GWAS follow-up study of esophageal squamous cell carcinoma identifies potential genetic loci associated with family history of upper gastrointestinal cancer.

Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P < 10-5 in the stage-1 meta-analysis of NCI and Henan GWAS data. In stage-2, the association for rs79747906 (located at 18p11.31, P = 5.79 × 10-6 in discovery) was replicated (P = 0.006), with a pooled-OR of 1.59 (95%CI: 1.11-2.28). We identified potential genetic variants associated with FH of UGI cancer. Our findings may provide important insights into new low-penetrance susceptibility regions involved in the susceptibility of families with multiple UGI cancer cases.

Association of genotypes of rs671 withinALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high- and low-incidence areas.

OBJECTIVE: : This study aimed to determine if gastric cardia adenocarcinoma (GCA) risk was associated with the lys (A or *2) allele at the rs671 (glu504lys) polymorphism within the aldehyde dehydrogenase 2 (ALDH2) gene in a Chinese Han population. We also aimed to investigateALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma (ESCC). METHODS: : We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and low-incidence areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used to genotype the rs671 polymorphism.χ2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA, and multivariate ordinal logistic regression was used to analyzeALDH2 genotypic distributions among different groups. RESULTS: : Compared withALDH2*1/*1 homozygotes,ALDH2*1/*2 andALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population (P>0.05). Interestingly, the ratio of homozygous or heterozygousALDH2 *2 carriers in high-incidence areas for both GCA and ESCC was lower than that in low-incidence areas (P<0.001). CONCLUSIONS: : Genotypes of rs671 atALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, theALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Designed synthesis of a series of zwitterion-polyoxometalate hybrid materials for selective scavenging and photolysis of dyes.

Zwitterions and polyoxometalates (POMs) are two kinds of functional moieties with very different properties for applications in different fields. We have developed an effective strategy to successfully immobilize these two different moieties into the frameworks of porous hybrid materials, in which the POM units act as templates and photoactive moieties. These hybrid materials demonstrate remarkable efficiency for selective scavenging and photolysis of cationic dyes from polluted water, and up to 10% dye uptake and quantitative photolysis of dyes have been realized.

Effects of vitexin on the pharmacokinetics and mRNA expression of CYP isozymes in rats.

In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), and midazolam (5 mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC-mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time reverse transcription-polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration-dependent and time-dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co-administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb-drug interactions.

Expanded organic building units for the construction of highly porous metal-organic frameworks.

Two new organic building units that contain dicarboxylate sites for their self-assembly with paddlewheel [Cu2(CO2)4] units have been successfully developed to construct two isoreticular porous metal-organic frameworks (MOFs), ZJU-35 and ZJU-36, which have the same tbo topologies (Reticular Chemistry Structure Resource (RCSR) symbol) as HKUST-1. Because the organic linkers in ZJU-35 and ZJU-36 are systematically enlarged, the pores in these two new porous MOFs vary from 10.8 Šin HKUST-1 to 14.4 Šin ZJU-35 and 16.5 Šin ZJU-36, thus leading to their higher porosities with Brunauer-Emmett-Teller (BET) surface areas of 2899 and 4014 m(2) g(-1) for ZJU-35 and ZJU-36, respectively. High-pressure gas-sorption isotherms indicate that both ZJU-35 and ZJU-36 can take up large amounts of CH4 and CO2, and are among the few porous MOFs with the highest volumetric storage of CH4 under 60 bar and CO2 under 30 bar at room temperature. Their potential for high-pressure swing adsorption (PSA) hydrogen purification was also preliminarily examined and compared with several reported MOFs, thus indicating the potential of ZJU-35 and ZJU-36 for this important application. Studies show that most of the highly porous MOFs that can volumetrically take up the greatest amount of CH4 under 60 bar and CO2 under 30 bar at room temperature are those self-assembled from organic tetra- and hexacarboxylates that contain m-benzenedicarboxylate units with the [Cu2(CO2)4] units, because this series of MOFs can have balanced porosities, suitable pores, and framework densities to optimize their volumetric gas storage. The realization of the two new organic building units for their construction of highly porous MOFs through their self-assembly with [Cu2(CO2)4] units has provided great promise for the exploration of a large number of new tetra- and hexacarboxylate organic linkers based on these new organic building units in which different aromatic backbones can be readily incorporated into the frameworks to tune their porosities, pore structures, and framework densities, thus targeting some even better performing MOFs for very high gas storage and efficient gas separation under high pressure and at room temperature in the near future.

Four metalloporphyrinic frameworks as heterogeneous catalysts for selective oxidation and aldol reaction.

Four porous metalloporphyrinic framework materials, [(CH3)2NH2][Zn2(HCOO)2(Mn(III)-TCPP)]·5DMF·2H2O (1; H6TCPP = tetrakis(4-carboxyphenyl)porphyrin), [(CH3)2NH2][Cd2(HCOO)2(Mn(III)-TCPP)]·5DMF·3H2O (2), [Zn2(HCOO)(Fe(III)(H2O)-TCPP)]·3DMF·H2O (3), and [Cd3(H2O)6(µ2-O)(Fe(III)-HTCPP)2]·5DMF (4) were synthesized by heating a mixture of M(III)Cl-H4TCPP (M = Mn and Fe) and M' (M' = Zn or Cd) nitrate in a mixed solvent of DMF and acetic acid. Compounds 1-3 are built up from M'2(COO)4 paddle-wheel subunits bridged by M(III)-TCPP and formate ligands to form their 3D connections. The formate pillar heterogeneously connects with M and M' cations in 1 and 2 and homogeneously joins M' cations in 3. The µ2-O bridged Fe(III)-HTCPP dimer performs as a decadentate ligand to link 10 cadmium cations for the formation of an interesting 3D coordination network of 4. The four porphyrinic frameworks present interesting catalytic properties in the selective epoxidation of olefins, oxidation of cyclohexane, and intermolecular aldol reaction of aldehydes and ketones.

Assembly and post-modification of a metal-organic nanotube for highly efficient catalysis.

A metal-organic nanotube (MONT) was synthesized by linking up the bent organic ligands and the tetra-coordinated zinc cations under mild conditions. Structural analysis revealed that the MONT has a very large exterior wall diameter of 4.91 nm and an interior channel diameter of 3.32 nm. Interlocking of the nanotubes gives rise to a 3D chiral framework containing 1D helical cylindered channels with diameter of 2.0 nm. The MONT has very interesting property by synergizing the functionality of nanotubes, metal-organic frameworks (MOFs), and N-heterocyclic carbenes (NHCs). The dye adsorption experiments demonstrate that the channels of the MONTs are accessible to large reagents typically used for catalysis. The postmodification of the MONT can be easily operated by unmarking the imidazolium moieties in the channel walls, which was conducted as a highly active heterogeneous catalyst for Suzuki-Miyaura and Heck coupling reactions, hydrogenation of olefins and nitrobenzene, while the constituent elements are less efficient for these reactions under the same conditions.

High expression of TGF-ß1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma.

This study evaluated the relationship between altered cytoplasmic expression of TGF-ß1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-ß1 expression at these locations. We found that TGF-ß1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.

Two metal-organic frameworks based on a double azolium derivative: post-modification and catalytic activity.

A new bifunctional N-heterocyclic carbene (NHC) precursor was used to construct two metal-organic frameworks, which can anchor palladium(II) sites by post-modification, presenting remarkable framework dependent catalytic activities.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.