Abstract Neutrophil migration and activation are essential for defense against pathogens. However, this process may also lead to collateral tissue injury. We used microRNA overexpression as a platform and discovered protein-coding genes that regulate neutrophil migration. Here we show that miR-99 decreased the chemotaxis of zebrafish neutrophils and human neutrophil-like cells. In zebrafish neutrophils, miR-99 directly targets the transcriptional factor RAR-related orphan receptor alpha (roraa) . Inhibiting RORα, but not the closely related RORγ, reduced chemotaxis of zebrafish and primary human neutrophils without causing cell death, and increased susceptibility of zebrafish to bacterial infection. Expressing a dominant-negative form of Rorα or disrupting the roraa locus specifically in zebrafish neutrophils reduced cell migration. At the transcriptional level, RORα regulates transmembrane signaling receptor activity and protein phosphorylation pathways. Our results, therefore, reveal previously unknown functions of miR- 99 and RORα in regulating neutrophil migration and anti-microbial defense.
Front Cover Caption: The cover image is based on the Research Article Updated SARS-CoV-2 single nucleotide variants and mortality association by Shuyi Fang et al., https://doi.org/10.1002/jmv.27191.
Recently, the epidemic of novel coronavirus pneumonia (COVID-19) in China and other countries in the world is serious. There are at present no effective treatments for COVID-19. The safety and effectiveness of western anti-coronavirus drugs are under investigation. In many places in China, traditional Chinese medicine (TCM) has been used to treat COVID-19 with a high clinical cure rate. The treatment economics of TCM is good. The immune-regulating and antiviral TCM can enhance human immunity and exert an antiviral effect. They have been widely used in the anti-COVID-19 treatment. We consulted the database of CNKI, Wanfang, VIP and PubMed for screening the immune-regulating and antiviral TCMs (Glycyrrhizae Radix et Rhizoma, Pogostemonis Herba, Lonicerae Japonicae Flos, Scutellariae Radix, Forsythiae Fructus, Magnoliae Officinalis Cortex, Bupleuri Radix, Isatidis Radix, Rhei Radix et Rhizoma, Astragali Radix, and Houttuyniae Herba). This article summarizes the physicochemical and pharmacokinetic characteristics, and the clinical application of the effective components of immune-regulating and antiviral TCM in the prescriptions and Chinese patent medicines, in order to provide a better reference for the clinical application of TCM.
Abstract Since its outbreak in December 2019, COVID-19 has caused 100,5844,555 cases and 2,167,313 deaths as of Jan 27, 2021. Comparing our previous study of SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found out that the SNV clustering had changed considerably since June 2020. Apart from that the group SNVs represented by two non-synonymous mutations A23403G (S: D614G) and C14408T (ORF1ab: P4715L) became dominant and carried by over 95% genomes, a few emerging groups of SNVs were recognized with sharply increased monthly occurrence ratios up to 70% in November 2020. Further investigation revealed that several SNVs were strongly associated with the mortality, but they presented distinct distribution in specific countries, e.g., Brazil, USA, Saudi Arabia, India, and Italy. SNVs including G25088T, T25A, G29861T and G29864A were adopted in a regularized logistic regression model to predict the mortality status in Brazil with the AUC of 0.84. Protein structure analysis showed that the emerging subgroups of non-synonymous SNVs and those mortality-related ones in Brazil were located on protein surface area. The clashes in protein structure introduced by these mutations might in turn affect virus pathogenesis through conformation changes, leading to the difference in transmission and virulence. Particularly, we found that SNVs tended to occur in intrinsic disordered regions (IDRs) of Spike (S) and ORF1ab, suggesting a critical role of SNVs in protein IDRs to determine protein folding and immune evasion.
Four signature groups of frequently occurred single-nucleotide variants (SNVs) were identified in over twenty-eight thousand high-quality and high-coverage SARS-CoV-2 complete genome sequences, representing different viral strains. Some SNVs predominated but were mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguishable evolution patterns over time. A few hundred patients were detected with multiple viral strain-representing mutations simultaneously, which may stand for possible co-infection or potential homogenous recombination of SARS-CoV-2 in environment or within the viral host. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tended to switch between bat RaTG13 coronavirus sequence and Wuhan-Hu-1 genome, indicating the higher genetic instability or tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.
A high-resolution mass spectrometry (HR-MS) method was developed to analyze and identify small molecule compounds in distillery wastewater. According to identification confidence levels, 4 levels of compounds were identified. The five antimicrobial compounds (lactic acid, succinic acid, acetophenone, cinnamic acid, and phenyllactic acid), which shown in high concentrations, were at the highest level of confidence (level 1, confirmed structure). Thus, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify these antimicrobial compounds. The analysis was performed in the selective reaction monitoring (SRM) mode via the electrospray ionization (ESI) source operating in the negative ionization mode. Linear calibration curves were obtained over the concentration range of 50–1000 ng/mL for succinic acid, acetophenone, cinnamic acid, phenyllactic acid, and 375–7500 ng/mL for lactic acid. Precision and recovery of the analytes were all satisfactory (relative standard deviation < 10%). The validated method was successfully applied to quantitative analysis of the five antimicrobial compounds in distillery wastewater. Analyze and identify 4 levels of small molecule compounds in distillery wastewater. Simple method for quantification of five antimicrobial compounds. Column temperature affected the lactic and succinic acid chromatographs significantly.
Abstract Background Aberrant intracellular or intercellular signaling pathways are important mechanisms that contribute to the development and progression of cancer. However, the intercellular communication associated with the development of ccRCC is currently unknown. The purpose of this study was to examine the aberrant tumor cell-to-cell communication signals during the development of ccRCC. Methods We conducted an analysis on the scRNA-seq data of 6 ccRCC and 6 normal kidney tissues. This analysis included sub clustering, CNV analysis, single-cell trajectory analysis, cell–cell communication analysis, and transcription factor analysis. Moreover, we performed validation tests on clinical samples using multiplex immunofluorescence. Results This study identified eleven aberrantly activated intercellular signaling pathways in tumor clusters from ccRCC samples. Among these, two of the majors signaling molecules, MIF and SPP1, were mainly secreted by a subpopulation of cancer stem cells. This subpopulation demonstrated high expression levels of the cancer stem cell markers POU5F1 and CD44 (POU5F1 hi CD44 hi E.T), with the transcription factor POU5F1 regulating the expression of SPP1. Further research demonstrated that SPP1 binds to integrin receptors on the surface of target cells and promotes ccRCC development and progression by activating potential signaling mechanisms such as ILK and JAK/STAT. Conclusion Aberrantly activated tumor intercellular signaling pathways promote the development and progression of ccRCC. The cancer stem cell subpopulation (POU5F1 hi CD44 hi E.T) promotes malignant transformation and the development of a malignant phenotype by releasing aberrant signaling molecules and interacting with other tumor cells.
Streptococcus thermophilus VHProbi R08 is a bacterial strain isolated from fermented sour porridge in northern China. Here, we report the complete genome sequence of VHProbi R08, which comprises 1,848,461 bp, 1,906 protein-coding genes, 57 tRNA genes, and 15 rRNA genes.
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