Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40–50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.</p

Ultrafastly Interweaving Graphdiyne Nanochain on Arbitrary Substrates and Its Performance as a Supercapacitor Electrode

A moderate method is first developed here for superfast (in seconds) growth of an ultrafine graphdiyne (GDY) nanochain on arbitrary substrates in the atmosphere. This is an environmentally friendly and metal-catalyst-free method, efficiently eliminating extraneous contaminations for the carbon materials. The seamless GDY coating on any substrates demonstrates that an all-carbon GDY possesses outstanding controllability and processability, perfectly compensating for the drawbacks of prevailing all-carbon materials. After the decoration of 3D GDY nanostructures, the substrates become superhydrophobic with contact angles high up to of 148° and can be used as outstanding frameworks for storing organic pollution. Because of the reasonable porous and 3D continuous features, the as-prepared samples can be applied as high-performance binder-free supercapacitor electrodes with high area capacitance of up to 53.66 mF cm ^–2, prominent power performance, and robust long-term retention (99% after 1300 cycles)

Solvent Effects on Hydride Transfer from Cp*(P-P)FeH to BNA⁺ Cation

Examining of the hydride transfer reaction between Cp*­(Ph₂PN^tBuPPh₂)­FeH (Ph₂PN^tBuPPh₂ = <i>N</i>,<i>N</i>-bis­(diphenylphosphanyl)<i>tert</i>-butylamine, <b>1-H</b>) and 1-benzyl-3-carbamoylpyridinium cation (BNA⁺) in different solvents, we found that the solvents exert considerable influence on the hydride transfer processes. A coordinating solvent molecule such as MeCN is not only a ligand which stabilizes the organo-iron fragment producing [Cp*­(Ph₂PN^tBuPPh₂)­Fe­(NCMe)]⁺ ([<b>1</b>(NCMe)]⁺), but also assists the hydride transfer. In THF, reaction of <b>1-H</b> with BNA⁺ under high pressure of nitrogen (60 psi) giving the iron­(II)–nitrogen complex [Cp*­(Ph₂PN^tBuPPh₂)­Fe­(N₂)]⁺ ([<b>1</b>-N₂]⁺) and BNAH. In CH₂Cl₂, [<b>1</b>-N₂]⁺ catalyzes the conversion of <b>1-H</b> to Cp*­(Ph₂PN^tBuPPh₂)­FeCl (<b>1-Cl</b>), which hampers the expected hydride transfer reaction. In the presence of MeCN, the hydride transfer process in THF, CH₂Cl₂, or benzene was achieved affording the reduced BNAH and [<b>1</b>(NCMe)]⁺. New iron complexes in the [Cp*­(Ph₂PN^tBuPPh₂)­FeX]^<i>n</i>+ series (where <i>n</i> = 0, X = H or Cl; <i>n</i> = 1, X = MeCN, N₂, or Cl^–) were obtained and well characterized

Water-Soluble, Self-Assembled Molecular Cage and Two-Dimensional Framework through Flexibility Adjustment of the Precursors

The diversified self-assembly in water is a versatile and significant phenomenon with far-reaching implications in materials science, medicine, biotechnology, and various other fields. Through subtle tailoring of the amphipathic molecular structures, two completely different self-assembly behaviors in water were obtained. The precursors M1-X (X = I– or Cl–) with rigid and shorter bridges between the hydrophobic core and the hydrophilic edge form 2D framework structures, while the precursor M2-I molecule with flexible vinyl bridges gives 3D cube-like supramolecular cages. Notably, all of the single crystals of the assemblies were obtained. Single-crystal X-ray diffraction analysis provided unambiguous evidence of the 2D framework and cube-like structures

Decorating the Edges of a 2D Polymer with a Fluorescence Label

This work proves the existence and chemical addressability of defined edge groups of a 2D polymer. Pseudohexagonally prismatic single crystals consisting of layered stacks of a 2D polymer are used. They should expose anthracene-based edge groups at the six (100) but not at the two pseudohexagonal (001) and (001̅) faces. The crystals are reacted with the isotopically enriched dienophiles maleic anhydride and a C18-alkyl chain-modified maleimide. In both cases the corresponding Diels–Alder adducts between these reagents and the edge groups are formed as confirmed by solid state NMR spectroscopy. The same applies to a maleimide derivative carrying a BODIPY dye which was chosen for its fluorescence to be out of the range of the self-fluorescence of the 2D polymer crystals stemming from contained template molecules. If the crystals are excited at λ = 633 nm, their (100) faces and thus their rims fluoresce brightly, while the pseudohexagonal faces remain silent. This is visible when the crystals lie on a pseudohexagonal face. Lambda-mode laser scanning microscopy confirms this fluorescence to originate from the BODIPY dye. Micromechanical exfoliation of the dye-modified crystals results in thinner sheet packages which still exhibit BODIPY fluorescence right at the rim of these packages. This work establishes the chemical nature of the edge groups of a 2D polymer and is also the first implementation of an edge group modification similar to end group modifications of linear polymers

Graphdiyne-Doped P3CT‑K as an Efficient Hole-Transport Layer for MAPbI₃ Perovskite Solar Cells

Here we reported the doping of graphdiyne in P3CT-K in MAPbI₃ perovskite solar cells as hole-transport materials. The doping could improve the surface wettability of P3CT-K, and the resulting perovskite morphology was improved with homogeneous coverage and reduced grain boundaries. Simultaneously, it increased the hole-extraction mobility and reduced the recombination as well as improved the performance of devices. Therefore, a high efficiency of 19.5% was achieved based on improved short-circuit current and fill factor. In addition, hysteresis of the <i>J</i>–<i>V</i> curve was also obviously reduced. This work paves the way for the development of highly efficient perovskite solar cells

Additional file 1 of The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study

Supplementary Material

Additional file 2 of The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study

Supplementary Material

Controlled Synthesis of a Three-Segment Heterostructure for High-Performance Overall Water Splitting

Developing earth-abundant, highly active, and robust electrocatalysts capable of both oxygen and hydrogen evolution reactions is crucial for the commercial success of renewable energy technologies. Here we demonstrate a facile and universal strategy for fabricating transition metal (TM) sulfides by controlling the atomic ratio of TM precursors for water splitting in basic media. Density functional theory calculations reveal that the incorporation of Fe/Co can significantly improve the catalytic performance. The optimal material exhibits extremely small overpotentials of 208 mV for oxygen evolution and 68 mV for hydrogen evolution at 10 mA cm^–2 with robust long-term stability. The optimized material was used as bifunctional electrodes for overall water splitting, which delivers 10 mA cm^–2 at a very low cell voltage of 1.44 V with robust stability over 80 h at 100 mA cm^–2 without degradation, much better than the combination of Pt and RuO₂ as benchmark catalysts. The excellent water-splitting performance sheds light on the promising potential of such sulfides as high activity and robust stable electrodes

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