68-2.64) compared with no RBV/IFN-α therapy. The propensity score-matched cohort and subgroup analysis displayed similar results. RBV/IFN-α therapy was not observed to improve clinical outcomes in COVID-19 patients suggesting that RBV/IFN-α therapy should be avoided in COVID-19 treatment.RBV/IFN-α therapy was not observed to improve clinical outcomes in COVID-19 patients suggesting that RBV/IFN-α therapy should be avoided in COVID-19 treatment. Several studies have investigated MRI breast cancer screening in women at increased risk, but little is known about their preferences. In this study, experiences, expectations and preferences for MRI and mammography were evaluated among women undergoing screening with MRI and/or mammography in the randomized FaMRIsc trial. A 17-item questionnaire was sent to 412 women in the FaMRIsc trial. Participants were aged 30-55 years, had a ≥20% cumulative lifetime risk, but no BRCA1/2 or TP53 gene variant, and were screened outside the population-based screening program. Women received annual mammography (mammography-group), or annual MRI and biennial mammography (MRI-group). We asked whether women trust the screening outcome, what they consider as (dis)advantages, which screening they prefer and what they expect of the early detection by the screening tools. 255 (62%) women completed our questionnaire. The high chance of early cancer detection was the most important advantage of MRI screening (MRI-group 95%; mammography-group 74%), while this was also the main advantage of mammography (MRI-group 57%; mammography-group 72%). Most important disadvantages of MRI were the small tunnel and the contrast fluid (for 23-36%), and of mammography were its painfulness and X-radiation (for 48-60%). Almost the whole MRI-group and half the mammography-group preferred screening with MRI (either alone or with mammography). Most women would prefer screening with MRI. selleck chemicals The way women think of MRI and mammography is influenced by the screening strategy they are undergoing. Our outcomes can be used for creating information brochures when MRI will be implemented for more women.Most women would prefer screening with MRI. The way women think of MRI and mammography is influenced by the screening strategy they are undergoing. Our outcomes can be used for creating information brochures when MRI will be implemented for more women.N6-methyladenosine (m6A), a ubiquitous internal modification of eukaryotic mRNAs, plays a vital role in almost every aspect of mRNA metabolism. However, there is little evidence documenting the role of m6A in regulating alternative polyadenylation (APA) in plants. APA is controlled by a large protein-RNA complex with many components, including CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30). In Arabidopsis, CPSF30 has two isoforms and the longer isoform (CPSF30-L) contains a YT512-B Homology (YTH) domain, which is unique to plants. In this study, we showed that CPSF30-L YTH domain binds to m6A in vitro. In the cpsf30-2 mutant, the transcripts of many genes including several important nitrate signaling-related genes had shifts in polyadenylation sites that were correlated with m6A peaks, indicating that these gene transcripts carrying m6A tend to be regulated by APA. Wild-type CPSF30-L could rescue the defects in APA and nitrate metabolism in cpsf30-2, but m6A-binding-defective mutants of CPSF30-L could not. Taken together, our results demonstrated that m6A modification regulates APA in Arabidopsis and revealed that the m6A reader CPSF30-L affects nitrate signaling by controlling APA, shedding new light on the roles of the m6A modification during RNA 3'-end processing in nitrate metabolism.The biological functions of the epitranscriptomic modification N6-methyladenosine (m6A) in plants are not fully understood. CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m6A-binding YTH domain. Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m6A-binding function in alternative polyadenylation. Here, we characterized CPSF30-L as an Arabidopsis m6A reader whose m6A-binding function is required for the floral transition and abscisic acid (ABA) response. We found that the m6A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies, where CPSF30-L mainly recognizes m6A-modified far-upstream elements to control polyadenylation site choice. Deficiency of CPSF30-L lengthens the 3' untranslated region of three phenotypes-related transcripts, thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity. Collectively, this study uncovers a new molecular mechanism for m6A-driven phase separation and polyadenylation in plants.Phosphorus is an essential nutrient for plants. It is stored as inorganic phosphate (Pi) in the vacuoles of land plants but as inorganic polyphosphate (polyP) in chlorophyte algae. Although it is recognized that the SPX-Major Facilitator Superfamily (MFS) and VPE proteins are responsible for Pi influx and efflux, respectively, across the tonoplast in land plants, the mechanisms that underlie polyP homeostasis and the transition of phosphorus storage forms during the evolution of green plants remain unclear. In this study, we showed that CrPTC1, encoding a protein with both SPX and SLC (permease solute carrier 13) domains for Pi transport, and CrVTC4, encoding a protein with both SPX and vacuolar transporter chaperone (VTC) domains for polyP synthesis, are required for vacuolar polyP accumulation in the chlorophyte Chlamydomonas reinhardtii. Phylogenetic analysis showed that the SPX-SLC, SPX-VTC, and SPX-MFS proteins were present in the common ancestor of green plants (Viridiplantae). The SPX-SLC and SPX-VTC proteins are conserved among species that store phosphorus as vacuolar polyP and absent from genomes of plants that store phosphorus as vacuolar Pi. By contrast, SPX-MFS genes are present in the genomes of streptophytes that store phosphorus as Pi in the vacuoles. These results suggest that loss of SPX-SLC and SPX-VTC genes and functional conservation of SPX-MFS proteins during the evolution of streptophytes accompanied the change from ancestral polyP storage to Pi storage.

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