Background The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. MethodsWe undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. Findings 1276 COVID-19 survivors completed both visits. The median age of patients was 59•0 years (IQR 49•0-67•0) and 681 (53%) were men. The median follow-up time was 185•0 days (IQR 175•0-198•0) for the 6-month visit and 349•0 days (337•0-361•0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0•0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0•014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0•015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1•43 (95% CI 1•04-1•96) for fatigue or muscle weakness, 2•00 (1•48-2•69) for anxiety or depression, and 2•97 (1•50-5•88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls.Interpretation Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population.
Effective removal of oils, organic solvents and dyes from water is of significant, global importance for environmental and water source protection. Advanced sorbent materials with excellent sorption capacity need to be developed. Here we report porous boron nitride nanosheets with very high specific surface area that exhibit excellent sorption performances for a wide range of oils, solvents and dyes. The nanostructured material absorbs up to 33 times its own weight in oils and organic solvents while repelling water. The saturated boron nitride nanosheets can be readily cleaned for reuse by burning or heating in air because of their strong resistance to oxidation. This easy recyclability further demonstrates the potential of porous boron nitride nanosheets for water purification and treatment.
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using FRET-based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.Accurate chromosome segregation during cell division is essential to maintain genome integrity. Prior to segregation, kinetochores of sister chromatids attach to microtubules from opposite spindle poles (bi-orientation). This configuration is achieved through a trial-and-error process in which correct attachments exert tension across the centromere, which stabilizes kinetochore-microtubule interactions. Incorrect attachments, for example if both sister chromatids attach to a single spindle pole, exert less tension and are destabilized, providing a new opportunity to bi-orient (1,2). How tension is coupled to kinetochore-microtubule stability is not known.The mitotic kinase Aurora B (Ipl1 in budding yeast) localizes to the inner centromere, between sister kinetochores, and destabilizes microtubule attachments by phosphorylating kinetochore substrates, including Dam1 and the Ndc80 complex (3-10). An appealing model is that Aurora B substrates are selectively phosphorylated at incorrect attachments. To test this model we first examined phosphorylation of CENP-A Ser-7, a known kinetochore substrate (11). We used an assay in which Aurora B inhibition leads to a high frequency of syntelic attachment errors, with sister chromatids connected to a single spindle pole (6) (Fig. S1A). We compared phospho-CENP-A staining at correct and incorrect attachments 10 min after removing the reversible Aurora B kinase inhibitor ZM447439 (12), which re-activates Aurora B. Phospho-** Publisher's Disclaimer: This manuscript has been accepted for publication in Science. This version has not undergone final editing.Please refer to the complete version of record at http://www.sciencemag.org/. The manuscript may not be reproduced or used in any manner that does not fall within the fair use provisions of the
Summary Accurate chromosome segregation requires carefully regulated interactions between kinetochores and microtubules, but how plasticity is achieved to correct diverse attachment defects remains unclear. Here, we demonstrate that Aurora B kinase phosphorylates three spatially distinct targets within the conserved outer kinetochore KNL1/Mis12 complex/Ndc80 complex (KMN) network, the key player in kinetochore-microtubule attachments. The combinatorial phosphorylation of the KMN network generates graded levels of microtubule binding activity, with full phosphorylation severely compromising microtubule binding. Altering the phosphorylation state of each protein causes corresponding chromosome segregation defects. Importantly, the spatial distribution of these targets along the kinetochore axis leads to their differential phosphorylation in response to changes in tension and attachment state. In total, rather than generating exclusively binary changes in microtubule binding, our results suggest a mechanism for the tension-dependent fine tuning of kinetochore-microtubule interactions.
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