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Background: Arteriovenous fistula (AVF) is considered to be the best choice of vascular access, but the maturation rate and patency rate of AVF are not satisfactory. Many studies have explored the influencing factors of AVF failure but do not involve the direct relationship between monocyte count and AVF failure. This study aims to explore the relationship between monocyte count and AVF dysfunction related to stenosis. Methods: From September 2017 to September 2018, basic clinical data and laboratory parameters of patients were collected. All included patients were followed up to September 2019. The stenosis-related AVF failure events that occurred after the patient included in the study and the time of their occurrence were recorded. All patients were divided into 3 groups based on the tertile of monocyte count. Kaplan-Meier method was used to compare the patency rate of AVF in each group. The effects of variables on AVF failure were analyzed. A multivariate Cox regression model with p < 0.05 was included in the univariate Cox regression analysis. Results: A total of 120 patients were included in this study. According to the recorded baseline monocyte count levels, they were divided into 3 groups according to their tertiles, 34 cases in the T1 group (T1 < 0.32 × 109/L), 44 cases in the T2 group (0.32 ≤ T2 < 0.51 × 109/L), and 42 cases in T3 group (T3 ≥0.51 × 109/L). After a median follow-up of 20 months, a total of 31 AVF failure events occurred. Kaplan-Meier survival curves showed that patients with a baseline monocyte count ≥0.51 × 109/L had the lowest patency rate of AVF (log-rank test χ2 = 7.525, p = 0.023). After adjusting to basic clinical data and biochemical indicators, there were statistically significant differences in patency rates of the 3 groups (hazard ratio = 2.774, 95% CI = 1.092–7.043). Conclusion: Monocyte count ≥0.51 × 109/L is an independent risk factor for AVF failure, and AVF failure caused by monocytes may be driven by inflammation. [ABSTRACT FROM AUTHOR]

In this study, l‐isoleucine production in Corynebacterium glutamicum WM001 was improved by deleting three genes in the genome, replacing the native promoter of ilvA in the genome, and overexpression of five genes in an alr‐based auxotrophic complementation expression system. The three genes deleted in the genome are alaT, brnQ, and alr. Deletion of alaT improved l‐isoleucine production by increasing the supply of pyruvate, whereas deletion of brnQ improved l‐isoleucine production by blocking the uptake of extracellular l‐isoleucine. Exchange of the native promoter of ilvA with promoter tac or tacM could contribute to l‐isoleucine production by increasing 2‐ketobutyric acid; tac is better than tacM for improving l‐isoleucine yield. Different combinations of the genes ilvBN, ppnK, lrp, and brnFE were overexpressed in an alr‐based auxotrophic complementation expression system to further improve l‐isoleucine production, and the best yield after 72‐H flask fermentation was obtained from the strain WM005/pYCW‐1‐ilvBN2‐ppnK1. Without addition of any antibiotics, WM005/pYCW‐1‐ilvBN2‐ppnK1 could produce 32.1 g/L l‐isoleucine after 72‐H fed‐batch fermentation, which is 34.3% increase compared with the original strain WM001. [ABSTRACT FROM AUTHOR]

Background Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. Methods We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. Results We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. Conclusions We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. More than 4 million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of 11 May 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. In addition, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. Highlights: SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact.A cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19.Impaired acquired immune responses and uncontrolled inflammatory innate responses may be associated with the mechanism of the cytokine storm in COVID‐19.Early control of the cytokine storm through therapies, such as immunomodulators and cytokine antagonists, is essential to improve the survival rate of patients with COVID‐19. [ABSTRACT FROM AUTHOR]

The present study aimed to identify new key genes as potential biomarkers for the diagnosis, prognosis or targeted therapy of clear cell renal cell carcinoma (ccRCC). Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus. GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples. The Database for Annotation, Visualization and Integrated Discovery was utilized for functional and pathway enrichment analysis. STRING v10.5 and Molecular Complex Detection were used for protein-protein interaction (PPI) network construction and module analysis, respectively. Regulation network analyses were performed with the WebGestal tool. UALCAN web-portal was used for expression validation and survival analysis of hub genes in ccRCC patients from The Cancer Genome Atlas (TCGA). A total of 65 up- and 164 downregulated genes were identified as DEGs. DEGs were enriched with functional terms and pathways compactly related to ccRCC pathogenesis. Seventeen hub genes and one significant module were filtered out and selected from the PPI network. The differential expression of hub genes was verified in TCGA patients. Kaplan-Meier plot showed that high mRNA expression of enolase 2 (ENO2) was associated with short overall survival in ccRCC patients (P=0.023). High mRNA expression of cyclin D1 (CCND1) (P<0.001), fms related tyrosine kinase 1 (FLT1) (P=0.004), plasminogen (PLG) (P<0.001) and von Willebrand factor (VWF) (P=0.008) appeared to serve as favorable factors in survival. These findings indicate that the DEGs may be key genes in ccRCC pathogenesis and five genes, including ENO2, CCND1, PLT1, PLG and VWF, may serve as potential prognostic biomarkers in ccRCC. [ABSTRACT FROM AUTHOR]