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A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin-angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO2/FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections.

Methyl 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate and hygrine are important biosynthetic intermediates for tropane alkaloids. We have developed a concise method to synthesize these two compounds from the key intermediate N-methylpyrrolinium cation. Methyl 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate and hygrine were obtained in four and six steps from commercially available 4,4-diethoxybutylamine with overall yields of 42% and 25%, respectively. Key words: methyl 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate, hygrine, biosynthetic intermediate, tropane alkaloid, N-methylpyrrolinium cation. Le 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate de methyle et l'hygrine sont des intermediaires biosynthetiques importants pour la synthese des alcaloides tropaniques. Nous avons mis au point une methode pour synthetiser ces deux composes tk;4a partir du cation N-methylpyrrolinium comme intermediaire cle. Nous avons obtenu le 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate de methyle et l'hygrine en quatre et six etapes, respectivement, a partir de la 4,4-diethoxybutylamine, qui est commercialement disponible, avec des rendements respectifs de 42 % et de 25 %. [Traduit par la Redaction] Mots-cles : 4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate de methyle, hygrine, intermediaire biosynthetique, alcaloide tropanique, cation N-methylpyrrolinium., Introduction Tropane alkaloids, a family of important natural products found in plants throughout the world, have attracted growing attention becauseoftheir significant biological and pharmacological activity. (1-5) These alkaloids contain complex [...]

Estra-4,9-diene-3,17-dione, an important pharmaceutical intermediate, was synthesized by a three-step sequence from [delta]-lactone 1 in 23.4% overall yield. Reaction of [delta]-lactone 1 and Grignard reagent 2 followed by treatment with Jones reagent resulted in precursor 4. The domino cyclization reaction of 4 with piperidinium acetate gave estra-4,9-diene-3,17-dione. Key words: estra-4,9-diene-3,17-dione, pharmaceutical intermediate, [delta]-lactone, Grignard reaction, Jones reagent, domino cyclization reaction. Nous avons synthétisé l'estra-4,9-diène-3,17-dione, un intermédiaire pharmaceutique d'importance, en trois étapes séquentielles à partir de la [delta]-lactone 1 dans un rendement global de 23,4 %. La réaction entre la [delta]-lactone 1 et le réactif de Grignard 2, suivie d'un traitement par le réactif de Jones a produit le précurseur 4. La réaction de cyclisation domino de l'intermédiaire 4 avec l'acétate de pipéridinium a donné l'estra-4,9-diène-3,17-dione. [Traduit par la Rédaction] Mots-clés : estra-4,9-diène-3,17-dione, intermédiaire pharmaceutique, [delta]-lactone, réaction de Grignard, réactif de Jones, réaction de cyclisation domino., Introduction Estra-4,9-diene-3,17-dione is an important pharmaceutical intermediate in the synthesis of steroids with progestagenic activity (1-3) such as Mifepristone (4-7) and Ulipristal Acetate (8-11) (Fig. 1). Thus, a convenient construction [...]

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched inpatients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases., Cirrhosis is an advanced liver disease resulting from acute or chronic liver injury, including alcohol abuse, obesity and hepatitis virus infection. The prognosis for patients with decompensated liver cirrhosis is [...]

Background The relationship between Klebsiella pneumoniae and nosocomial and community-acquired infections is well known, and K. pneumoniae resistance to most antibiotics is increasing worldwide. In contrast, tigecycline remains active against many bacterial strains, and serves as a last resort for treating multi-drug resistant bacterial infections. That tigecycline nonsusceptibility among K. pneumoniae isolates has been reported worldwide is worrying. However, the mechanisms of tigecycline resistance in K. pneumoniae are less well known. We report the genome sequence and genomic characterization of tigecycline-resistant K. pneumoniae strain 5422 isolated from the bile samples of a patient with cholangiocarcinoma. Results We sequenced the K. pneumoniae strain 5422 genome using next-generation sequencing technologies. Sequence data assembly revealed a 5,432,440-bp draft genome and 57.1% G + C content, which contained 5397 coding sequences. The genome has extensive similarity to other sequenced K. pneumoniae genomes, but also has several resistance-nodulation-cell division (RND) efflux pump genes that may be related to tigecycline resistance. Conclusions K. pneumoniae strain 5422 is resistant to multiple antibiotics. The genome sequence of the isolate and comparative analysis with other K. pneumoniae strains presented in this paper are important for better understanding of K. pneumoniae multi-drug resistance. The RND efflux pump genes identified in the genome indicate the presence of an antibiotic resistance mechanism prior to antibiotics overuse. The availability of the genome sequence forms the basis for further comparative analyses and studies addressing the evolution of the K. pneumoniae drug resistance mechanism and the K. pneumoniae transcriptome. Keywords: Tigecycline-resistant, Klebsiella pneumoniae, Cholangiocarcinoma, Next-generation sequencing, Comparative genomics, Author(s): Beiwen Zheng[sup.1,2] , Ang Li[sup.1,2] , Xiawei Jiang[sup.1,2] , Xinjun Hu[sup.1,2] , Jian Yao[sup.1,2] , Lina Zhao[sup.1,2] , Jinru Ji[sup.1,2] , Min Ye[sup.1,2] , Yonghong Xiao[sup.1,2] and Lanjuan Li[sup.1,2] [...]

The dissemination of Klebsiella pneumoniae carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant Aeromonas taiwanensis isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among A. taiwanensis isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of bla KPC–2 and qnrS2 genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from Aeromonas spp. and IncP-6-type plasmid: 1 from Citrobacter freundii at 74% coverage. A 14,808 bp insertion sequence was observed between merT gene and hypothetical protein in p1713-KPC, which include the quinolone resistance qnrS2 gene. Emergence of plasmid-borned bla KPC and qnrS2 genes from A. taiwanensis isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored. [ABSTRACT FROM AUTHOR]

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Background: Chrysomya megacephala (Fabricius), a prevalent necrophagous blowfly that is easily mass reared, is noted for being a mechanical vector of pathogenic microorganisms, a pollinator of numerous crops, and a resource insect in forensic investigation in the postmortem interval. In the present study, in order to comprehensively understand the physiological and biochemical functions of C. megacephala, we performed RNA-sequencing and digital gene expression (DGE) profiling using Solexa/Illumina sequencing technology. Methodology/Principal Findings: A total of 39,098,662 clean reads were assembled into 27,588 unigenes with a mean length of 768 nt. All unigenes were searched against the Nt database, Nr database, Swiss-Prot, Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genome (KEGG) with the BLASTn or BLASTx algorithm (E-value<0.00001) for annotations. In total, 7,081 unigenes and 14,099 unigenes were functionally classified into 25 COG categories and 240 KEGG pathways, respectively. Furthermore, 20,216 unigenes were grouped into 48 sub-categories belonging to 3 main Gene Ontology (GO) categories (ontologies). Using the transcriptome data as references, we analyzed the differential gene expressions between a soybean oil-fed group (SOF) and a lard oil-fed group (LOF), compared to the negative control group (NC), using the DGE approach. We finally obtained 1,566 differentially expressed genes in SOF/NC, and 1,099 genes in LOF/NC. For further analysis, GO and KEGG functional enrichment were performed on all differentially expressed genes, and a group of differentially expressed candidate genes related to lipometabolism were identified. Conclusions/Significance: This study provides a global survey of C. megacephala and provides the basis for further research on the functional genomics of this insect. [ABSTRACT FROM AUTHOR]

Reduced graphene oxide/SiO2 (RGO/SiO2) serving as a novel spherical support for Ziegler-Natta (Z-N) catalyst is reported. The surface and interior of the support has a porous architecture formed by RGO/SiO2 sandwich structure. The sandwich structure is like a brick wall coated with a graphene layer of concreted as skeleton which could withstand external pressures and endow the structure with higher support stabilities. After loading the Z-N catalyst, the active components anchor on the surface and internal pores of the supports. When the ethylene molecules meet the active centers, the molecular chains grow from the surface and internal catalytic sites in a regular and well-organized way. And the process of the nascent molecular chains filled in the sandwich structure polymerization could ensure the graphene disperse uniformly in the polymer matrix. Compared with traditional methods, the porous spherical graphene support of this strategy has far more advantages and could maintain an intrinsic graphene performance in the nanocomposites. [ABSTRACT FROM AUTHOR]

Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl4-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl4-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4+ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis. [ABSTRACT FROM AUTHOR]

The dissemination of Klebsiella pneumoniae carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant Aeromonas taiwanensis isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among A. taiwanensis isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of bla KPC- 2 and qnrS2 genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from Aeromonas spp. and IncP-6-type plasmid: 1 from Citrobacter freundii at 74% coverage. A 14,808 bp insertion sequence was observed between merT gene and hypothetical protein in p1713-KPC, which include the quinolone resistance qnrS2 gene. Emergence of plasmid-borned bla KPC and qnrS2 genes from A. taiwanensis isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored., (Copyright © 2019 Hu, Yu, Shang, Xu, Guo, Liang, Kang, Song, Sun, Yue, Mao and Zheng.)

Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum MIYAIRI and Bacillus licheniformis Zhengchangsheng on CCl 4 -induced cirrhotic rats. Only administration of LI01 or LI05 prevented liver fibrosis and down-regulated the hepatic expression of profibrogenic genes. Serum endotoxins, bacterial translocations (BTs), and destruction of intestinal mucosal ultrastructure were reduced in rats treated with LI01 or LI05, indicating maintenance of the gut barrier as a mechanism; this was further confirmed by the reduction of not only hepatic inflammatory cytokines, such as TNF-α, IL-6, and IL-17A, but also hepatic TLR2, TLR4, TLR5 and TLR9. Metagenomic sequencing of 16S rRNA gene showed an increase in potential beneficial bacteria, such as Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as Escherichia. These alterations in gut microbiome were correlated with profibrogenic genes, gut barrier markers and inflammatory cytokines. In conclusion, L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis by protecting the intestinal barrier and promoting microbiome health. These results suggest novel strategies for the prevention of liver cirrhosis.

Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3 + CD4 + CD25 + Foxp3 + ), Th17 (CD3 + CD4 + IL-17 + ), and Th1 (CD3 + CD4 + IFN-γ + ) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl 4 . We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl 4 -induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl 4 -induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4 + T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis., Competing Interests: The authors declare no competing financial interests.