Enhanced proton conductivity by guest molecule exchange in an acylamide-functionalized metal-organic framework.

Metal-organic frameworks (MOFs) as types of proton conductive materials have attracted much attention. Here, an acylamide-functionalized 3D MOF, [Ni3(TPBTC)2(stp)2(H2O)4]·2DMA·32H2O, has been successfully constructed via combining Ni(NO3)2, TPBTC (TPBTC = benzene-1,3,5-tricarboxylic acid tris-pyridin-4-ylamide) and 2-H2stp (2-H2stp = 2-sulfoterephthalic acid monosodium salt) under solvothermal conditions. Single-crystal X-ray diffraction revealed that there are uncoordinated guest DMA molecules in the pores of the compound. On removal of guest DMA molecules, the proton conductivity of the compound increased to 2.25 × 10-3 S cm-1 at 80 °C and 98% RH which is about 110 times that of the original material. It is hoped that this work can provide essential insight for designing and obtaining improved crystalline-state proton conducting materials by considering the influences of guest molecules on proton conduction properties of porous materials.

Three layered cucurbit[6]uril-based metal-organic rotaxane networks functionalized by sulfonic groups for proton conduction.

Three new cucurbit[6]uril (CB[6])-based metal-organic rotaxane networks (MORNs) (named CUST-711, CUST-712, and CUST-713) functionalized by a sulfonic group (-SO3H) have been designed and synthesized via a hydrothermal method. All three compounds exhibited similar two-dimensional (2D) wave layer structures. Their stability under different temperature and relative humidity conditions has been investigated and all the compounds showed excellent stability. Furthermore, their proton conduction properties were also discussed in detail. Due to different structures and sulfonic group sites, the three compounds exhibited different proton conduction abilities of which CUST-712 exhibited an intrinsic relatively high proton conductivity (1.75 × 10-4 S cm-1 at 85 °C and 97% relative humidity). These results provide ideas for the design and synthesis of functional CB[6]-based metal-organic rotaxane frameworks (MORFs) as proton conducting materials.

Syntheses of cucurbit[6]uril-based metal-organic rotaxane networks by the anion regulation strategy and their proton conduction properties.

Two new cucurbit[6]uril (CB[6])-based metal-organic rotaxane networks (MORNs) were successfully obtained by tuning the coordination sphere of metal copper clusters. Compounds 1 and 2 exhibited relatively high proton conductivity at 85 °C and 97% relative humidity (RH), providing great promise for fuel cell electrolyte materials.

Syntheses and magnetic properties of high-dimensional cucurbit[6]uril-based metal-organic rotaxane frameworks.

Three new high-dimensional cucurbit[6]-based metal-organic rotaxane frameworks [Co2(PR43)(BDC)2Cl2]·4H2O (1), [Co2(PR43)(BTC)2]·6H2O (2) and [Co2(PR43)(BPT)2]·20H2O (3) were obtained via the hydrothermal synthesis method. Compound 1 comprised a two-dimensional layered structure, while compounds 2 and 3 exhibited three-dimensional pillared structures. All the compounds showed good thermal stabilities. Furthermore, the magnetic properties of compounds 1-3 were also investigated in detail.

Effects of Brain Temperature on the Outcome of Patients with Traumatic Brain Injury: A Prospective Observational Study.

A prospective observational study collected temperature data from 51 patients in 11 neurosurgical centers and follow-up outcome information at 6 months in 49 patients. Brain temperature (Tbr) was measured directly by an intraventricular temperature sensor. Axillary temperature (Tax) and rectal temperature (Tre) were measured by electric thermometers. Tbr was 0.4 to 1.5°C higher than body temperature. Tre correlated well with the Tbr (coefficient: 0.7378; p < 0.05). Among all patients, Glasgow Coma Scale (GCS) scores on admission were significantly lower in the patients with post-operatively extreme peak temperature (Tpeak, < 37°C or >39°C in first 24 h) and major temperature variation (Tvari > 1°C in first 12 h; p < 0.05, p < 0.01, respectively). Among the patients with no temperature intervention, the extreme Tpeak group showed a lower Glasgow Outcome Scale-Extended (GOS-E) score at 6 months (p < 0.05) with lower GCS scores on admission (p < 0.01), compared with the moderate Tpeak group. Remarkably, the major Tvari group showed significantly lower GOS-E scores (p < 0.05) with the same GCS scores as the minor Tvari group. Thus, Tre is the better candidate to estimate Tbr. Spontaneously extreme Tpeak in TBI represents both more serious injury on admission and worse prognosis, and Tvari might be used as a novel prognostic parameter in TBI. Brain temperature is therefore one of the critical indicators evaluating injury severity, prognostication, and monitoring in the management of TBI. This prospective observational study has been registered in ClinicalTrials.gov ( https://clinicaltrials.gov ), and the registration number is NCT03068143.

Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study.

AIM: To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC). METHODS: Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone. RESULTS: The Kaplan-Meier survival analysis showed that the median overall survival (mOS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo (P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome (HFS), and hypertension (P < 0.05) than TACE treatment alone. CONCLUSION: Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the mOS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash (31.6%), HFS (39.5%) and hypertension (31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.

Guest exchange in a porous cucurbit[6]uril-based metal-organic rotaxane framework probed by NMR and X-ray crystallography.

The first CB[6]-based 3D porous metal-organic rotaxane framework is constructed by the reaction of CuCl2, terephthalic (H2BDC) and CB[6]-based [2]pseudorotaxanes ([PR44]2+·2[PF6]-) under solvothermal conditions. The structure of MORF-1 is a pillared-layer structure with 5-connected sqp topology, in which the effective free volume is 45.4% of the crystal volume. The guest molecules exchange in a single-crystal-to-single-crystal fashion, which was investigated using NMR spectroscopy and X-ray crystallography.

Hint1 suppresses migration and invasion of hepatocellular carcinoma cells in vitro by modulating girdin activity.

Histidine triad nucleotide-binding protein 1 (Hint1) is a haploinsufficient tumor suppressor gene. Its role in cancer cell migration has not been previously speculated. In the current study, we examined the expression of Hint1 in metastatic and non-metastatic lymph nodes of hepatocellular carcinoma (HCC) patients and further elucidated the effect of Hint1 expression on girdin expression and phosphorylation of AKT and ERK1/2 and on the migration of HCC cells in vitro. Expression of Hint1 and girdin in primary HCC tissues and metastatic and non-metastatic lymph nodes was determined by RT-PCR assays. HepG2 cells were transfected with plasmid vectors overexpressing Hint1 or small interfering RNA (siRNA) targeting Hint1, girdin, Hint1 plus girdin, or the scrambled RNA. Migration and invasion of HCC cells were examined by wound and Transwell assays. Protein expression was detected by immunofluorescence and immunoblotting assays. RT-PCR assays revealed that the messenger RNA (mRNA) transcript levels of Hint1 were markedly lower than those of primary HCC tissues and non-metastatic lymph nodes (P < 0.01). By contrast, the mRNA transcript levels of girdin were significantly higher than non-metastatic lymph nodes (P < 0.05). Furthermore, siRNA knockdown of HINT1 resulted in a significant increase in the mRNA transcript levels of girdin in HepG2 cells (P < 0.05). Wound assays and Transwell assays showed that Hint1 knockdown by siRNA significantly enhanced the migration and invasion of HepG2 cells compared to HepG2 cells transfected with scrambled siRNA. Hint1 knockdown also led to significantly increased phosphorylation of girdin and AKT in HepG2 cells (P < 0.05), which, however, was effectively aborted by girdin knockdown by siRNA (P < 0.05). Hint1 is downregulated in metastatic lymph nodes and is implicated in migration and invasion of HCC cells in vitro by modulating girdin and AKT expression and phosphorylation. The Hint1-girdin-AKT signaling axis should be further dissected for its role in HCC migration and invasion and may be therapeutically targeted to suppress tumor growth and metastasis.

A novel TP53 variant (rs78378222 A > C) in the polyadenylation signal is associated with increased cancer susceptibility: evidence from a meta-analysis.

Polymorphisms in TP53 are involved in the progression of different types of cancer. A rare novel TP53 variant (rs78378222 A > C allele) was found via whole-genome sequencing in 2011. This variant was shown to significantly increase the risk of glioma, colorectal adenoma and prostate cancer. Functional analysis further revealed that this variant hindered TP53 expression and its downstream effect on apoptosis. Several studies have investigated the relationship between rs78378222 and cancer susceptibility. However, the results were not consistent. We conducted the first meta-analysis to give a more credible assessment on the association about this variant and cancer risk. Our meta-analysis included 34 studies consisting of 36599 cases and 91272 controls. These studies were mostly on the basis of high-grade data from Genome-wide association studies (GWASs). The results indicated that TP53 rs78378222 was significantly associated with an increased risk of overall cancer (AC vs. AA: OR = 1.511, 95% CI = 1.285-1.777). Furthermore, stratified analyses indicated that rs78378222 increased the risk of nervous system cancer, skin cancer and other cancer. To summarize, this meta-analysis suggested that rs78378222 C allele is a potent risk factor for overall cancer.

Polyoxovanadate-based organic-inorganic hybrids: from {V5O9Cl} clusters to nanosized octahedral cages.

Three polyoxovanadate-based metal-organic polyhedra (denoted as VMOP-1, -2, and -3), adopting isostructural discrete octahedral cage geometries, were successfully synthesized under solvothermal conditions. These structures are all built up from the same pentavanadate {V5O9Cl} cluster connected by linear bidentate ligands (H2L1 = H2BDC, H2L2 = H2BDC-NH2, H2L3 = H2BDC-Br), respectively.

Interleukin-1B 31 C>T polymorphism combined with Helicobacter pylori-modified gastric cancer susceptibility: evidence from 37 studies.

Gastric cancer is one of the most common malignancies worldwide. Interleukin-1-beta (IL-1ß) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL-1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta-analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta-analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta-regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL-1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL-1B 31T variant in the population-based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03-1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL-1B 31 polymorphism increased gastric cancer risk in infection-positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02-1.78; heterozygous model: OR = 1.31, 95% CI = 1.04-1.66; recessive model: OR = 1.29, 95% CI = 1.04-1.61). The study suggested that IL-1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene-environment interaction in gastric carcinogenesis.

Spontaneous chiral resolution of a rare 3D self-penetration coordination polymer for sensitive aqueous-phase detection of picric acid.

Two unprecedented homochiral enantiomers based on two different kinds of rigid ligands, namely [Cd(NDC)L]2·H2O (1R and 1L), have been synthesized under hydrothermal conditions through spontaneous resolution. Their structures were determined by single-crystal X-ray diffraction analysis and further characterized by elemental analysis, IR, and thermogravimetric (TG) analysis. The resulting framework 1, constructed by four kinds of homo-handed helical chains represents the first 3D self-penetrating framework formed by decoration of single (10,3)-a net with helical chains. The single (10,3)-a net in 1 formed by three kinds of different homo-handed helical chains is different from the standard one, which should be ascribed to the usage of V-shaped ligand L. A unique self-penetration motif can be discovered in 1 where one helical chain alternately passes through 10-membered shortest circuits linked to each other and in contrary, the corresponding circuits are bound to the helical chain. Interestingly, 1 exhibits fluorescent emission in both the solid and solution phase. The uncoordinated nitrogen atom and amino group from the triazole core on the crystal surface make it suitable to detect picric acid in water. The luminescence intensity of 1 in water can be efficiently quenched by the addition of picric acid (PA). The sensitive detection of PA can be continuously performed for at least five cycles without diminishing the fluorescence intensity and destroying the framework structure of 1. The possible quenching mechanisms for PA are also investigated.

An organic-inorganic hybrid photocatalyst based on sandwich-type tetra-Co-substituted phosphotungstates with high visible light photocatalytic activity.

A novel 3D organic-inorganic hybrid framework constructed from tetra-Co(II)-substituted sandwich-type phosphotungstates with a rare 8-connected bcu topology is reported, which exhibited highly efficient photocatalysis activity under visible light and could be used for 5 cycles without any obvious decrease in activity.

Periodic tiling of triangular and square nanotubes in a cationic metal-organic framework for selective anion exchange.

A unique cationic metal-organic framework was synthesized by connecting the neutral rod-shaped secondary building unit with a cationic dicarboxylate ligand. This framework showed a rare snub square tessellation pattern by the periodic tiling of triangular and square nanotubes. The charge- and size-dependent ion-exchange of anion dyes was investigated.

The copper(I) metal azolate framework showing unusual coordination mode for the 1,2,4-triazole derivative and photocatalytic activity.

A unique three-dimensional metal azolate framework containing a tetranuclear copper cluster constructed by six 1,2,4-triazole units was synthesized in which the 1,2,4-triazole units show unusual bridging "crevice" coordination mode with their 1- and 2-positioned sp(2) N-atoms as symmetrically bridging centers. The photocatalytic activities of as-prepared compound were tested by degradation of rhodamine-B (RB) under different light irradiation.

Direct substitution of primary allylic amines with sulfinate salts.

The NH(2) group in primary allylic amines was substituted directly by sulfinate salts with excellent regio- and stereoselectivities. In the presence of 0.1 mol % [Pd(allyl)Cl](2), 0.4 mol % 1,4-bis(diphenylphosphino)butane (dppb), and excess boric acid, a range of α-unbranched primary allylic amines were smoothly substituted with sodium sulfinates in an α-selective fashion to give structurally diverse allylic sulfones in good to excellent yields with exclusive E selectivity. Replacing dppb with 1,1'-bi-2-naphthol (BINOL) allowed unsymmetric α-chiral primary allylic amines to be transformed into the corresponding allylic sulfones in good to excellent yields with excellent retention of ee. Importantly, the reaction complements known asymmetric methods in substrate scope via its unique ability to provide α-chiral allylic sulfones with high optical purity starting from unsymmetric allylic electrophiles.

Catalytic asymmetric cleavage of sp3 C-N bonds for access to highly enantioenriched N-benzylic sulfonamides.

In the presence of 10 mol% of a chiral phosphoric acid, a variety of racemic N-benzylic sulfonamides having N-(3-indolyl)methyl groups smoothly undergo kinetic resolution with benzyl thiol at 0 °C or at room temperature and the remaining sulfonamides are recovered in moderate to excellent yields and with excellent ee.

Inhibition of SIRT1 increases EZH2 protein level and enhances the repression of EZH2 on target gene expression.

OBJECTIVE: To study the regulatory rolesof SIRT1 on EZH2 expression and the further effects on EZH 2' s repression of target gene expression. METHODS: The stable SIRT1 RNAi and Control RNAi HeLa cells were established by infection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation(ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. RESULTS: Western blot results showed that EZH2 protein level increased upon SIRT1 depletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter regionof EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. CONCLUSIONS: Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expression.

Modulations of hMOF autoacetylation by SIRT1 regulate hMOF recruitment and activities on the chromatin.

A wide variety of nuclear regulators and enzymes are subjected to acetylation of the lysine residue, which regulates different aspects of protein functions. The MYST family histone acetyltransferase, human ortholog of MOF (hMOF), plays critical roles in transcription activation by acetylating nucleosomal H4K16. In this study, we found that hMOF acetylates itself in vitro and in vivo, and the acetylation is restricted to the conserved MYST domain (C2HC zinc finger and HAT), of which the K274 residue is the major autoacetylation site. Furthermore, the class III histone deacetylase SIRT1 was found to interact with the MYST domain of hMOF through the deacetylase catalytic region and deacetylate autoacetylated hMOF. In vitro binding assays showed that non-acetylated hMOF robustly binds to nucleosomes while acetylation decreases the binding ability. In HeLa cells, the recruitment of hMOF to the chromatin increases in response to SIRT1 overexpression and decreases after knockdown of SIRT1. The acetylation mimic mutation K274Q apparently decreases the chromatin recruitment of hMOF as well as the global H4K16Ac level in HeLa cells. Finally, upon SIRT1 knockdown, hMOF recruitment to the gene body region of its target gene HoxA9 decreases, accompanied with decrease of H4K16Ac at the same region and repression of HoxA9 transcription. These results suggest a dynamic interplay between SIRT1 and hMOF in regulating H4K16 acetylation.

Epigenetic repression of SATB1 by polycomb group protein EZH2 in epithelial cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the regulatory mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1.</p><p><b>METHODS</b>HeLa epithelial cells were treated with either histone deacetylase inhibitor (HDACi) trichostatin A (TSA) or DNA methylation inhibitor 5-Aza-C before detecting SATB1 expression. Luciferase reporter system was applied to measure effects of EZH2 on SATB1 promoter activity. Over-expression or knockdown of EZH2 and subsequent quantitative reverse transcription-polymerase chain reaction were performed to determine the effect of this Polycomb group protein on SATB1 transcription. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of EZH2 and trimethylated H3K27 (H3K27me3) at SATB1 promoter in HeLa cells. K562 cells and Jurkat cells, both having high-level expression of SATB1, were used in the ChIP experiment as controls.</p><p><b>RESULTS</b>Both TSA and 5-Aza-C increased SATB1 expression in HeLa cells. Over-expression of EZH2 reduced promoter activity as well as the mRNA level of SATB1, while knockdown of EZH2 apparently enhanced SATB1 expression in HeLa cells but not in K562 cells and Jurkat cells. ChIP assay Results suggested that epigenetic silencing of SATB1 by EZH2 in HeLa cells was mediated by trimethylation modification of H3K27. In contrast, enrichment of EZH2 and H3K27me3 was not detected within proximal promoter region of SATB1 in either K562 or Jurkat cells.</p><p><b>CONCLUSION</b>SATB1 is a bona fide EZH2 target gene in HeLa cells and the repression of SATB1 by EZH2 may be mediated by trimethylation modification on H3K27.</p>