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The compounds MNi21B20 (M = In, Sn) have been synthesized and their cubic crystal structure determined (space group Pm3̅m, lattice parameters a = 7.1730(1) Å and a = 7.1834(1) Å, respectively). The structure can be described as a hierarchical partitioning of space based on a reo-e net formed by Ni3 species with large cubical, cuboctahedral and rhombicuboctahedral voids being filled according to [Ni1@Ni38], [M@Ni312], and [Ni26@B20@Ni324], respectively. The [Ni6@B20] motif inside the rhombicuboctahedral voids features an empty [Ni6] octahedron surrounded by a [B20] cage recently described in E2Ni21B20 (E = Zn, Ga). Position-space bonding analysis using ELI-D and QTAIM space partitioning as well as 2- and 3-center delocalization indices gives strong support to an alternative chemical description of space partitioning based on face-condensed [B@Ni6] trigonal prisms as basic building blocks. The shortest B–B contacts display locally nested 3-center B–B–Ni bonding inside each trigonal prism. This clearly rules out the notion of [Ni6@B20] clusters and leads to the arrangement of 20 face-condensed [B@Ni23Ni33] trigonal prisms resulting in a triple-shell like situation Ni26@B20@Ni324(reo-e), where the shells display comparable intra- and inter-shell bonding. Both compounds are Pauli paramagnets displaying metallic conductivity. [ABSTRACT FROM AUTHOR]

Abstract: A comparative study of phase components and compositions was performed for the pressureless sintered HfB2–SiC–WC composites by various analytical methods. The relative decrease of HfB2 phase leads to a new reaction of HfO2 removal by WC to create B2O3. By using SiC instead of Si3N4 as milling medium, the WB phase was suppressed to the trace level while the W solid-solution in HfB2 phase was favored. The W solution in both the primary HfB2 and resultant HfC phases indicates that the WC additive was involved throughout the sintering process by dissolving into sintering liquid, which remains at the intergranular regions to form amorphous oxides as well as trace W-rich phases. This is effectively a reactive liquid-phase sintering to realize the reaction, solid-solution and densification collectively to achieve a designable HfB2–SiC–HfC composite by pressureless sintering, which may also be extended to other sintering methods. [Copyright &y& Elsevier]

Abstract: Objective: We investigated the linkage between SNPs in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1, and explored the effect of linked polymorphism on the absorption of talinolol after a single oral dose of 100 mg. Methods: The genotype of 192 healthy Chinese volunteers was determined using PCR-RFLP with respect to the MDR1 alleles of interest, C1236T, G2677T/A and C3435T. Linkage disequilibrium was analyzed using PHASE software. Consecutive eligible subjects received a single oral dose of 100 mg talinolol. Venous blood samples were taken at intervals up to 60 h post dose for HPLC analysis of plasma concentration of talinolol to obtain a pharmacokinetic profile. Results: Linkage disequilibrium existed between exon 21 (G2677T/A) and exon 26 (C3435T), exon 12 (C1236T) and exon 21 (G2677T/A), but not between exon 12 (C1236T) and exon 21 (G2677T/A). AUC (0,3h), AUC (0,∞), C max and C max/AUC (0,∞), used as indices of talinolol absorption, were not significantly different between the genotype groups of 2677GG/3435TT, 2677TT/3435TT, 2677GT/3435CT and 2677AT/3435CT. For these 4 groups, AUC(0,3h) were 436.8±50.1, 510.1±86.3, 466.1±77.8 and 437.2±73.4 (μg×h/l) and the C max/AUC (0,∞) were 0.097±0.018, 0.093±0.022, 0.105±0.014 and 0.102±0.027 (h−1), respectively. (P >0.05). Conclusions: The linked MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T apparently did not contribute to the absorptive pharmacokinetics of a single oral dose of 100 mg talinolol. [Copyright &y& Elsevier]

The compounds MNi 21 B 20 (M = In, Sn) have been synthesized and their cubic crystal structure determined (space group Pm3[combining macron]m, lattice parameters a = 7.1730(1) Å and a = 7.1834(1) Å, respectively). The structure can be described as a hierarchical partitioning of space based on a reo-e net formed by Ni3 species with large cubical, cuboctahedral and rhombicuboctahedral voids being filled according to [Ni1@Ni3 8 ], [M@Ni3 12 ], and [Ni2 6 @B 20 @Ni3 24 ], respectively. The [Ni 6 @B 20 ] motif inside the rhombicuboctahedral voids features an empty [Ni 6 ] octahedron surrounded by a [B 20 ] cage recently described in E 2 Ni 21 B 20 (E = Zn, Ga). Position-space bonding analysis using ELI-D and QTAIM space partitioning as well as 2- and 3-center delocalization indices gives strong support to an alternative chemical description of space partitioning based on face-condensed [B@Ni 6 ] trigonal prisms as basic building blocks. The shortest B-B contacts display locally nested 3-center B-B-Ni bonding inside each trigonal prism. This clearly rules out the notion of [Ni 6 @B 20 ] clusters and leads to the arrangement of 20 face-condensed [B@Ni2 3 Ni3 3 ] trigonal prisms resulting in a triple-shell like situation Ni2 6 @B 20 @Ni3 24 (reo-e), where the shells display comparable intra- and inter-shell bonding. Both compounds are Pauli paramagnets displaying metallic conductivity.

Niemann-Pick C1-like 1 (NPC1L1i) protein is the key transporter responsible for dietary cholesterol absorption. Recent studies indicated that several functional polymorphisms of NPC1L1 were associated with coronary heart disease (CHD) and response to ezetimibe therapy. The aim of the present study was to analyze the allele frequency and haplotype distribution of NPC1L1 polymorphisms in Chinese Hans and to compare them with those of other ethnic populations reported before. Blood samples were collected from 424 unrelated Chinese Hans (246 males and 178 females). Ten NPC1L1 polymorphisms (-762T > C, -133A > G, -18C > A, 1721C > T, 1735C > G, 1764T > C, 1767G > A, 27677T > C, 25342A > C and 28650A > G) were genotyped by direct sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Among the variants, the minor allele frequency of -762T > C and 1735C > G were 35.0% and 37.0%, respectively. Furthermore, these two polymorphisms were highly linked with a D' value of 0.80. The observed frequencies of two major haplotypes were 59.1% for T-762/C1735 and 30.1% for C-762/G1735, respectively. The frequencies of the rest variants were extremely low (1.8% for - 133G, 1.5% for -18A, 0.9% for 1721T and only 0.2% for 27677C allele, respectively) or even not detected (1764T > C, 1767G > A, 25342A > C and 28650A > G) in our study population. Comparison with other ethnic populations revealed a remarkable genetic variability in the incidences of NPC1L1 polymorphisms. The frequencies of NPC1L1 polymorphisms in Chinese Hans are comparable to Japanese population but totally different from Caucasians, African-Americans and Hispanic individuals. This is the first study to report the ethnic difference in the frequencies of NPC1L1 functional polymorphisms in detail. -762T > C and 1735C > G are two prevalent NPC1L1 variants which need further studies to explore their clinical impact on CHD prevalence and response to ezetimibe therapy in Chinese Hans.

This study was designed to investigate the potential association between NTCP c.800C >T polymorphism and rosuvastatin pharmacokinetics in Chinese healthy males. 305 individuals were enrolled to identify NTCP c.800C > T, OATP1B1 c.521T > C and BCRP c.421C > A genotypes by direct sequencing and pyrosequencing methods, respectively. 17 healthy volunteers who were OATP1B1 c.521TT and BCRP c.421CC wild-type homozygotes with different NTCP c.800C > T genotype were selected to participate in this pharmacokinetic study. Nine were NTCP c.800CC wild-type homozygotes and the other eight subjects were carriers with at least one c.800T variant allele (seven subjects with c.800CT genotype and one was homozygote of c.800TT). All the subjects received a single oral dose of 10 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured up to 72 h by a LC-MS method. NTCP c.800C > T genetic polymorphism markedly effected rosuvastatin pharmacokinetics. The AUC(o-72) and AUC(0 --> ∞) in subjects with NTCP c.800CT + TT genotype were 56% (162.64 ± 37.55 vs. 103.99 ± 28.15 ng x h/ml, P = 0.016) and 57% greater (178.51 ± 42.75 vs. 113.60 ± 33.73 ng x h/ml, P = 0.020) than those in the c.800CC wild-type subjects, respectively. In the c.800CT + TT mutant group, the C(max) was about 78% higher than those in c.800CC genotype (14.31 ± 3.63 vs. 8.04 ± 1.72 ng x h/ml, P = 0.004). The oral clearance (CL/F) of rosuvastatin in subjects with the c.800CT+TT genotype was only 63% of those in the c.800CC genotype (58.32 ± 12.16 vs. 93.04 ± 20.61 ng x h/ml, P = 0.009). The half-time (T1/2) and the T(max) had no significant difference between two groups (p = 0.466 and 0.713, respectively). NTCP c.800C > T polymorphism play a critical role in the individual variability of rosuvastatin pharmacokinetics in Chinese healthy males after excluding the impact of OATP1B1 c.521T > C and BCRP c.421C > A polymorphisms.