A Direct Chemical Repair of Etheno-Type RNA Damages.

Etheno damages in RNA represent a unique class of structural alterations that arise from exposure to various environmental stressors or endogenous processes. They significantly distort the RNA structure and affect crucial biological functions, including RNA-protein interactions, ribosome function, and translation fidelity. However, repair mechanisms for those etheno damages in RNA are still being elucidated.

Prevalence and prognostic value of PD-L1 expression and tumor mutational burden in persistent, recurrent, or metastatic cervical cancer.

Objective: To evaluate the prevalence and prognostic role of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in patients with non-immunotherapy-treated advanced cervical cancer.

Methods: Clinical data were retrospectively collected from medical records between January 1, 2008, and December 31, 2016, at Asan Medical Center (Korea); archived tumor samples were assessed for PD-L1 expression (combined positive score [CPS] ≥1) and TMB (≥175 mutations/exome). Overall survival (OS) was defined as time from advanced diagnosis or initiation of first-line or second-line systemic therapy until death/last follow-up.

Selective Methylation of Nucleosides via an Generated Methyl Oxonium.

A very mild and efficient procedure has been developed for the preparation of -methylated uridine, pseudouridine, guanosine and inosine derivatives. This process was compatible with free hydroxyls within the ribose and did not require precautions on the protection or deprotection of other functionalities. The key to this extremely mild methylation without protection relied on the generated methyl oxonium from the Wittig reagent and methanol.

Photo-Facilitated Detection and Sequencing of 5-Formylcytidine RNA.

5-Formylcytidine (f C) is one of the epigenetic nucleotides in tRNA. Despite the evident importance of f C in gene expression regulation, little is known about its exact amount and position. To capture this information, we developed a modification-specific functionalization with a semi-stabilized ylide.

A Light-Controllable Chemical Modulation of m A RNA Methylation.

Bioactive small molecules with photo-removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo-activatable small-molecule methyltransferase agonist. By blocking the functional N-H group on MPCH with a photo-removable ortho-nitrobenzyl moiety, we have developed a promising photo-caged compound that had completely concealed its biological activity.

A NaI/HO-Mediated Sulfenylation and Selenylation of Unprotected Uracil and Its Derivatives.

An efficient iodide-catalyzed/hydrogen peroxide mediated sulfenylation and selenylation of unprotected uracil and its derivatives with simple thiols and diselenides was established. This coupling tolerates a broad variety of functional groups to provide diverse 5-sulfur/selenium-substituted uracil derivatives in good to excellent yields (up to 93%).

Iodide/H₂O₂ Catalyzed Intramolecular Oxidative Amination for the Synthesis of 3,2'-Pyrrolidinyl Spirooxindoles.

An ammonium iodide/hydrogen peroxide-mediated intramolecular oxidative amination of 3-aminoalkyl-2-oxindoles was achieved, affording the corresponding 3,2'-pyrrolidinyl spirooxindoles and their 6- or 7-membered analogous in moderate to high yields. This metal-free procedure features very mild reaction conditions, non-toxicity and easily handled hydrogen peroxide as a clean oxidant.

Ruthenium-Catalyzed Decarboxylative C-H Alkenylation in Aqueous Media: Synthesis of Tetrahydropyridoindoles.

We disclose herein a Ru(II)-catalyzed decarboxylative and oxidative coupling of N-substituted indolyl carboxylic acids with broad substrate scope in an aqueous solution. This method provides a sustainable and efficient access to synthesize various indole-fused cyclohexanyl acetic acids under mild conditions.