Metal-Organic Framework with Space-Partition Pores by Fluorinated Anions for Benchmark C2H2/CO2 Separation.

The efficient separation of C2H2 from C2H2/CO2 or C2H2/CO2/CH4 mixtures is crucial for achieving high-purity C2H2 (>99%), essential in producing contemporary commodity chemicals. In this report, we present ZNU-12, a metal-organic framework with space-partitioned pores formed by inorganic fluorinated anions, for highly efficient C2H2/CO2 and C2H2/CO2/CH4 separation. The framework, partitioned by fluorinated SiF62- anions into three distinct cages, enables both a high C2H2 capacity (176.5 cm3/g at 298 K and 1.0 bar) and outstanding C2H2 selectivity over CO2 (13.4) and CH4 (233.5) simultaneously. Notably, we achieve a record-high C2H2 productivity (132.7, 105.9, 98.8, and 80.0 L/kg with 99.5% purity) from C2H2/CO2 (v/v = 50/50) and C2H2/CO2/CH4 (v/v = 1/1/1, 1/1/2, or 1/1/8) mixtures through a cycle of adsorption-desorption breakthrough experiments with high recovery rates. Theoretical calculations suggest the presence of potent "2 + 2" collaborative hydrogen bonds between C2H2 and two hexafluorosilicate (SiF62-) anions in the confined cavities.

A novel hydrophobic carborane-hybrid microporous material for reversed C2H6 adsorption and efficient C2H4/C2H6 separation under humid conditions.

Since ethylene (C2H4) is important feedstock in the chemical industry, developing economical and energy-efficient adsorption separation techniques based on ethane (C2H6)-selective adsorbents to replace the energy-intensive cryogenic distillation is highly demanded, which however remains a daunting challenge. While previous anionic boron cluster hybrid microporous materials display C2H4-selective features, we herein reported that the incorporation of a neutral para-carborane backbone and aliphatic 1,4-diazabicyclo[2.2.2]octane (DABCO) enables the reversed adsorption of C2H6 over C2H4. The generated carborane-hybrid microporous material ZNU-10 (ZNU = Zhejiang Normal University) is highly stable in humid air and maintains good C2H6/C2H4 separation performance under high humidity. Gas loaded single crystal structure and density-functional theory (DFT) calculations revealed that the weakly polarized carborane and DABCO within ZNU-10 induce more specific C-Hδ+⋯Hδ--B dihydrogen bonds and other van der Waals interactions with C2H6, while the suitable pore space allows the high C2H6 uptake. Approximately 14.5 L kg-1 of polymer grade C2H4 can be produced from simulated C2H6/C2H4 (v/v 10/90) mixtures under ambient conditions in a single step, comparable to those of many popular materials.

Specific Propyne Trapping Sites within a Robust MOF for Efficient Propyne/Propadiene Separation with Record Propadiene Productivity.

Separating propyne/propadiene to produce pure propadiene is extremely challenging in industry due to their similar properties. Herein, a novel ZrF6 2- anion pillared cage-like metal-organic framework (termed as CuZrF6 -TPA) for highly efficient propyne/propadiene separation is reported. It exhibits high propyne capacity (177.4/188.6 cm3 /cm3 at 0.5/1.0 bar and 298 K), benchmark separation selectivity (6.0), and remarkable separation potential (5.7 mol L-1 ) simultaneously. Record propadiene productivity (≈4.7 mol L-1 ) is achieved through a single adsorption process in breakthrough experiments with excellent recycle stability even under humid conditions. Based on the structure of propyne-loaded single crystals, two binding sites are identified, including a major propyne trapping site at the windows and a minor binding site located in the large cages. Modelling studies further confirm that the contracted cage windows surrounded with rotating Lewis basic F atoms and aromatic rings are the optimal bonding sites to capture propyne with multiple hydrogen bonding and π···π interactions.

Topological Design of Unprecedented Metal-Organic Frameworks Featuring Multiple Anion Functionalities and Hierarchical Porosity for Benchmark Acetylene Separation.

Separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) or ethylene (C2 H4 ) is industrially important but still challenging so far. Herein, we developed two novel robust metal organic frameworks AlFSIX-Cu-TPBDA (ZNU-8) with znv topology and SIFSIX-Cu-TPBDA (ZNU-9) with wly topology for efficient capture of C2 H2 from CO2 and C2 H4 . Both ZNU-8 and ZNU-9 feature multiple anion functionalities and hierarchical porosity. Notably, ZNU-9 with more anionic binding sites and three distinct cages displays both an extremely large C2 H2 capacity (7.94 mmol/g) and a high C2 H2 /CO2 (10.3) or C2 H2 /C2 H4 (11.6) selectivity. The calculated capacity of C2 H2 per anion (4.94 mol/mol at 1 bar) is the highest among all the anion pillared metal organic frameworks. Theoretical calculation indicated that the strong cooperative hydrogen bonds exist between acetylene and the pillared SiF6 2- anions in the confined cavity, which is further confirmed by in situ IR spectra. The practical separation performance was explicitly demonstrated by dynamic breakthrough experiments with equimolar C2 H2 /CO2 mixtures and 1/99 C2 H2 /C2 H4 mixtures under various conditions with excellent recyclability and benchmark productivity of pure C2 H2 (5.13 mmol/g) or C2 H4 (48.57 mmol/g).

Insights into the thermodynamic-kinetic synergistic separation of propyne/propylene in anion pillared cage MOFs with entropy-enthalpy balanced adsorption sites.

Propyne/propylene (C3H4/C3H6) separation is an important industrial process yet challenged by the trade-off of selectivity and capacity due to the molecular similarity. Herein, record C3H4/C3H6 separation performance is achieved by fine tuning the pore structure in anion pillared MOFs. SIFSIX-Cu-TPA (ZNU-2-Si) displays a benchmark C3H4 capacity (106/188 cm3 g-1 at 0.01/1 bar and 298 K), excellent C3H4/C3H6 IAST selectivity (14.6-19.3) and kinetic selectivity, and record high C3H4/C3H6 (10/90) separation potential (36.2 mol kg-1). The practical C3H4/C3H6 separation performance is fully demonstrated by breakthroughs under various conditions. 37.8 and 52.9 mol kg-1 of polymer grade C3H6 can be produced from 10/90 and 1/99 C3H4/C3H6 mixtures. 4.7 mol kg-1 of >99% purity C3H4 can be recovered by a stepped desorption process. Based on the in situ single crystal analysis and DFT calculation, an unprecedented entropy-enthalpy balanced adsorption pathway is discovered. MD simulation further confirmed the thermodynamic-kinetic synergistic separation of C3H4/C3H6 in ZNU-2-Si.

Benchmark single-step ethylene purification from ternary mixtures by a customized fluorinated anion-embedded MOF.

Ethylene (C2H4) purification from multi-component mixtures by physical adsorption is a great challenge in the chemical industry. Herein, we report a GeF62- anion embedded MOF (ZNU-6) with customized pore structure and pore chemistry for benchmark one-step C2H4 recovery from C2H2 and CO2. ZNU-6 exhibits significantly high C2H2 (1.53 mmol/g) and CO2 (1.46 mmol/g) capacity at 0.01 bar. Record high C2H4 productivity is achieved from C2H2/CO2/C2H4 mixtures in a single adsorption process under various conditions. The separation performance is retained over multiple cycles and under humid conditions. The potential gas binding sites are investigated by density functional theory (DFT) calculations, which suggest that C2H2 and CO2 are preferably adsorbed in the interlaced narrow channel with high aff0inity. In-situ single crystal structures with the dose of C2H2, CO2 or C2H4 further reveal the realistic host-guest interactions. Notably, rare C2H2 clusters are formed in the narrow channel while two distinct CO2 adsorption locations are observed in the narrow channel and the large cavity with a ratio of 1:2, which accurately account for the distinct adsorption heat curves.

High-altitude exposure decreases bone mineral density and its relationship with gut microbiota: Results from the China multi-ethnic cohort (CMEC) study.

BACKGROUND: Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship. METHODS: A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography-mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the "altitude-QUI" analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the "altitude-microbiota-QUI" analysis. Multivariate linear regression models and mediation analyses were conducted among participants. RESULTS: A significant negative association between high-altitude and QUI was obtained (mean difference = -0.373 standard deviation [SD], 95% confidence interval [CI]: -0.389, -0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = -0.185 SD, 95%CI: -0.360, -0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05). CONCLUSION: High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density.

Comprehensive Pore Tuning in an Ultrastable Fluorinated Anion Cross-Linked Cage-Like MOF for Simultaneous Benchmark Propyne Recovery and Propylene Purification.

Propyne/propylene (C3 H4 /C3 H6 ) separation is an important but challenging industrial process to produce polymer-grade C3 H6 and recover high-purity C3 H4 . Herein, we report an ultrastable TiF6 2- anion cross-linked metal-organic framework (ZNU-2) with precisely controlled pore size, shape and functionality for benchmark C3 H4 storage (3.9/7.7 mmol g-1 at 0.01/1.0 bar and 298 K) and record high C3 H4 /C3 H6 (10/90) separation potential (31.0 mol kg-1 ). The remarkable C3 H4 /C3 H6 (1/99, 10/90, 50/50) separation performance was fully demonstrated by simulated and experimental breakthroughs under various conditions with excellent recyclability and high productivity (42 mol kg-1 ) of polymer-grade C3 H6 from a 1/99 C3 H4 /C3 H6 mixture. A modelling study revealed that the symmetrical spatial distribution of six TiF6 2- on the icosahedral cage surface provides two distinct binding sites for C3 H4 adsorption: one serves as a tailored single C3 H4 molecule trap and the other boosts C3 H4 accommodation by cooperative host-guest and guest-guest interactions.

Gram-Scale Synthesis of an Ultrastable Microporous Metal-Organic Framework for Efficient Adsorptive Separation of C2H2/CO2 and C2H2/CH4.

A highly water and thermally stable metal-organic framework (MOF) Zn2(Pydc)(Ata)2 (1, H2Pydc = 3,5-pyridinedicarboxylic acid; HAta = 3-amino-1,2,4-triazole) was synthesized on a large scale using inexpensive commercially available ligands for efficient separation of C2H2 from CH4 and CO2. Compound 1 could take up 47.2 mL/g of C2H2 under ambient conditions but only 33.0 mL/g of CO2 and 19.1 mL/g of CH4. The calculated ideal absorbed solution theory (IAST) selectivities for equimolar C2H2/CO2 and C2H2/CH4 were 5.1 and 21.5, respectively, comparable to those many popular MOFs. The Qst values for C2H2, CO2, and CH4 at a near-zero loading in 1 were 43.1, 32.1, and 22.5 kJ mol-1, respectively. The practical separation performance for C2H2/CO2 mixtures was further confirmed by column breakthrough experiments.

Interpenetration Symmetry Control Within Ultramicroporous Robust Boron Cluster Hybrid MOFs for Benchmark Purification of Acetylene from Carbon Dioxide.

The separation of C2 H2 /CO2 is an important process in industry but challenged by the trade-off of capacity and selectivity owning to their similar physical properties and identical kinetic molecular size. We report the first example of symmetrically interpenetrated dodecaborate pillared MOF, ZNU-1, for benchmark selective separation of C2 H2 from CO2 with a high C2 H2 capacity of 76.3 cm3 g-1 and record C2 H2 /CO2 selectivity of 56.6 (298 K, 1 bar) among all the robust porous materials without open metal sites. Single crystal structure analysis and modeling indicated that the interpenetration shifting from asymmetric to symmetric mode provided optimal pore chemistry with ideal synergistic "2+2" dihydrogen bonding sites for tight C2 H2 trapping. The exceptional separation performance was further evidenced by simulated and experimental breakthroughs with excellent recyclability and high productivity (2.4 mol kg-1 ) of 99.5 % purity C2 H2 during stepped desorption process.

Rational Design of Microporous MOFs with Anionic Boron Cluster Functionality and Cooperative Dihydrogen Binding Sites for Highly Selective Capture of Acetylene.

Separation of acetylene (C2 H2 ) from carbon dioxide (CO2 ) or ethylene (C2 H4 ) is important in industry but limited by the low capacity and selectivity owing to their similar molecular sizes and physical properties. Herein, we report two novel dodecaborate-hybrid metal-organic frameworks, MB12 H12 (dpb)2 (termed as BSF-3 and BSF-3-Co for M=Cu and Co), for highly selective capture of C2 H2 . The high C2 H2 capacity and remarkable C2 H2 /CO2 selectivity resulted from the unique anionic boron cluster functionality as well as the suitable pore size with cooperative proton-hydride dihydrogen bonding sites (B-Hδ- ⋅⋅⋅Hδ+ -C≡C-Hδ+ ⋅⋅⋅Hδ- -B). This new type of C2 H2 -specific functional sites represents a fresh paradigm distinct from those in previous leading materials based on open metal sites, strong electrostatics, or hydrogen bonding.

A Microporous Metal-Organic Framework Supramolecularly Assembled from a CuII Dodecaborate Cluster Complex for Selective Gas Separation.

A novel 3D metal-organic framework BSF-1 based on the closo-dodecaborate cluster [B12 H12 ]2- was readily prepared at room temperature by supramolecular assembly of CuB12 H12 and 1,2-bis(4-pyridyl)acetylene. The permanent microporous structure was studied by X-ray crystallography, powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and gas sorption. The experimental and theoretical study of the gas sorption behavior of BSF-1 for N2 , C2 H2 , C2 H4 , CO2 , C3 H8 , C2 H6 , and CH4 indicated excellent separation selectivities for C3 H8 /CH4 , C2 H6 /CH4 , and C2 H2 /CH4 as well as moderately high separation selectivities for C2 H2 /C2 H4 , C2 H2 /CO2 , and CO2 /CH4 . Moreover, the practical separation performance of C3 H8 /CH4 and C2 H6 /CH4 was confirmed by dynamic breakthrough experiments. The good cyclability and high water/thermal stability render it suitable for real industrial applications.

Expression, purification, and in vitro mitochondrial interaction analysis of full-length and truncated human tumor suppresser p53.

p53 is a potent tumor suppressor which can prevent the propagation of cells carrying oncogenic lesions via a multitude of pathways. Besides the transactivation of downstream genes encoding proapoptotic proteins, p53 is also able to physically interact with mitochondria and induce apoptosis through a so called transcriptional-independent pathway. In this study, we described a quick method for the expression and purification of soluble recombinant p53 and its different truncations in E. coli. These proteins are able to interact with mitochondria and induce mitochondrial outer membrane permeabilization and associated downstream apoptotic events in a cell-free apoptosis analysis system.

RhIII -Catalyzed Functionalization of closo-Dodecaborates by Selective B-H Activation: Bypassing Competitive C-H Activation.

The closo-dodecaborate dianion is a fundamental icosahedral boron cage with 12 identical B-H vertices. The chemistry and applications of boron clusters have inspired researchers ever since their discovery several decades ago, and the selective modification of the cage positions has remained a major synthetic challenge. A rhodium(III)-catalyzed B-H functionalization-cyclization cascade of closo-dodecaborate amides is reported. The transformations occur chemoselectively at B-H positions in the presence of C-H bonds prone to competitive cyclometalation. Previously inaccessible cage derivatives with B-C(sp2 ) and B-C(sp3 ) bonds as well as a fused diboraoxazole ring are obtained in a one-pot process. The reactions proceed under mild conditions and exhibit complete cage regioselectivity with broad functional group tolerance. These cluster derivatives enable a largely extended investigation of the application of anionic boron clusters in research areas such as photoluminescent materials and medicinal chemistry.

The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53-binding site of the p21 gene in response to doxorubicin.

Transcriptional activation of p21 (cyclin-dependent kinase inhibitor 1A) due to DNA damage often alters the distribution of histone variant H2A.Z at the p21 gene. However, whether the human INO80 complex regulates changes in H2A.Z at the p21 promoter is unclear. We show here that activation of p21 expression by doxorubicin (Doxo) in U2OS cells is required for removal of H2A.Z by INO80 at the p53-binding site proximal region (-2.2 kb) of the p21 promoter. A purified INO80 complex, but not the INO80E653Q mutant-complex, which lost DNA-sliding activity, is mainly responsible for removing H2A.Z from reconstituted nucleosomes in vitro. This activity was enhanced with MOF-mediated histone acetylation, suggesting that INO80 more readily removes H2A.Z from loosened nucleosomes. Also, co-occupancy of INO80 and H2A.Z -2.2 kb upstream of the p21 transcriptional start site (TSS) was observed. H2A.Z at this region was removed in a short time after Doxo treatment and activated p21 expression. However, p21 induction was inhibited by INO80 knockdown by delaying H2A.Z removal, indicating the need for INO80. Moreover, shMOF-mediated histone acetylation reduced recruitment of INO80 -2.2 kb upstream of p21 TSS and inhibited the removal of H2A.Z in Doxo-treated cells. These data provide new insights into the transcriptional regulation of p21 by the INO80 complex.

BCCIP binds to and activates its promoter in a YY1-dependent fashion in HCT116 cells.

The restriction of Yin Yang 1 (YY1) at BRCA2 and CDKN1A/p21-interacting protein (BCCIP) transcriptional start site (TSS) proximal region in several human cancer cell lines was found by analyzation of ChIP-Seq database from UCSC Genome Browser (http://genome.ucsc.edu). However, whether the stabilization of YY1 by BCCIP impacts its recruitment in the BCCIP promoter region is unclear. Here, we present evidence that transcriptional regulation of YY1 on BCCIP is closely related to YY1 stability in HCT116 human colon cancer cells. YY1 stabilization was in turn regulated by BCCIP, suggesting the existence of a BCCIP-YY1 feedback loop in regulating BCCIP transcription by the YY1. Overexpression of BCCIP stabilized YY1 while knockdown of BCCIP reduced YY1 protein level. In addition, direct interaction between YY1 and BCCIP was confirmed by coimmunoprecipitation approach. Also, the N-terminus region of BCCIP, including the internal conserved domain (ICD), was responsible for binding with the amino acid 146-270 of YY1. More importantly, YY1 stability was related to the BCCIP/ICD domain-mediated YY1 ubiquitination pathway. Moreover, a limited BCCIP promoter region containing YY1 binding site (CCGCCATC) was tightly associated with the pGL4-BCCIP-Luc luciferase activity. In ChIP assays, shBCCIP lentiviral-mediated YY1 instability decreased recruitment of the YY1 at BCCIP TSS proximal region, which could not be restored by YY1 overexpression. Furthermore, knockdown of YY1 inhibited the binding of BCCIP itself at BCCIP promoter region proximal to TSS, demonstrating that transcriptional regulation of the YY1 on BCCIP can be modulated by BCCIP itself in a YY1-dependent fashion.

O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3.

The human males absent on the first (MOF)-containing histone acetyltransferase nonspecific lethal (NSL) complex comprises nine subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase, isoform 1 (OGT1). However, whether the O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remain unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3. Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8. Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex. Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3. In addition, wheat germ agglutinin affinity purification verified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O-GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3. This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1C964A, that lacks O-GlcNAc transferase activity. Furthermore, stabilization of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4 Lys-5, Lys-8, and Lys-16 in cells. These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3.

Restoration of the tumor-suppressor function to mutant p53 by Ganoderma lucidum polysaccharides in colorectal cancer cells.

Ganoderma lucidum polysaccharides (GLPs), isolated from spores, mycelia and fruiting bodies of Ganoderma lucidum, have been suggested to possess anticancer activities in a large number of basic studies. A recent survey revealed that GLP-induced inhibition of cancer cell growth was dependent on the existence of functional p53. However, the actual role of p53-mediated tumor-suppressing pathways in facilitating the anticancer effect of GLPs is still unclear. In the present study, we investigated the interaction between GLPs and mutant p53 that exists in more than half of the known types of cancers. Our results showed that GLPs reactivated mutant p53 in colorectal cancer HT29 (p53R273H) and SW480 (p53R273H&P309S) cells while applied alone or together with 5-fluorouracil (5-FU). This reactivation further induced cell growth inhibition and apoptosis. In addition, western blot assay and in vitro cell-free apoptosis assay suggested that the activation of mutant p53 was effective in both a transcriptional-dependent and -independent pathway. Altogether, our data demonstrated for the first time that GLPs show prominent anticancer activities by reactivating several types of mutant p53. Therefore, targeting mutant p53 by GLPs alongside other chemotherapeutics may be considered as a novel treatment strategy for cancer.

Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability.

We previously identified an ATP-dependent human Ino80 (INO80) chromatin remodeling complex which shares a set of core subunits with yeast Ino80 complex. Although research evidence has suggested that INO80 complex functions in gene transcription and genome stability, the precise mechanism remains unclear. Herein, based on gene expression profiles from the INO80 complex-knockdown in HeLa cells, we first demonstrate that INO80 complex negatively regulates the p21Waf1/Cip1 (p21) expression in a p53-mediated mechanism. In chromatin immunoprecipitation (ChIP) and a sequential ChIP (Re-ChIP) assays, we determined that the INO80 complex and p53 can bind to the same promoter region of p21 gene (-2.2 kb and -1.0 kb upstream of the p21 promoter region), and p53 is required for the recruitment of the INO80 complex to the p21 promoter. RNAi knockdown strategies of INO80 not only led to prolonged progression of cell cycle phase G2/M to G1, but it also resulted in abnormal chromosome stability. Interestingly, high expression of p21 was observed in most morphologically-changed cells, suggesting that negative regulation of p21 by INO80 complex might be implicated in maintaining the cell cycle process and chromosome stability. Together, our findings will provide a theoretical basis to further elucidate the cellular mechanisms of the INO80 complex.