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[Display omitted] • Enterococci with optrA increased in mesophilic and thermophilic anaerobic digestion. • IS 1216E in plasmid plays key role in horizontal transfer of optrA. • Chromosomal optrA linked to Tn 554 spread vertically in dominate E. faecalis ST631. • Hyper-thermophilic anaerobic pretreatment reduced plasmid-borne optrA in enterococci. The extensive use of florfenicol in poultry industry results in the emergence of optrA gene, which also confers resistance to clinically important antibiotic linezolid. This study investigated the occurrence, genetic environments, and removal of optrA in enterococci in mesophilic (37 °C) and thermophilic (55 °C) anaerobic digestion systems, and a hyper-thermophilic (70 °C) anaerobic pretreatment system for chicken waste. A total of 331 enterococci were isolated and analyzed for antibiotic resistance against linezolid and florfenicol. The optrA gene was frequently detected in enterococci from chicken waste (42.7%) and effluents from mesophilic (72%) and thermophilic (56.8%) reactors, but rarely detected in the hyper-thermophilic (5.8%) effluent. Whole-genome sequencing revealed that optrA -carrying Enterococcus faecalis sequence type (ST) 368 and ST631 were the dominant clones in chicken waste, and they remained dominant in mesophilic and thermophilic effluents, respectively. The plasmid-borne IS 1216E - fexA - optrA - erm (A)-IS 1216E was the core genetic element for optrA in ST368, whereas chromosomal Tn 554 - fexA - optrA was the key one in ST631. IS 1216E might play a key role in horizontal transfer of optrA due to its presence in different clones. Hyper-thermophilic pretreatment removed enterococci with plasmid-borne IS 1216E - fexA - optrA - erm (A)-IS 1216E. A hyper-thermophilic pretreatment is recommended for chicken waste to mitigate dissemination of optrA from animal waste to the environment. [ABSTRACT FROM AUTHOR]

Diverse antibiotic-resistance genes (ARGs) are frequently reported to have high prevalence in veterinary manure samples due to extensive use of antibiotics in farm animals. However, the characteristics of the distribution and transmission of ARGs among bacteria, especially among different species of multiple antibiotic-resistant bacteria (MARB), have not been well explored. By applying high-throughput sequencing methods, our study uncovered a vast MARB reservoir in livestock manure. The genera Escherichia , Myroides , Acinetobacter , Proteus , Ignatzschineria , Alcaligenes , Providencia and Enterococcus were the predominant cultivable MARB, with compositions of 40.6%–85.7%. From chicken manure isolates, 33 MARB were selected for investigation of the molecular characteristics of antibiotic resistance. A total of 61 ARGs and 18 mobile genetic elements (MGEs) were investigated. We found that 47 ARGs were widely distributed among the 33 MARB isolates. Each isolate carried 27–36 genes responsible for resistance to eight classes of antibiotics frequently used in clinic or veterinary settings. ARGs to the six classes of antibiotics other than streptogramins and vancomycin were present in all 33 MARB isolates with a prevalence of 80%–100%. A total of 12 MGEs were widely distributed among the 33 MARB, with int I1, IS26, ISaba1, and ISEcp1 simultaneously present in 100% of isolates. In addition, 9 gene cassettes within integrons and ISCR1 were detected among MARB isolates encoding resistance to different antibiotic classes. This is the first report revealing the general co-presence of multiple ARGs, various MGEs and ARG cassettes in different species of individual MARB isolates in chicken manure. The results highlight a much higher risk of ARGs spreading through livestock manure to humans than we expected. [ABSTRACT FROM AUTHOR]

• Thirteen key flavor compounds are most likely to be important for wine quality. • Twelve taste-active compounds had a strong correlation with sensory attributes. • Nine flavor compounds had a strong correlation with sensory attributes. This study is sought to identify the components in greengage wine that predict the sensory properties. Taste-active compounds and aroma-active compounds of 20 commercially available greengage wines from different regions were characterized. The relationship between these compounds, wine samples and sensory attributes was modeled by partial least squares regression. The regression analysis indicated the taste-active compounds, alanine, leucine, proline, glutamic acid, lysine, malic acid, citric acid, sucrose, glucose, gallic acid, caffeic acid and tannin made a great contribution to the characteristic taste or mouthfeel of greengage wine. Meanwhile, the aroma-active compounds, including ethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, 3-methylbutanol, 5-hydroxymethylfurfural, octanoic acid and benzaldehyde, modeled well with the flavor characteristic of greengage wine. The study revealed new insights into the relationship between chemistry and wine sensory characters, which has implications for developing an objective measurement system for determining greengage wine quality. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Escherichia coli and antibiotic-resistance genes (ARGs) present a danger to public health. However, information on the dissemination potentials of antibiotic resistance among bacteria from different environments is lacking. We isolated multiple antibiotic-resistant Escherichia spp. from animal farms, hospitals, and municipal wastewater-treatment plants (MWWTPs) using culture-based methods, and carried out resistance phenotype and gene analyses. Thirty-five isolates of multiple antibiotic-resistant Escherichia spp. were further screened to detect 61 ARGs, 18 mobile genetic elements (MGEs), and gene cassettes. The isolates from livestock manure and MWWTPs showed greater diversity in plasmid profiling than hospital wastewater. Each Escherichia sp. carried 21–26 ARGs and 8–12 MGEs. In addition, 11 gene cassettes were detected in 34 Escherichia isolates, with greater diversity in livestock manure and MWWTPs than in hospital wastewater. The results indicated that the potential for ARG transfer was higher in livestock manure and MWWTPs compared with human clinical sources, possibly related to the high occurrence of both residual antibiotics and heavy metals in these environments. Image 1 • The transfer potential of ARGs was compared in Escherichia from different sources. • Each of the Escherichia strains carried at least 1 plasmid, 21 ARGs and 8 MGEs. • High prevalence of gene bla CTX-M was detected in the Escherichia isolates. • Higher ARGs transfer potential in livestock manure and MWWTPs than hospital source. [ABSTRACT FROM AUTHOR]

• DOC was the first factor affecting browning of pear wine. • Total phenols was the second factor affecting browning of pear wine. • Browning in pear wine was dominated by non-enzymatic browning. • OPLS model accurately predicted the browning degree according to the quality index. The effects of different dissolved oxygen concentrations (DOC) on the browning degree, amino acids, total phenols, reducing sugars, polyphenoloxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL) of pear wine, and the relationship between various quality indicators and browning degree were investigated. Dynamic model fitting analysis of the changes of physiochemical indicators of pear wine in the storage process were performed. The importance of the physiochemical indicators effect on the browning of pear wine during the storage process was analyzed by OPLS (orthogonal partial least squares discriminant analysis), and the effect of dissolved oxygen on the browning of pear wine was systematically revealed. The results showed that dissolved oxygen, total phenols and amino acids had the greatest influence on the browning degree of pear wine. It provided a theoretical basis for revealing the browning mechanism and inhibiting the browning of pear wine. [ABSTRACT FROM AUTHOR]

[Display omitted] • MeHg may induce inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome via ROS production. • Induction of autophagy can prevent the neurotoxicity of MeHg. • There is an association between the inflammatory response and autophagy in BV2 cells induced by MeHg. Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress. [ABSTRACT FROM AUTHOR]

Histone lysine-specific demethylase 1 (LSD1) is a promising target for cancer therapy. Here, we performed the design, synthesis, and extensive structure-activity relationship (SAR) studies based on our previously discovered natural LSD1 inhibitor, higenamine. We found that the tetracyclic tetrahydroisoquinoline FY-21 is a potent and selective inhibitor of LSD1 (IC 50 = 340 nM). FY-21 inhibited leukemia cell proliferation and colony formation and increased the level of p53 expression. Meanwhile, FY-21 reduced the mRNA levels of the transcription factors HOXA9 and MEIS1. Furthermore, FY-21 significantly induced leukemia cell differentiation. In vivo studies showed that FY-21 prolonged the survival rate of leukemia mice. Collectively, FY-21 is a potent, selective LSD1 inhibitor and can serve as a lead compound for the development of novel and highly effective LSD1 inhibitors for AML treatment. New tetrahydroisoquinoline as potent and selective LSD1 inhibitor for AML treatment. [Display omitted] • FY-21 was identified as a novel LSD1 inhibitor. • FY-21 exhibited potent antiproliferation activity against MLL-rearranged leukemia cells. • FY-21 induced cell apoptosis in MLL-rearranged leukemia cells by upregulating the expression of p53. • In vivo anti-tumor studies showed that FY-21 significantly extended the lifespan of leukemia mice. [ABSTRACT FROM AUTHOR]

Clostridium difficile is the causative pathogen for antibiotic-related nosocomial diarrhea. For epidemiological study and identification of virulent clones, a new binary typing method was developed for C. difficile in this study. The usefulness of this newly developed optimized 10-loci binary typing method was compared with two widely used methods ribotyping and multilocus sequence typing (MLST) in 189 C. difficile samples. The binary typing, ribotyping and MLST typed the samples into 53 binary types (BTs), 26 ribotypes (RTs), and 33 MLST sequence types (STs), respectively. The typing ability of the binary method was better than that of either ribotyping or MLST expressed in Simpson Index (SI) at 0.937, 0.892 and 0.859, respectively. The ease of testing, portability and cost-effectiveness of the new binary typing would make it a useful typing alternative for outbreak investigations within healthcare facilities and epidemiological research. [ABSTRACT FROM AUTHOR]

Dengue is an acute tropical infectious disease transmitted by mosquitoes, which has posed a major challenge to global public health. Unfortunately, there is a lack of clinically proven dengue-specific drugs for its prevention and treatment. As the pathogenesis of dengue has not been fully elucidated, the development of specific drugs is seriously hindered. This article briefly describes the pathogenesis of dengue fever, the molecular characteristics, and epidemiology of dengue virus, and focuses on the potential small-molecule inhibitors of dengue virus, including on-target and multi-targeted inhibitors, which have been reported in the past two years. [Display omitted] • Potential targets for the development of anti-dengue drugs are summarized. • Elaboration on the infection and pathogenesis of dengue fever. • Natural products or Chinese herbal medicines are important candidate resources for developing anti-dengue drugs. [ABSTRACT FROM AUTHOR]

The anti-HER2 monoclonal antibody trastuzumab is central to the treatment of HER2-positive gastric cancer (GC); however, its responses are limited. HER3 seems to be the preferred dimerization partner with HER2 and is emerging as a key target for complete blockade of downstream pathways and better clinical response. In this study, we report that novel anti-HER3 antibodies (1A5-3D4) that can neutralize multiple modes of HER3 activation, combined with trastuzumab, exhibited synergistic inhibitory effect on the cell proliferation in HER2-positive GC cell lines. Follow-up studies revealed that the combination treatment significantly inhibited phosphorylation of HER3 as well as AKT and ERK signals. In vivo experiments further showed that the anti-tumor effect of trastuzumab was enhanced by its combination with 1A5-3D4 in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. 1A5-3D4 in combination with trastuzumab exhibits a synergistic inhibitory effect on tumor activity, suggesting that targeting both HER2 and HER3 resulted in an improved treatment effects on HER2-positive GC. [ABSTRACT FROM AUTHOR]