improved 24 . Nanopore sequencing methods were designed to directly detect RNA modifications based on base-calling errors, which are bioinformatically demanding and highly sensitive to the abundance of the transcripts as well as modification levels. Hence, a quantitative, accurate and sensitive method for global Ψ detection is urgently needed.

Enantioselective total syntheses of (−)-grayanotoxin III, (+)-principinol E, and (−)-rhodomollein XX were accomplished based on a convergent strategy. The left- and right-wing fragments were assembled via the diastereoselective Mukaiyama aldol reaction catalyzed by a chiral hydrogen bond donor. The unique 7-endo-trig cyclization based on a bridgehead carbocation forged the 5/7/6/5 tetracyclic skeleton that underwent redox manipulations and 1,2-migration to access different grayanane diterpenoids.

BackgroundThe pathogenesis of empty nose syndrome (ENS) has not been elucidated so far. Though postulated, there remains a lack of experimental evidence about the roles of nasal aerodynamics on the development of ENS. ObjectiveTo investigate the nasal aerodynamic features of ENS andto explore the role of aerodynamic changes on the pathogenesis of ENS.MethodsSeven sinonasal models were numerically constructed, based on the high resolution computed tomography images of seven healthy male adults. Bilateral radical inferior/middle turbinectomy were numerically performed to mimic the typical nasal structures of ENS-inferior turbinate (ENS-IT) and ENS-middle turbinate (ENS-MT). A steady laminar model was applied in calculation. Velocity, pressure, streamlines, air flux and wall shear stress were numerically investigated. Each parameter of normal structures was compared with those of the corresponding pathological models of ENS-IT and ENS-MT, respectively. ResultsENS-MT: Streamlines, air flux distribution, and wall shear stress distribution were generally similar to those of the normal structures; nasal resistances decreased. Velocities decreased locally, while increased around the sphenopalatine ganglion by 0.20±0.17m/s and 0.22±0.10m/s during inspiration and expiration, respectively. ENS-IT: Streamlines were less organized with new vortexes shown near the bottom wall. The airflow rates passing through the nasal olfactory area decreased by 26.27%±8.68% and 13.18%±7.59% during inspiration and expiration, respectively. Wall shear stresses, nasal resistances and local velocities all decreased. ConclusionOur CFD simulation study suggests that the changes in nasal aerodynamics may play an essential role in the pathogenesis of ENS. An increased velocity around the sphenopalatine ganglion in the ENS-MT models could be responsible for headache in patients with ENS-MT. However, these results need to be validated in further studies with a larger sample size and more complicated calculating models.

Pseudouridine (ψ) is an abundant post-transcriptional RNA modification in ncRNA and mRNA. However, transcriptome-wide measurement of individual ψ sites remains unaddressed. Here, we develop "PRAISE", via selective chemical labeling of ψ by bisulfite to induce nucleotide deletion signature during reverse transcription, to realize quantitative assessment of the ψ landscape in the human transcriptome. Unlike traditional RNA/DNA bisulfite treatment, our approach is based on quaternary base mapping and revealed a ~10% median modification level for 2,714 confident ψ sites in HEK293T cells. By perturbing pseudouridine synthases, we obtained differential mRNA targets of PUS1, PUS7 and TRUB1, with TRUB1 mRNA targets showing the highest modification stoichiometry. In addition, we identified and quantified known and novel ψ sites in mitochondrial mRNA, catalyzed by a mitochondria-localized isoform of PUS1. Collectively, we provide a sensitive and convenient method to measure transcriptome-wide ψ ; we envision this quantitative approach would facilitate emerging efforts to elucidate the function and mechanism of mRNA pseudouridylation.