DTD (D-Tyr-tRNATyr deacylase) is known to be able to deacylate D-aminoacyl-tRNAs into free D-amino acids and tRNAs and therefore contributes to cellular resistance against D-amino acids in Escherichia coli and yeast. We have found that h-DTD (human DTD) is enriched in the nuclear envelope region of mammalian cells. Treatment of HeLa cells with D-Tyr resulted in nuclear accumulation of tRNATyr. D-Tyr treatment and h-DTD silencing caused tRNATyr downregulation. Furthermore, inhibition of protein synthesis by D-Tyr treatment and h-DTD silencing were also observed. D-Tyr, D-Asp and D-Ser treatment inhibited mammalian cell viability in a dose-dependent manner; overexpression of h-DTD decreased the inhibition rate, while h-DTD-silenced cells became more sensitive to the D-amino acid treatment. Our results suggest that h-DTD may play an important role in cellular resistance against D-amino acids by deacylating D-aminoacyl tRNAs at the nuclear pore. We have also found that m-DTD (mouse DTD) is specifically enriched in central nervous system neurons, its nuclear envelope localization indicates that D-aminoacyl-tRNA editing may be vital for the survival of neurons under high concentration of D-amino acids.

Tweetable abstract As an RNA virus, the fast evolution of SARS-CoV-2 is driven by the extensive RNA deamination by the host cells.

Aim:The inference of coronavirus evolution is largely based on mutations in SARS-CoV-2 genome. Misinterpretation of these mutations would mislead people about the evolution of SARS-CoV-2.Materials & methods:With 4521 lines of SARS-CoV-2, we obtained 3169 unique point mutation sites. We counted the numbers and calculated the minor allele frequency (MAF) of each mutation type.Results:Nearly half of the point mutations are C-T mismatches and 20% are A-G mismatches. The MAF of C-T and A-G mismatches is significantly higher than MAF of other mutation types.Conclusion:The excessive C-T mismatches do not resemble the random mutation profile. They are likely to be caused by the cytosine-to-uridine deamination system in hosts.

Study Purpose Malignant central airway obstruction (CAO) in non-small cell lung cancer (NSCLC) is associated with high morbidity and requires endobronchial palliative treatment to re-establish a free air passage. We investigate intratumoral therapy combining anti-angiogenic and cytotoxic as a feasible therapeutic modality to treat malignant CAO. Study Design Ten NSCLC subjects with symptomatic malignant CAO underwent endobronchial intratumoral cisplatin and Endostar co-injection after tumour debulking next to systemic cisplatin-based chemotherapy. Injection was performed immediately after debulking surgery and was then carried out on day 2, day 6 and day 10 past systemic chemotherapy. Nine subjects of control group constantly received traditional cisplatin-based chemotherapy. Bronchoscopy, CT scanning, histology, FEV1/FVC ratio, Karnofsky performance (KPS) and shortness of breath scores were analysed to assess therapeutic efficacy. Results All 10 subjects benefited from the intratumoral cisplatin and endostar co-injection and systemic chemotherapy combination therapy. Bronchoscopy and CT scanning analyses showed a massive airway widening after treatment. Increased KPS and reduced shortness of breath score were also observed. A substantial improvement of lung function was further confirmed by increased FEV1/FVC ratio. For subjects of control group, the improvement was moderate and obviously not as optimal as the 10 subjects with intratumoral injection. Conclusions We have shown that the intratumoral injection of cytotoxic cisplatin plus anti-angiogenic Endostar is an effective and safe adjuvant therapeutic option to treat malignant CAO in clinical practice. This time-staggered local and systemic treatment combination improves quality of life and clinical parameters, thus may provide a feasible therapeutic option for symptomatic CAO.