Two new sesquiterpene glycosides from <i>Dendrobium findleyanum</i>

One new ylangene-type sesquiterpene glycoside, findlayanoside C (1), and one new picrotoxane-type sesquiterpene glycoside, findlayanoside D (3), together with five known sesquiterpene glycosides, dendrofindlayanoside C (2), dendronobiloside B (4), dendronobiloside A (5), dendroside F (6) and dendromoniliside D (7), have been isolated from the stems of Dendrobium findleyanum. The structures of compounds 1 and 3 were elucidated by means of extensive spectroscopic analyses, and their absolute configuration were confirmed by electronic circular dichroism (ECD) calculations. Cytotoxic activity assays against SMMC-7721, A-549 and MCF-7 human cancer cell lines revealed IC50 values of 10.12, 12.32 and 14.13 μM for compound 1, and of 9.25, 13.16 and 16.26 μM for compound 2. This study enriches the anti-tumour sesquiterpenoids composition of D. findleyanum.</p

Understanding the Relationship between Cetane Number and the Ignition Delay in Shock Tubes for Different Fuels Based on a Skeletal Primary Reference Fuel (<i>n</i>‑Hexadecane/Iso-cetane) Mechanism

A new skeletal oxidation mechanism for the primary reference fuel (PRF) was established with a decoupling methodology. The mechanism is composed of <i>n</i>-hexadecane and iso-cetane submechanisms, containing 44 species and 139 reactions. Using the present mechanism, the relationship between cetane number and the ignition delay in shock tubes was investigated. First, based on the ignition delay data in shock tubes, the cetane number of various fuels was estimated using the present PRF mechanism and a weighted least-squares method. The prediction of cetane number investigated in this study primarily focused on the operating conditions of practical diesel engines (i.e., the equivalence ratio of 1.0 and pressures from 19–80 atm), which encompass the cetane number from 15 to 100. Under the test operating conditions, the mean absolute deviation of the predicted cetane number is within 3.327. Furthermore, according the cetane number of different fuels, the ignition delays in shock tubes were reproduced by the present mechanism focusing on a wide range of equivalence ratios (0.5–3.0) and pressures (20–50 atm). The results indicated that the predicted IDs of alkanes were more accurate than those of other types of fuels and blended fuels because of the consistent molecular structure of the <i>n</i>-hexadecane/iso-cetane used in the present mechanism. Because of the compact size of the skeletal mechanism, its application can considerably reduce the computational time for 3D combustion simulations, especially for practical fuels with complicated compositions

Understanding the Relationship between Cetane Number and the Ignition Delay in Shock Tubes for Different Fuels Based on a Skeletal Primary Reference Fuel (<i>n</i>‑Hexadecane/Iso-cetane) Mechanism

A new skeletal oxidation mechanism for the primary reference fuel (PRF) was established with a decoupling methodology. The mechanism is composed of <i>n</i>-hexadecane and iso-cetane submechanisms, containing 44 species and 139 reactions. Using the present mechanism, the relationship between cetane number and the ignition delay in shock tubes was investigated. First, based on the ignition delay data in shock tubes, the cetane number of various fuels was estimated using the present PRF mechanism and a weighted least-squares method. The prediction of cetane number investigated in this study primarily focused on the operating conditions of practical diesel engines (i.e., the equivalence ratio of 1.0 and pressures from 19–80 atm), which encompass the cetane number from 15 to 100. Under the test operating conditions, the mean absolute deviation of the predicted cetane number is within 3.327. Furthermore, according the cetane number of different fuels, the ignition delays in shock tubes were reproduced by the present mechanism focusing on a wide range of equivalence ratios (0.5–3.0) and pressures (20–50 atm). The results indicated that the predicted IDs of alkanes were more accurate than those of other types of fuels and blended fuels because of the consistent molecular structure of the <i>n</i>-hexadecane/iso-cetane used in the present mechanism. Because of the compact size of the skeletal mechanism, its application can considerably reduce the computational time for 3D combustion simulations, especially for practical fuels with complicated compositions

Fine Mapping of a Region of Chromosome 11q23.3 Reveals Independent Locus Associated with Risk of Glioma

<div><h3>Background</h3><p>A single nucleotide polymorphism (SNP) at locus 11q23.3 (rs498872) in the near 5′-UTR of the <em>PHLDB1</em> gene was recently implicated as a risk factor for gliomas in a genome-wide association study, and this involvement was confirmed in three additional studies.</p> <h3>Methodology/Principal Findings</h3><p>To identify possible causal variants in the region, the authors genotyped 15 tagging SNPs in the 200 kb genomic region at 11q23.3 locus in a Chinese Han population-based case-control study with 983 cases and 1024 controls. We found evidence for an association between two independent loci (both the <em>PHLDB1</em> and the <em>ACRN1</em> genes) and a predisposition for gliomas. Among the multiple significant SNPs in the <em>PHLDB1</em> gene region, the rs17749 SNP was the most significant [<em>P</em> = 1.31×10⁻⁶ in a recessive genetic model]. Additionally, two novel SNPs (rs2236661 and rs494560) that were independent of rs17749 were significantly associated with glioma risk in a recessive genetic model [<em>P</em> = 1.31×10⁻⁵ and <em>P</em> = 3.32×10⁻⁵, respectively]. The second novel locus was within the <em>ARCN1</em> gene, and it was associated with a significantly reduced risk for glioma.</p> <h3>Conclusions/Significance</h3><p>Our data strongly support <em>PHLDB1</em> as a susceptibility gene for glioma, also shedding light on a new potentially candidate gene, <em>ARCN1</em>.</p> </div

Characteristics of the cases and controls in a Chinese study population.

<p>Bold characters indicate corresponding <i>P</i> values are less than 0.05.</p>a<p>Other gliomas including oligodendrogliomas, ependymomas, ormixed gliomas.</p

Genotype frequencies of five glioma susceptibility SNPs among cases and controls and their association with glioma risk in a Chinese population.

<p>Bold characters indicate corresponding <i>P</i> values are less than 6.67×10⁻⁴.</p>a<p>Adjusted for age and gender.</p>b<p>Other types including astrocytic glioma, oligodendrogliomas, ependymomas, ormixed gliomas.</p

A schematic view of genetic association between SNPs at 11q23.3 and glioma risk in Chinese Han populations.

<p>A schematic view of genetic association between SNPs at 11q23.3 and glioma risk in Chinese Han populations.</p

Association between the cumulative effect of four significant SNPs^a and the risk of glioma in a Chinese population.

<p>Bold characters indicate corresponding <i>P</i> values are less than 6.67×10⁻⁴.</p>a<p>Significant SNPs including s7115634, rs2236661, rs494560 and rs17748.</p>b<p>Adjusted for age and gender.</p

Lipid-Based Liquid Crystalline Nanoparticles Facilitate Cytosolic Delivery of siRNA via Structural Transformation

RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform thestructure in the intracellular acidic environment and perform high-efficient siRNA delivery for cancer treatment. The developed nano-Transformers have satisfactory siRNA loading efficiency and low cytotoxicity. Different from the traditional cationic nanocarriers, the endosomal membrane fusion induced by the conformational transition of lipids contributes to the easy dissociation of siRNA from nanocarriers and direct release of free siRNA into cytoplasm. We show that transfection with cyclin-dependent kinase 1 (CDK1)-siRNA-loaded nano-Transformers causes up to 95% reduction of relevant mRNA <i>in vitro</i> and greatly inhibits the tumor growth without causing any immunogenic response <i>in vivo</i>. This work highlights that the lipid-based nano-Transformers may become the next generation of siRNA delivery system with higher efficacy and improved safety profiles

LD plot of 11q23.3 using 15SNPs in 1024 ethnic Han Chinese controls.

<p>This plot was generated by the Haploview program with four Gamete Rule setting. Four blocks were determined. The rs number (top; from left to right) corresponds to the SNP name and the level of pairwise D’ indicates the degree of LD between the two SNPs.</p