Journal
- MedComm Introduction
- Molecular Biomedicine Introduction
- Signal Transduction and Targeted Therapy Introduction
- MedComm | The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19
- MedComm | Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor
Editors-in-Chief：
Carlo M.Croce
Prof. Kang Zhang
Yu-quan Wei
Editors-in-Chief：
James H.Naisimth
Günter P. Wagner
Yu-quan Wei
Editors-in-Chief：
Arnold J.M.Driessen
Yu-quan Wei
Editors-in-Chief：
Robin Ali
Michael Karin
Kang Zhang
Editors-in-Chief：
Mohan Edirisinghe
Zhiyong Qian
Editors-in-Chief：
Guido Kroemer
Yong Peng
Journal
- MedComm Introduction
- Molecular Biomedicine Introduction
- Signal Transduction and Targeted Therapy Introduction
- MedComm | The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19
- MedComm | Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor
Editors-in-Chief：
Carlo M.Croce
Prof. Kang Zhang
Yu-quan Wei
Editors-in-Chief：
James H.Naisimth
Günter P. Wagner
Yu-quan Wei
Editors-in-Chief：
Arnold J.M.Driessen
Yu-quan Wei
Editors-in-Chief：
Robin Ali
Michael Karin
Kang Zhang
Editors-in-Chief：
Mohan Edirisinghe
Zhiyong Qian
Editors-in-Chief：
Guido Kroemer
Yong Peng
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for versatile diagnostic assays that can discriminate among emerging variants of the virus. Here we report the development and performance benchmarking of an inexpensive (approximately US$0.30 per test) assay for the rapid (sample-to-answer time within 30 min) colorimetric detection of SARS-CoV-2 variants. The assay, which we integrated into foldable paper strips, leverages nucleic acid strand-displacement reactions, the thermodynamic energy penalty associated with single-base-pair mismatches and the metal-ion-controlled enzymatic cleavage of urea to amplify the recognition of viral RNAs for the colorimetric readout of changes in pH via a smartphone. For 50 throat swab samples, the assay simultaneously detected the presence of SARS-CoV-2 and mutations specific to the SARS-CoV-2 variants Alpha, Beta and Gamma, with 100% concordance with real-time quantitative polymerase chain reaction and RNA sequencing. Customizable and inexpensive paper-based assays for the detection of viruses and their variants may facilitate viral surveillance.
2022-07-14
Nature Biomedical Engineering
West China Hospital, Sichuan University
Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. To understand the molecular mechanisms underlying SCLC metastasis, we generated SCLC mouse models with orthotopically transplanted genome-edited lung organoids and performed multiomics analyses. We found that a deficiency of KMT2C, a histone H3 lysine 4 methyltransferase frequently mutated in extensive-stage SCLC, promoted multiple-organ metastases in mice. Metastatic and KMT2C-deficient SCLC displayed both histone and DNA hypomethylation. Mechanistically, KMT2C directly regulated the expression of DNMT3A, a de novo DNA methyltransferase, through histone methylation. Forced DNMT3A expression restrained metastasis of KMT2C-deficient SCLC through repressing metastasis-promoting MEIS/HOX genes. Further, S-(5′-adenosyl)-L-methionine, the common cofactor of histone and DNA methyltransferases, inhibited SCLC metastasis. Thus, our study revealed a concerted epigenetic reprogramming of KMT2C- and DNMT3A-mediated histone and DNA hypomethylation underlying SCLC metastasis, which suggested a potential epigenetic therapeutic vulnerability.
2022-04-21
Nature Cancer
West China Hospital, Sichuan University
