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Enterovirus A71 (EV-A71) is an important pathogen of severe hand, foot, and mouth disease (HFMD) in young children. This study aimed to retrospectively analyze the molecular epidemiology and recombination of EV-A71 in mainland China during 1987-2017. Phylogenetic tree showed that besides the previously reported subgenotypes A, B5, C0, C2, C3, and C4, a new subgenotype C6 emerged in mainland China. Recombination analysis indicated that C4 EV-A71 was derived from a common ancestor as a "double-recombinant" virus by intertypic recombination between C EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains in P3 region and intratypic recombination between C and B EV-A71 strains in P2 region. The B5 EV-A71 shared high similarity with C EV-A71 in P1 region while it contained an unidentified sequence in P2 and P3 regions with two possible recombination patterns one occurred between C4 EV-A71 and CVA3, CVA5, CVA6, CVA10, and CVA12 stains with one breakpoint in 3C, and the other occurred between C1, C2, C3, and C5 EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains with two breakpoints in the 2A/2B junction and 3C. The C2 EV-A71 was probably a recombinant virus between C4 EV-A71 and CVA8 strains with two breakpoints located in the 5'UTR and 2A/2B junction. Moreover, an incredible recombination of C6 EV-A71 occurred between C4 and C2 EV-A71 with multiple breakpoints. Thus, continuous studies on EV-A71 genome characteristics are still useful and essential for monitoring emergence of new viruses and preventing HFMD outbreaks.One marine bacteria Bacillus pumilus was isolated using allura red as ε-poly-L-lysine (ε-PL) secretion indicator. But actually the product was identified as poly-γ-L-diaminobutanoic acid (γ-PAB) by ionization-time-of-flight mass spectrometry, not coproduced with ε-PL. The polymerization degree of γ-PAB was 4-22, namely short-chain γ-PAB, compared with that in S. celluloflavus, and it exhibited stronger inhibitory activities against yeasts than long-chain γ-PAB but weaker activities against bacteria. The fermentative behavior of B. pumilus was investigated, and the γ-PAB production was 38.6 mg/L in shake flask and was enhanced to 284.2 mg/L in 5-L bioreactor by a pH control strategy. Interestingly, the suitable pH for B. pumilus to produce γ-PAB was 4.8, different from 4.0 for current Streptomyces strains, which suggests a potential new metabolic mechanism in B. pumilus as a novel γ-PAB producer. No studies on short-chain γ-PAB production in bacteria have been reported previously and we considered that this is a new discovery in the field of homopolymer research.A screen-printed electrode (SPE) is described modified with sulfur-tin oxide nanoparticles (S@SnO2NP) for the determination of entacapone (ENT) in the presence of other medicines against Parkinson's disease (PD). The S@SnO2NP was synthesized through the hydrothermal method and used in the modification of the SPE. The smart utilization of the S@SnO2NP and the SPE provided excellent properties such as high surface area and current density amplification by embedding an efficient sensing interface for highly selective electrochemical measurement. Under optimized experimental conditions, the anodic peak current related to the ENT oxidation onto the sensor surface at 0.46 V presented a linear response towards different ENT concentration sin the range 100 nM to 75 μM. The limit of detection (LOD) and electrochemical sensitivity were estimated to be 0.010 μM and 2.27 μA·μM-1·cm-2, respectively. The applicability of the sensor was evaluated during ENT determination in the presence of other conventional medicines againts, including levodopa (LD), carbidopa (CD), and pramipexole (PPX). The results of the analysis of human urine and pharmaceutical formulation as real samples using the developed sensor were in good agreement withre sults of high-performance liquid chromatography (HPLC) as a standard method. These findings demonstrated that the strategy based on the SPE is a cost-effective platform creating a promising candidate for practical determination of ENT in routine clinical testing.Graphical abstract.Liver fibrosis is a continuous wound healing response caused by chronic liver injury, and the activation of hepatic stellate cells (HSCs) is considered as the main event for it. Core fucosylation catalyzed by FUT8 refers to adding the fucosyl moiety to the innermost GlcNAc residue of N-linked oligosaccharides and is involved in many biological processes such as cell differentiation, migration, and signaling transduction. Aberrant core fucosylation is associated with a variety of diseases including cardiovascular disease, tumors and neuroinflammation, but much less is understood in liver fibrosis. Herein, we reported FUT8 mRNA level was increased in patients with liver fibrosis from GEO database and positively correlated with fibrosis progression. FUT8 expression and the core fucosylation were also elevated in TAA-induced mouse liver fibrosis model, and were mainly distributed in the fibrous septum of mouse liver. TGF-β1, as the most pro-fibrogenic cytokine, could promote the expression of FUT8 and total core fucosylation levels in HSCs in vitro. However, up-regulation of FUT8 in turn inhibited TGF-β1-induced trans-differentiation, migration and pro-fibrogenic signaling pathways in HSCs. click here In conclusion, our results suggest that the up-regulation of FUT8 inhibits TGF-β1-induced HSC activation in a negative feedback loop, and provide potential new therapeutic strategy for liver fibrosis by targeting FUT8.O-GlcNAcylation, a single attachment of N-acetylglucosamine (GlcNAc) on serine and threonine residues, plays important roles in normal and pathobiological states of many diseases. Aberrant expression of O-GlcNAc modification was found in many types of cancer including colorectal cancer (CRC). This modification mainly occurs in nuclear-cytoplasmic proteins; however, it can exist in some extracellular and secretory proteins. In this study, we investigated whether O-GlcNAc-modified proteins are present in serum of patients with CRC. Serum glycoproteins of CRC patients and healthy controls were enriched by wheat germ agglutinin, a glycan binding protein specifically binds to terminal GlcNAc and sialic acid. Two-dimensional gel electrophoresis, RL2 O-GlcNAc immunoblotting, affinity purification, and mass spectrometry were performed. The results showed that RL2 O-GlcNAc antibody predominantly reacted against serum immunoglobulin A1 (IgA1). The levels of RL2-reacted IgA were significantly increased while total IgA were not different in patients with CRC compared to those of healthy controls.
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