Loss of the m6A methyltransferase METTL3 in monocyte-derived macrophages ameliorates Alzheimer's disease pathology in mice.

Alzheimer's disease (AD) is a heterogeneous disease with complex clinicopathological characteristics. To date, the role of m6A RNA methylation in monocyte-derived macrophages involved in the progression of AD is unknown. In our study, we found that methyltransferase-like 3 (METTL3) deficiency in monocyte-derived macrophages improved cognitive function in an amyloid beta (Aβ)-induced AD mouse model. The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A (Dnmt3a) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of alpha-tubulin acetyltransferase 1 (Atat1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of α-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Aβ clearance, which led to the alleviated symptoms of AD. Collectively, our findings demonstrate that m6A methylation could be a promising target for the treatment of AD in the future

Shanghai Pulmonary Hospital Experts Consensus on the Management of Ground-Glass Nodules Suspected as Lung Adenocarcinoma (Version 1)

Background and objective As computed tomography (CT) screening for lung cancer becomes more common in China, so too does detection of pulmonary ground-glass nodules (GGNs). Although anumber of national or international guidelines about pulmonary GGNs have been published,most of these guidelines are produced by respiratory, oncology or radiology physicians, who might not fully understand the progress of modern minimal invasive thoracic surgery, and these current guidelines may overlook or underestimate the value of thoracic surgery in the management of pulmonary GGNs. In addition, the management for pre-invasive adenocarcinoma is still controversial. Based onthe available literature and experience from Shanghai Pulmonary Hospital, we composed this consensus about diagnosis and treatment of pulmonary GGNs. For lesions which are considered as adenocarcinoma in situ, chest thin layer CT scan follow-up is recommended and resection can only be adopt in some specific cases and excision should not exceed single segment resection. For lesions which are considered as minimal invasive adenocarcinoma, limited pulmonary resection or lobectomy is recommended. For lesions which are considered as early stage invasive adenocarcinoma, pulmonary resection is recommend and optimal surgical methods depend on whether ground glass component exist, location, volume and number of the lesions and physical status of patients. Principle of management of multiple pulmonary nodules is that primary lesions should be handled with priority, with secondary lesions taking into account