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TRMT1 is an N2-methylguanosine (m2G) and N2,N2-methylguanosine (m22G) methyltransferase that targets G26 of both cytoplasmic and mitochondrial tRNAs. In higher eukaryotes, most cytoplasmic tRNAs with G26 carry m22G26, although the majority of mitochondrial G26-containing tRNAs carry m2G26 or G26, suggesting differences in the mechanisms by which TRMT1 catalyzes modification of these tRNAs. Loss-of-function mutations of human TRMT1 result in neurological disorders and completely abrogate tRNA:m22G26 formation. However, the mechanism underlying the independent catalytic activity of human TRMT1 and identity of its specific substrate remain elusive, hindering a comprehensive understanding of the pathogenesis of neurological disorders caused by TRMT1 mutations. Here, we showed that human TRMT1 independently catalyzes formation of the tRNA:m2G26 or m22G26 modification in a substrate-dependent manner, which explains the distinct distribution of m2G26 and m22G26 on cytoplasmic and mitochondrial tRNAs. For human TRMT1-mediated tRNA:m22G26 formation, the semi-conserved C11:G24 serves as the determinant, and the U10:A25 or G10:C25 base pair is also required, while the size of the variable loop has no effect. We defined the requirements of this recognition mechanism as the "m22G26 criteria". We found that the m22G26 modification occurred in almost all the higher eukaryotic tRNAs conforming to these criteria, suggesting the "m22G26 criteria" are applicable to other higher eukaryotic tRNAs. [ABSTRACT FROM AUTHOR]

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA‐binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA‐modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'‐O‐methylation of tRNAs, thus regulating translation in a manner depending on its tRNA‐modification activity. On the other hand, nucleus‐localized hTrmt13 directly binds DNA as a transcriptional co‐activator of key epithelial–mesenchymal transition factors, thereby promoting cell migration independent of tRNA‐modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA‐modifying enzyme provides a new perspective for understanding epitranscriptomic regulation. Synopsis: tRNA methyltransferases regulate translation through tRNA modification, while chromatin‐associated RBPs are thought to regulate transcription primarily though lncRNAs. Here, human tRNA methyltransferase hTrmt13 is found to have an unexpected additional nuclear function in regulating transcription. Cytoplasmic hTrmt13 regulates protein translation dependent on its tRNA 2'‐O‐methylation activity.Nuclear hTrmt13 directly binds DNA to promote transcription, independent of its catalytic activity.Nuclear hTrmt13 promotes cell migration and cancer metastasis by acting as a transcriptional co‐activator. [ABSTRACT FROM AUTHOR]

The weak fluorescence (quantum yield <1 % in cyclohexane) of phenothiazine (PTZ) impedes its further application. In addition, the nitro group (NO2) is a well‐known fluorescence quencher. Interestingly, we obtained a highly fluorescent chromophore by combining these two moieties, forming 3‐nitrophenothiazine (PTZ‐NO2). For comparison, a series of PTZ derivatives bearing electron‐withdrawing groups (EWGs; CN and CHO) or electron‐donating groups (EDGs; OMe) at the 3‐position have been designed and synthesized. The phenothiazines bearing EWGs exhibited enhanced emission compared with the parent PTZ or EDG derivatives. Computational approaches unveiled that for PTZ and PTZ‐OMe, the transitions are from HOMOs dominated by π orbitals to LUMOs of mixed sulfur nonbonding–π* orbitals, and hence are partially forbidden. In contrast, the EWGs lower the energy level of the lone‐pair electrons on the sulfur atom, thereby suppressing the mixing of the nonbonding orbital with the π* orbital in the LUMO, such that the allowed ππ* transition becomes dominant. This work thus demonstrates a judicious chemical design to fine‐tune the transition character in PTZ analogues, with PTZ‐NO2 attaining 100 % emission quantum yields in nonpolar solvent. [ABSTRACT FROM AUTHOR]

The weak fluorescence (quantum yield <1 % in cyclohexane) of phenothiazine (PTZ) impedes its further application. In addition, the nitro group (NO 2 ) is a well-known fluorescence quencher. Interestingly, we obtained a highly fluorescent chromophore by combining these two moieties, forming 3-nitrophenothiazine (PTZ-NO 2 ). For comparison, a series of PTZ derivatives bearing electron-withdrawing groups (EWGs; CN and CHO) or electron-donating groups (EDGs; OMe) at the 3-position have been designed and synthesized. The phenothiazines bearing EWGs exhibited enhanced emission compared with the parent PTZ or EDG derivatives. Computational approaches unveiled that for PTZ and PTZ-OMe, the transitions are from HOMOs dominated by π orbitals to LUMOs of mixed sulfur nonbonding-π* orbitals, and hence are partially forbidden. In contrast, the EWGs lower the energy level of the lone-pair electrons on the sulfur atom, thereby suppressing the mixing of the nonbonding orbital with the π* orbital in the LUMO, such that the allowed ππ* transition becomes dominant. This work thus demonstrates a judicious chemical design to fine-tune the transition character in PTZ analogues, with PTZ-NO 2 attaining 100 % emission quantum yields in nonpolar solvent., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: We report a case of an 18-year-old woman with systemic antibiotic anaphylaxis who presented anasarca and bilateral visual loss two weeks after the intravenous use of pazufloxacin. Ancillary fundus tests revealed bilateral cotton-wool spots, Purtscher flecken, edema, and retinal arteriolar occlusion around the optic disc. After pulse corticosteroid, administration of anti-anaphylactic agent, and general support therapy for one month, the patient showed a favorable change, with the symptoms lessened or free systemically, except the continuous aggravation of fundus ischemic change. After two intravitreal injections of Ranibizumab, there were still a large area of capillary non-perfusion and neovacularizations in the binocular retina, resulting in vitreous hemorrhage. The patient's visual acuity had still light perception after right-eye vitrectomy and presented no improvement during the postoperative follow-up of two years. Literature review revealed that there were many causes associated with Purtscher-like retinopathy, and the consequent visual impairment varied significantly. Prompt management of the underlying condition is crucial in giving the patient the best chance to restore vision.

Objective: To study the protective effects of polysaccharide of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic rats., Method: With the doses of polysaccharide of Spirulina platensis (PSP) and Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by i.g. administration to alloxan induced diabetic rats respectively for 6 weeks. Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The contraction and relaxation response to NE and ACh in aortic rings of the alloxan induced diabetic rats has been studied., Result: The results showed the compound of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum and increase HDL-C than in the alloxan induced diabetic rats. The contraction responses to NE in aortic rings of the alloxan induced diabetic rats were significantly elevated in the normal rats, and the responses to ACh were significantly lower. PSP and PST compound could significantly lower the responses to NE and significantly elevate the responses to ACh in aortic rings of the alloxan induced diabetic rats., Conclusion: PSP and PST compound could decrease blood glucose and could protect the vascular of alloxan induced diabetic rats.