In this study, three up-flow fixed-bed bioreactors, named as A, B, and C, packed with polycaprolactone (PCL) under different filling ratios (31%, 62%, and 93%, respectively), were investigated over a long period (96 days). During the stable period, the mean effluent NO 3 - - N concentrations in reactors A, B, and C were 1.35 ± 0.50, 1.07 ± 0.41, and 1.03 ± 0.27 mg/L, respectively, which showed the removal of NO 3 - - N was not closely related to filling ratio (p > 0.05, one-way ANOVA). However, it was found that biomass in reactor A was 2.13 and 5.55 times in B and C, respectively. Excessively thick biofilm refrained the enzymatic hydrolysis of PCL and biofilm's specific denitrification rate (SDNR). Backwash stimulated organic matter release and enabled biofilm to restore its denitrification activity. The maximum cycle of backwash was 6 days for the lowest filling ratio reactor. Additionally, the utilization rates for denitrification were 83.3%, 86.4%, and 60.5% in reactors A, B, and C, respectively, which was higher after backwash than before backwash. PRACTITIONER POINTS Excessively thick biofilm refrained the enzymatic hydrolysis of PCL. Backwash stimulated organic matter release and enabled biofilm to restore its denitrification activity. The maximum cycle of backwash was 6 days for the lowest filling ratio reactor. A higher utilization rate of PCL for denitrification was observed after backwash.Heterogeneity of leukemia stem cells (LSCs) is involved in their collective chemoresistance. To eradicate LSCs, it is necessary to understand the mechanisms underlying their heterogeneity. Here, we aimed to identify signals responsible for heterogeneity and variation of LSCs in human acute myeloid leukemia (AML). Monitoring expression levels of endothelial cell-selective adhesion molecule (ESAM), a hematopoietic stem cell-related marker, was useful to detect the plasticity of AML cells. While healthy human hematopoietic stem/progenitor cells robustly expressed ESAM, AML cells exhibited heterogeneous ESAM expression. Interestingly, ESAM- and ESAM+ leukemia cells obtained from AML patients were mutually interconvertible in culture. KG1a and CMK, human AML clones, also represented the heterogeneity in terms of ESAM expression. Single cell culture with ESAM- or ESAM+ AML clones recapitulated the phenotypic interconversion. The phenotypic alteration was regulated at the gene expression level, and RNA sequencing revealed activation of TGFβ signaling in these cells. AML cells secreted TGFβ1, which autonomously activated TGFβ pathway and induced their phenotypic variation. Surprisingly, TGFβ signaling blockade inhibited not only the variation but also the proliferation of AML cells. Therefore, autonomous activation of TGFβ signaling underlies the LSC heterogeneity, which may be a promising therapeutic target for AML.Ongoing oscillatory neural activity before stimulus onset influences subsequent visual perception. Specifically, both the power and the phase of oscillations in the alpha-frequency band (9-13 Hz) have been reported to predict the detection of visual stimuli. Up to now, the functional mechanisms underlying pre-stimulus power and phase effects on upcoming visual percepts are debated. Here, we used magnetoencephalography recordings together with a near-threshold visual detection task to investigate the neural generators of pre-stimulus power and phase and their impact on subsequent visual-evoked responses. Pre-stimulus alpha-band power and phase opposition effects were found consistent with previous reports. Source localization suggested clearly distinct neural generators for these pre-stimulus effects Power effects were mainly found in occipital-temporal regions, whereas phase effects also involved prefrontal areas. In order to be functionally relevant, the pre-stimulus correlates should influence post-stimulus processing. Using a trial-sorting approach, we observed that only pre-stimulus power modulated the Hits versus Misses difference in the evoked response, a well-established post-stimulus neural correlate of near-threshold perception, such that trials with stronger pre-stimulus power effect showed greater post-stimulus difference. By contrast, no influence of pre-stimulus phase effects were found. In sum, our study shows distinct generators for two pre-stimulus neural patterns predicting visual perception, and that only alpha power impacts the post-stimulus correlate of conscious access. This underlines the functional relevance of prestimulus alpha power on perceptual awareness, while questioning the role of alpha phase.The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second-generation H1 -antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described. Here, we discuss the most promising predictors of response and nonresponse to these treatments in CSU. A systematic search was performed by two independent researchers using the MEDLINE/PubMed database with specific keywords and 73 studies included in the review. Levels of evidence were categorized as strong (robust predictors), weak (emerging predictors) or no association, based on the outcome and number of studies available. High disease activity, high levels of C-reactive protein and D-dimer are robust predictors for a poor or no response to sgAHs. Poor or no response to omalizumab is robustly predicted by low serum levels of total IgE. A good response to cyclosporine is robustly predicted by a positive basophil histamine release assay, whereas low total IgE is an emerging predictor. The response to treatment with sgAHs, omalizumab and cyclosporine can be predicted by the use of markers that are readily available in routine clinical practice. Further studies are needed to confirm these predictors. Multiple sclerosis (MS) is a rare neurological disease addressed by only few epidemiological studies in China. https://www.selleckchem.com/products/bupivacaine.html This population-based study aimed to estimate the prevalence of MS in China by using national medical insurance databases. Data from the Urban Employee Basic Medical Insurance database and the Urban Residence Basic Medical Insurance database, which were collected during 2012 to 2016 and included approximately 0.20 billion residents in six provinces, were used in this population-based study. The prevalent patients with MS were identified via diagnostic text or disease codes. The crude prevalence in 2016 was 2.44 per 100,000 population (95% confidence interval (CI) 2.18-2.72), with the prevalence in females being higher than that in males. The standardized prevalence (based on 2010 Chinese census data) was 2.29 (95% CI 2.21-2.38). The prevalence in both sexes in 2016 increased up to the age range of 30-34 years. Subsequently, the female prevalence declined with increasing age, but male prevalence stabilized with increasing age.