molecules might be involved in. Their potentials as biomarkers for diagnosis and prognosis in cancer are also discussed in this paper.