N7-methylguanosine regulatory genes well represented by METTL1 define vastly different prognostic, immune and therapy landscapes in adrenocortical carcinoma.

Although N7-methylguanosine (m7G) is one of the most frequent RNA modifications, it has received little attention. Adrenocortical carcinoma (ACC) is a highly malignant and easily metastatic tumor, eagerly needing for novel therapeutic strategy. Herein, a novel m7G risk signature (METTL1, NCBP1, NUDT1 and NUDT5) was constructed using the Lasso regression analysis. It possessed highly prognostic value and could improve the predictive accuracy and clinical making-decision benefit of traditional prognostic model. Its prognostic value was also successfully validated in GSE19750 cohort. Through CIBERSORT, ESTIMATE, ssGSEA and GSEA analyzes, high-m7G risk score was found to be closely associated with increased enrichment of glycolysis and suppression of anti-cancer immune response. Therapeutic correlation of m7G risk signature was also investigated using tumor mutation burden, the expressions of immune checkpoints, TIDE score, IMvigor 210 cohort and TCGA cohort. m7G risk score was a potential biomarker for predicting the efficacy of ICBs and mitotane. Furthermore, we explored the biofunctions of METTL1 in ACC cells through a series of experimentations. Overexpression of METTL1 stimulated the proliferation, migration and invasion of H295R and SW13 cells. Immunofluorescence assays revealed that the infiltrating levels of CD8+ T cells was lower and that of macrophages was higher in clinical ACC samples with high METTL1 expression compared to that in low expression ones. Silencing METTL1 could significantly inhibited tumor growth in mouse xenograft model. Western blot assays showed that METTL1 positively regulated the expression of glycolysis rate-limiting enzyme HK1. Finally, miR-885-5p and CEBPB were predicted as the upstream regulators of METTL1 through data mining of the public databases. In conclusions, m7G regulatory genes well represented by METTL1 profoundly affected the prognosis, tumor immune, therapeutic outcomes, and malignant progression of ACC.

GABAergic retinal ganglion cells regulate innate defensive responses.

Gamma-aminobutyric acid (GABA) is regarded as the most important inhibitory neurotransmitter in the central nervous system, including the retina. However, the roles of GABA-immunolabeled retinal ganglion cells (RGCs) have not been explored. Here, we report the expression of GABAergic RGCs that project to many brain areas in mice, including the superior colliculus. Selective ablation of the superior colliculus-projecting GABAergic RGCs, leaving other GABAergic RGCs intact, reduces the looming stimulus-induced defensive response without affecting image-forming functions; it also significantly enhances glucose metabolism in the superior colliculus, as determined by [18F]-fluorodeoxyglucose PET (FDG PET). Our findings demonstrate that superior colliculus-projecting GABAergic RGCs control the visually active defensive response by regulating superior colliculus neurons.

COVID-2019 Associated with Acquired Monocular Blindness.

OBJECTIVE: We documented an older female with Coronavirus(CoV) Disease 2019 (COVID-19) and concomitant acquired monocular blindness. We examined this phenomenon in order to understand COVID-19 better. METHODS: We observed an older female with COVID-19 and concomitant acquired monocular blindness. The following indicators were monitored during the course of the disease: ocular examinations, flash visual evoked potential examination, a blood test for COVID-19 IgM antibodies, as well as nasopharyngeal swab and tear sample tests for COVID-19 nucleic acid. RESULTS: The patient's visual acuity for the left eye was NLP and the intraocular pressure was 51 mmHg. Keratic precipitates similar to mutton-fat were spread over the corneal endothelium of the left eye. The funduscopic examination of the patient's left eye revealed severe retinal arterial ischemia, and the color of the retina was off-white. Compared to the right eye, the flash visual evoked potential examination revealed a moderate decrease in P2 wave amplitude for the left eye. A blood test was positive for COVID-19 IgM antibodies, and a nasopharyngeal swab test taken for COVID-19 nucleic acid was positive on May 4, 2020. A sample of the patient's tears was taken, and the nucleic acid test for COVID-19 was still positive two weeks later. CONCLUSIONS: Our study was the first to find that acute viral retinitis could occur in patients with COVID-19 and severe blindness could be associated with SARS-CoV-2 infection. Therefore, physicians should consider the possibility of coronavirus infection in patients with an abnormal fundus or suddenly vision loss.

Sox2 knockdown in the neonatal retina causes cell fate to switch from amacrine to bipolar.

Transcription factor Sox2 is widely recognized for its critical roles in the nervous system, including the neural retina. Here, we aimed to reveal the function of Sox2 in the process of mouse postnatal development. After the suppression of Sox2 at P0, there was an increase number in bipolar cells but a decrease in amacrine cells. Inhibited Sox2 expression also led to decreased visual function. Furthermore, we found a distinctive type of retinal cells expressing the characteristic proteins of both bipolar cells and amacrine cells at P6, which may be an intermediate state in which amacrine cells were transforming into bipolar cells. Transcription factors associated with the development of bipolar cells and amacrine cells also support those changes. Our work indicated that inhibition of Sox2 could change cell fate by affecting transcription factors in the development of bipolar cells and amacrine cells, may provide new directions for the study and treatment of retinal genetic diseases and retinal dysplasia.