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The concise synthesis of dysifragilones A and B and dysidavarones has been accomplished for the first time in a divergent way from a common intermediate. The synthetic route features an intramolecular reductive Heck reaction to construct the 6/5/6/6/-tetracycle of dysifragilones A and B and an intramolecular palladium-catalyzed α-arylation of a sterically hindered ketone to forge the tetracyclo[7.7.1.02,7.010,15]heptadecane core structure of dysidavarone C. The late-stage introduction of amino and ethoxy groups is effective.

A polyphasic taxonomic approach was applied to characterize an anaerobic bacterial strain, 426-9T, that was isolated from human faeces. The strain was Gram-stain-negative, non-motile, non-spore-forming, non-pigmented and rod-shaped. Strain 426-9T grew anaerobically at 20–45 °C (optimally at 37–40 °C) and at pH 6.0–10.0 (optimally at pH 6.0–8.0). The major polar lipids were phosphatidylethanolamine, seven amino phospholipids and three phospholipids. The major fatty acids of strain 426-9T were anteiso-C15 : 0 and iso-C17 : 0 3-OH, and the predominant respiratory quinones were menaquinones MK-9 and MK-10. End-products of glucose fermentation were acetate, propionate, iso-butyrate and iso-pentanoate. 16S rRNA gene sequence analysis showed that strain 426-9T was a member of the genus Parabacteroides . The level of 16S rRNA gene sequence similarity of strain 426-9T to the type species of the genus, Parabacteroides distasonis ATCC 8503T, was 91.0 %. Within the genus Parabacteroides , strain 426-9T was phylogenetically closely related to Parabacteroides johnsonii M-165T (96.0 % 16S rRNA gene sequence similarity). The draft genome of strain 426-9T comprised 5.15 Mb with a DNA G+C content of 45.9 mol%. A total of 4088 genes were predicted and, of those, 3744 were annotated. On the basis of phenotypic, chemotaxonomic and phylogenetic characterization, strain 426-9T represents a novel species within the genus Parabacteroides , for which the name Parabacteroides acidifaciens sp. nov. is proposed. The type strain is 426-9T (=CGMCC 1.13558T=NBRC 113433T).

Sigma-2 receptor (σ

Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b, 3e, 4b, and 4e demonstrated Ki values of 5–6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities.

Sigma-2 receptor (σ2R/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ2 ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ2 ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σ2R/TMEM97. Especially, 4 analogs showed Ki values ranging from 0.38 to 5.1 nM for σ2R/TMEM97 with no or low affinity for sigma-1 receptor (σ1R). Functional assays indicated that these 4 most potent analogs had no effects on intracellular calcium concentration and were classified as putative σ2R/TMEM97 antagonists according to current understanding. The σ2R/TMEM97 has been suggested to play important roles in the central nervous system. Based on published pharmacological and clinical results from several regarded σ2R/TMEM97 antagonists, these analogs may potentially be useful for the treatment of various neurodegenerative diseases.

Our goal is to find out how the passenger number, vehicle type and vehicle displacement influence the PM2.5 concentration in underground parking lots of large shopping centers. To this end, we collected data of PM2.5 concentration in several underground parking lots in CBDs of Changchun. We have some findings from the conducted experiments. First, PM2.5 concentration rises as the the number of passengers carried in the vehicle increases. As for vehicle type and displacement, high-displacement sedans and moderate-displacement SUVs contribute most to PM2.5 concentration inside the parking lots, among which vehicles of older age cause even greater pollution, with PM2.5 concentration averaging 208 μg/m³and 241μg/m³respectively. And high-displacement MPVs have greater influence on PM2.5 concentration than low-displacement ones.

The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34+ cells and CD34+CD38− cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications.

A polyphasic study was conducted to characterize an obligately anaerobic bacterial strain, S15T, that was isolated from Okinawa Trough sediment. Strain S15T was Gram-stain-negative, non-motile and rod-shaped. Spores were not observed. Strain S15T grew anaerobically at 20–35 °C (optimum at 25–30 °C) and at pH range of 6.0–8.5 (optimum at 7.5). Analysis of 16S rRNA gene sequences showed that strain S15T was phylogenetically related to Vallitalea guaymasensis Ra1766G1T (94.0 %) and Vallitalea pronyensis FatNI3T (93.1 %). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The predominant fatty acids of strain S15T were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The draft genome was 5.86 Mb with a DNA G+C content of 33.9 mol %. A total of 5285 genes were predicted and, of those, 4669 genes were annotated. The genome data supported the result that strain S15T assimilated various carbon sources. On the basis of unique phenotypic, chemotaxonomic and phylogenetic comparisons, strain S15T is proposed to represent a novel species within the genus Vallitalea , and the name Vallitalea okinawensis sp. nov. is proposed. The type strain is S15T=CGMCC 1.5231T=KCTC 15675T.

Nomegestrol acetate (NOMAc) is a synthetic progesterone analog and classified as a fourth-generation progestin. It has been approved in many countries for oral contraception, hormonal replacement therapy (HRT), and treatment of various gynecological disorders. There are several synthetic routes reported for the synthesis of NOMAc and they all share the very similar last three to five steps toward the conversion of 6-methylene to 6-methyl-6,7-unsaturated structure. Therefore the final product from different processing routes may have similar impurity profiles. In the analysis of NOMAc, we identified two impurities, impurity A (listed in EP 8.0) and impurity B (not specified in EP 8.0). Both impurities were further confirmed by synthesis. In addition, both impurities and NOMAc were evaluated for their in vitro cytotoxicities against L02 liver cells, mesenchymal stem cells, MCF-7 breast cancer cells, and C33A cervical cancer cells. These three analogs are not cytotoxic to the four cell lines at low concentrations (

The termite gut microbiome is a model system to investigate microbial interactions and their associations with host. For decades, extensive research with molecular tools and conventional cultivation method has been carried out to define the microbial diversity in termite gut. Yet, many bacterial groups of the termite gut microbiome have not been successfully cultivated in laboratory. In this study, we adapted the recently developed microfluidic streak plate (MSP) technique for cultivation of termite gut microbial communities at both aerobic and anaerobic conditions. We found that 99 operational taxonomic units (OTUs) were cultivable by MSP approach and 18 OTUs were documented first time for termite gut microbiota. Further analysis of the bacterial diversities derived by culture‐dependent MSP approach and culture‐independent 16S rRNA gene typing revealed that both methods have bias in recovery of gut microbiota. In total 396 strains were isolated with MSP technique, and potential new taxa at species and/or genus levels were obtained that were phylogenetically related to Burkholderia, Micrococcus, and Dysgonomonas. Results from this study indicate that MSP technique is applicable for cultivating previously unknown and new microbial groups of termite gut microbiota.

A monolayer study on the interaction of human apolipoprotein H (ApoH) and phospholipids is reported in the present work. The initial rate of surface pressure change (dπ/dt)ini is used to characterize the insertion process of ApoH into the phospholipid monolayers spread at the air/water interface. The results show that the value of (dπ/dt)ini of ApoH will rise when the content of DMPS in the DMPS/DMPC monolayer mixture increases, indicating an increase in membrane insertion ability of the protein. The protein adsorption can be screened by sodium ions but not by calcium ions. When the pH is lower than 6, the initial rate of surface pressure change of the protein will increase sharply indicating that acidic environment is an important factor influencing the membrane insertion process of ApoH.

Recent advances in biosensor technology have contributed significantly to our understanding of the mechanisms of molecular recognition processes. In this study, a surface plasmon resonance (SPR)-based optical sensor was employed to study the binding interactions between a series of template/primer double-stranded DNA (dsDNA) and DNA polymerase enzymes containing both polymerase and exonuclease activities. The DNA molecules were immobilized on the SPR gold surface by the controlled assembly of a biotinylated phospholipid monolayer, an avidin monolayer, and a layer of biotinylated DNA. By introducing a number of different mismatches at/near the 3‘-end of the primer, the effects of the mismatches on the overall binding affinities of the Klenow fragment (KF) of Escherichia coli DNA polymerase I and T4 and T7 bacteriophage polymerases were measured. While no obvious trend in the overall binding affinity of the Klenow fragment was observed with the introduction of mismatched base pair(s), its polymerase domain ...

A home-made SPR biosensor was used to monitor the interactions of gp41 with its binding proteins in real time. The result indicates that the polystyrene biosensor film is useful for SPR detection. The binding constants indicate both P45 and P62 have a high affinity to the protein gp41, and suggest that P45 and P62 may be the cellular receptors on human T-, B-lymphocytes and monocytes.