METTL3-mediated m^(6)A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition

Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithelial-mesenchymal transition(EMT)contribute to the fibrosis formation.N^(6)-Methyladenosine(m^(6)A)modification has been implicated in the EMT process and multiple fibrotic diseases.The role of m^(6)A modification in EMT-related subretinal fibrosis has not yet been elucidated.In this study,we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization,METTL3 was upregulated in RPE cells.Through m^(6)A epitranscriptomic microarray and further verification,high-mobility group AT-hook 2(HMGA2)was identified as thekey downstream target of METTL3,subsequently activating potent EMT-inducing transcription factor SNAIL.Finally,by subretinal injections of adeno-associated virus vectors,we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo.In conclusion,our present research identified an epigenetic mechanism of METTL3-m^(6)A-HMGA2 in subretinal fibrosis and EMT of RPE cells,providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.

A tunable genome editing system of the prime editor mediated by dihydrofolate reductase

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(CRISPR/Cas)system was discovered in bacteria and archaea as an adaptive immunity system to protect against exogenous DNA(Barrangou et al.,2007).This system has been developed into a powerful gene editing tool for eukaryotic genome manipulation that has therapeutic opportunities against hereditary diseases(Cong et al.,2013),especially monogenic diseases.

The intestinal microbiome of an Indo-Pacific humpback dolphin(Sousa chinensis)stranded near the Pearl River Estuary,China

The mammalian intestinal microbiome is critical for host health and disease resistance.However,the cetacean intestinal microbiota remains relatively unexplored.By using high-throughput 16S rRNA gene sequencing,we analyzed intestinal bacterial samples from an Indo-pacific humpback dolphin(Sousa chinensis)stranded near the Pearl River Estuary in China.The samples included 3 anatomical regions(foregut,midgut,and rectum)and 2 anatomical locations(content and mucus).Our analyses revealed that the dolphin intestinal bacteria contained 139 operational taxonomic units(OTUs),dominated at the phyla level by Firmicutes(47.05%in the content;94.77%in the mucus),followed by Bacteroidetes(23.63%in the content;1.58%in the mucus)and Gammaproteobacteria(14.82%in the content;2.05%in the mucus).The intestinal bacteria had a small core community(15 OTUs,accounting for 99.74%of the reads),some of which could be potentially pathogenic to both human and dolphins.As an alternative to sampling the dolphin intestinal bacteria,fecal sampling could be used.Additionally,function potentials such as,xenobiotics biodegradation,beta-lactam resistance,and human disease-related pathways,were detected in the dolphin intestinal bacteria.These findings provide the first baseline knowledge of the intestinal microbiome of the Indo-Pacific humpback dolphin,which may offer new insights into cetacean conservation by using microbial surveillance.

Record of a juvenile Omura's whale live stranded in Hainan Island:Evidence of a potential breeding ground in the South China Sea?

On January 12,2011,a very young juvenile Bryde's-like baleen whale was found stranded alive on the east coast of Hainan Island,in the South China Sea.Unfortunately,it died the next morning.This baleen whale showed some unique external morphology and skull features of the Omura's whale(Balaenoptera omurai).Subsequently,it was genetically identified as an Omura's whale using two different mitochondrial DNA markers.This study documents the first confirmed live stranding of a juvenile Omura's whale on Hainan Island,China.Our findings expand the known distribution range of this species in Chinese waters and may indicate that waters around Hainan Island in the South China Sea could be a potential breeding ground for the Omura's whale.