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The title compound, C32H35NO4, is an unexpected product obtained in the SmI2-mediated radical cross-coupling of a lactam 2-pyridyl sulfone with an arone. The asymmetric unit contains two molecules. In both molecules, the core pyrrolidinone ring adopts an approximate envelope conformation (with the C atom bearling the benzyloxy substituent as the flap) and the cyclohexyl ring has a chair conformation. The relative orientation of the two substitutent groups at the 4- and 5-positions of the pyrrolidinone ring is anti in both molecules, with O(benzyloxy)—C—C—C(benzene) torsion angles of 150.8 (3) and 154.2 (2)°. In the crystal, C—H...O interactions involving carbonyl groups as acceptors lead to the formation of a tape motif propagating parallel to the a-axis direction.

Streptococcus suis is an important zoonotic pathogen. However, identification of virulent S. suis strains is complicated because of the high diversity of the species. Here we evaluated the genetic difference among S. suis strains using comparative genomic hybridization (CGH) and virulence variation in vivo and in vitro. We showed that different clades differed in their ability to activate TLR2/6 in vitro and their capacity to induce cytokine production in vivo as well as their resistance to phagocytosis and survival in vivo. Our data showed the S. suis strains tested can be classified into three groups having differing levels of virulence: epidemic and highly virulent strains were clustered into clade Ia (epidemic and highly virulent group, E/HV group), virulent strains were clustered into clade Ib (virulent group, V group), and intermediately or weakly virulent strains were clustered into other clades (intermediately or weakly virulent group, I/WV group). Our study provided further insight into the genomic and virulence variation of S. suis.

Knowledge about grassland biomass and its dynamics is critical for studying regional carbon cycles and for the sustainable use of grassland resources. In this study, we investigated the spatio-temporal variation of biomass in the Xilingol grasslands of northern China. Field-based biomass samples and MODIS time series data sets were used to establish two empirical models based on the relationship of the normalized difference vegetation index (NDVI) with above-ground biomass (AGB) as well as that of AGB with below-ground biomass (BGB). We further explored the climatic controls of these variations. Our results showed that the biomass averaged 99.01 Tg (1 Tg=10(12) g) over a total area of 19.6 × 10(4) km(2) and fluctuated with no significant trend from 2001 to 2012. The mean biomass density was 505.4 g/m(2), with 62.6 g/m(2) in AGB and 442.8 g/m(2) in BGB, which generally decreased from northeast to southwest and exhibited a large spatial heterogeneity. The year-to-year AGB pattern was generally consistent with the inter-annual variation in the growing season precipitation (GSP), showing a robust positive correlation (R(2)=0.82, P

N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme involved in biological deactivation of N-palmitoylethanolamide (PEA), which exerts anti-inflammatory and analgesic effects through the activation of nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-α). To develop selective and potent NAAA inhibitors, we designed and synthesized a series of derivatives of 1-pentadecanyl-carbonyl pyrrolidine (compound 1), a general amidase inhibitor. Structure activity relationship (SAR) studies have identified a compound 16, 1-(2-Biphenyl-4-yl)ethyl-carbonyl pyrrolidine, which has shown the highest inhibition on NAAA activity (IC(50) =2.12 ± 0.41 µM) and is characterized as a reversible and competitive NAAA inhibitor. Computational docking analysis and mutagenesis study revealed that compound 16 interacted with Asparagine 209 (Asn(209)) residue flanking the catalytic pocket of NAAA so as to block the substrate entrance. In vitro pharmacological studies demonstrated that compound 16 dose-dependently reduced mRNA expression levels of iNOS and IL-6, along with an increase of intracellular PEA levels, in mouse macrophages with lipopolysaccharides (LPS) induced inflammation. Our study discovered a novel NAAA inhibitor, compound 16, that could serve as a potential anti-inflammatory agent.

Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. Infections in humans have been sporadic worldwide but two severe outbreaks occurred in China in recent years, while infections in pigs are a major problem in the swine industry. Some S. suis strains are more pathogenic than others with 2 sequence types (ST), ST1 and ST7, being well recognized as highly pathogenic. We analyzed 31 isolates from 23 serotypes and 25 STs by NimbleGen tiling microarray using the genome of a high pathogenicity (HP) ST1 strain, GZ1, as reference and a new algorithm to detect gene content difference. The number of genes absent in a strain ranged from 49 to 225 with a total of 632 genes absent in at least one strain, while 1346 genes were found to be invariably present in all strains as the core genome of S. suis, accounting for 68% of the GZ1 genome. The majority of genes are located in chromosomal blocks with two or more contiguous genes. Sixty two blocks are absent in two or more strains and defined as regions of difference (RDs), among which 26 are putative genomic islands (GIs). Clustering and statistical analyses revealed that 8 RDs including 6 putative GIs and 21 genes within these RDs are significantly associated with HP. Three RDs encode known virulence related factors including the extracellular factor, the capsular polysaccharide and a SrtF pilus. The strains were divided into 5 groups based on population genetic analysis of multilocus sequence typing data and the distribution of the RDs among the groups revealed gain and loss of RDs in different groups. Our study elucidated the gene content diversity of S. suis and identified genes that potentially promote HP.

The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens.Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis.The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens.Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.

Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning) method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH) to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE) analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+) strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes.

To investigate evolution of soil arching during suffusion in gap-graded soils, a new suffusion apparatus was developed for trapdoor tests under a horizontal seepage flow. Glass beads with fine-grain contents ranging from 15% to 45% were adopted to represent coarse-grain controlled soils and fine-grain controlled soils. Coupled computational fluid dynamics (CFD) and discrete element method (DEM) models were developed to further investigate the evolution of soil arching from microscopic views. At the early stage of suffusion, soil arching degraded rapidly under seepage loads in both coarse-grain controlled and fine-grain controlled soils due to the compaction of soil skeleton and the clogging of voids, which increased in the number of fine particles connected to the stress-transfer matrix. At the later stage, soil arching was nearly maintained as the soil skeleton became stable in the coarse-grain controlled soils. In the fine-grain controlled soils, soil arching degraded continuously due to continuous loss of fine particles connected to the stress-transfer matrix. The decrease in the contact number of fine particles also made the soil skeleton more vulnerable to suffusion. The degradation of soil arching resulted in an increase of surface displacement and a decrease of soil arching height in fine-grain controlled soils. Key words: soil arching, suffusion, trapdoor test, CFD-DEM, strong force chain, 1. Introduction Soil arching is generally defined as the stress redistribution due to the relative displacement between a yielding soil mass and its adjacent soil masses (Terzaghi 1943). This phenomenon [...]