[Analysis of a Chinese pedigree affected with Hereditary coagulation factor â ª deficiency due to variant of F11 gene].

OBJECTIVE: To explore the molecular pathogenesis of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency due to variants of the F11 gene. METHODS: A male proband with Hereditary coagulation factor Ⅺ deficiency who was admitted to the First Affiliated Hospital of Wenzhou Medical University due to urinary calculi on November 30, 2020 and his family members (7 individuals from 3 generations in total) were selected as the study subjects. Clinical data of the proband were collected, and relevant coagulation indices of the proband and his family members were determined. Genomic DNA of peripheral blood samples was extracted for PCR amplification. All exons, flanking sequences, and 5' and 3' untranslated regions of the F11 gene of the proband were analyzed by direct sequencing. And the corresponding sites were subjected to sequencing in other family members. The conservation of amino acid variation sites was analyzed by bioinformatic software, and the effect of the variant on the protein function was analyzed. Variants were graded based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The proband was a 36-year-old male. His activated partial thromboplastin time (APTT) was 89.2s, which was significantly prolonged. The FⅪ activity (FⅪ:C) and FⅪ antigen (FⅪ:Ag) were 2.0% and 3.5%, respectively, which were extremely reduced. Both the proband and his sister were found to harbor compound heterozygous variants of the F11 gene, including a c.689G>T (p.Cys230Phe) missense variant in exon 7 from their father and a c.1556G>A (p.Trp519*) nonsense variant in exon 13 from their mother. Conservation analysis indicated the Cys230 site to be highly conserved. The c.1556G>A (p.Trp519*) variant was known to be pathogenic, whilst the c.689G>T variant was classified as likely pathogenic (PM2+PM5+PP1+PP3+PP4) based on the ACMG guidelines. CONCLUSION: The c.689G>T and c.1556G>A compound heterozygous variants of the F11 gene probably underlay the pathogenesis of FⅪ deficiency in this pedigree.

Charge Transfer Gap Tuning via Structural Distortion in Monolayer 1T-NbSe2.

The Mott state in 1T-TaS2 is predicted to host quantum spin liquids (QSLs). However, its insulating mechanism is controversial due to complications from interlayer coupling. Here, we study the charge transfer state in monolayer 1T-NbSe2, an electronic analogue to TaS2 exempt from interlayer coupling, using spectroscopic imaging scanning tunneling microscopy and first-principles calculations. Monolayer NbSe2 surprisingly displays two types of star of David (SD) motifs with different charge transfer gap sizes, which are interconvertible via temperature variation. In addition, bilayer 1T-NbSe2 shows a Mott collapse by interlayer coupling. Our calculation unveils that the two types of SDs possess distinct structural distortions, altering the effective Coulomb energies of the central Nb orbital. Our calculation suggests that the charge transfer gap, the same parameter for determining the QSL regime, is tunable with strain. This finding offers a general strategy for manipulating the charge transfer state in related systems, which may be tuned into the potential QSL regime.

[Analysis of genetic variant in a Chinese pedigree with hereditary factor VIII deficiency].

OBJECTIVE: To explore the genetic basis for a patient with factor VIII deficiency. METHODS: All exons of the F13A1 and F13B genes were amplified by PCR and sequenced directly. The sequencing was performed with a reverse primer if a variant was found. Conservation of variant site was analyzed by the ClustalX software. Four online bioinformatic software including Mutation Taster, PolyPhen-2, PROVEAN and SIFT were used to predict the function of the mutation site. The Swiss-PdbViewer software was applied to analyze the changes in the protein model and intermolecular force. RESULTS: The proband was found to harbor a novel c.515G>C (p.Arg171Pro) variant of the F13A1 gene. The corresponding amino acid Arg171 is conserved among homologous species. Bioinformatic analysis indicated that Arg171Pro variant may affect the protein function. Protein model analysis showed that in the wild-type, there is one hydrogen bond between Arg171 and Pro27; one hydrogen bond between Arg171 and Thr28; two hydrogen bonds between Arg171 and Glu102. When Arg171 was mutated to Pro171, the three hydrogen bonds between Arg171 and Pro27, Glu102 are all disappeared and formed a new benzene ring which might affect the stability of the protein structure. No variant was found in the F13B gene. CONCLUSION: The Arg171Pro variant may account for the decreased FVIII level. Above finding has enriched the spectrum of F13A1 gene variants.

Hexagonal Boron Nitride-Graphene Core-Shell Arrays Formed by Self-Symmetrical Etching Growth.

The synthesis and integration of core-shell materials have been extensively explored in three-dimensional nanostructures, while they are hardly ever extended into the emerging two-dimensional (2D) research field. Herein, demonstrated by graphene (G) and hexagonal boron nitride (h-BN) and via a sequential chemical vapor deposition method, we succeed for the first time in synthesizing 2D h-BN-G core-shell arrays (CSA), which possess extremely high uniformity in shapes, sizes and distributions. Each of the core-shell units is composed of G ring-shaped shell internally filled with h-BN circular core. In addition, we perform simulations to further explain the self-symmetrical etching growth mechanism of the h-BN-G CSA, demonstrating its potential to be used as an efficient synthetic method suitable for other 2D CSA systems.

Spin-orbital Yu-Shiba-Rusinov states in single Kondo molecular magnet.

Studies of single-spin objects are essential for designing emergent quantum states. We investigate a molecular magnet Tb2Pc3 interacting with a superconducting Pb(111) substrate, which hosts unprecedented Yu-Shiba-Rusinov (YSR) subgap states, dubbed spin-orbital YSR states. Upon adsorption of the molecule on Pb, the degeneracy of its lowest unoccupied molecular orbitals (LUMO) is lifted, and the lower LUMO forms a radical spin via charge transfer. This leads to Kondo screening and subgap states. Intriguingly, the YSR states display two pairs of resonances with clearly distinct behavior. The energy of the inner pair exhibits prominent inter and intra molecular variation, and it strongly depends on the tip height. The outer pair, however, shifts only slightly. As is unveiled through theoretical calculations, the two pairs of YSR states originate from the ligand spin and charge-fluctuating higher LUMO, coexisting in a single molecule, but only weakly coupled presumably due to different spatial distribution. Our work paves the way for understanding complex many-body excitations and constructing molecule-based topological superconductivity.

Realization of AlSb in the Double-Layer Honeycomb Structure: A Robust Class of Two-Dimensional Material.

Exploring two-dimensional (2D) van der Waals (vdW) systems is at the forefront of materials of physics. Here, through molecular beam epitaxy on graphene-covered SiC(0001), we report successful growth of AlSb in the double-layer honeycomb (DLHC) structure, a 2D vdW material which has no direct analogue to its 3D bulk and is predicted to be kinetically stable when freestanding. The structural morphology and electronic structure of the experimental 2D AlSb are characterized with spectroscopic imaging scanning tunneling microscopy and cross-sectional imaging scanning transmission electron microscopy, which compare well to the proposed DLHC structure. The 2D AlSb exhibits a band gap of 0.93 eV versus the predicted 1.06 eV, which is substantially smaller than the 1.6 eV of bulk. We also attempt the less-stable InSb DLHC structure; however, it grows into bulk islands instead. The successful growth of a DLHC material here demonstrates the feasibility for the realization of a large family of 2D DLHC traditional semiconductors with characteristic excitonic, topological, and electronic properties.

Dimensional Crossover and Topological Phase Transition in Dirac Semimetal Na3Bi Films.

Three-dimensional (3D) topological Dirac semimetal, when thinned down to 2D few layers, is expected to possess gapped Dirac nodes via quantum confinement effect and concomitantly display the intriguing quantum spin Hall (QSH) insulator phase. However, the 3D-to-2D crossover and the associated topological phase transition, which is valuable for understanding the topological quantum phases, remain unexplored. Here, we synthesize high-quality Na3Bi thin films with √3 × âˆš3 reconstruction on graphene and systematically characterize their thickness-dependent electronic and topological properties by scanning tunneling microscopy/spectroscopy in combination with first-principles calculations. We demonstrate that Dirac gaps emerge in Na3Bi films, providing spectroscopic evidence of dimensional crossover from a 3D semimetal to a 2D topological insulator. Importantly, the Dirac gaps are revealed to be of sizable magnitudes on three and four monolayers (72 and 65 meV, respectively) with topologically nontrivial edge states. Moreover, the Fermi energy of a Na3Bi film can be tuned via a certain growth process, thus offering a viable way for achieving charge neutrality in transport. The feasibility of controlling Dirac gap opening and charge neutrality enables realizing intrinsic high-temperature QSH effect in Na3Bi films and achieving potential applications in topological devices.