2D Nb2SiTe4and Nb2GeTe4: promising thermoelectric figure of merit and gate-tunable thermoelectric performance.

Recently, the experimentally synthesized Nb2SiTe4was found to be a stable layered narrow-gap semiconductor, and the fabricated field-effect transistors (FETs) based on few-layers Nb2SiTe4are good candidates for ambipolar devices and mid-infrared detection (Zhaoet al2019ACS Nano1310705-10). Here, we use first-principles combined with Boltzmann transport theory and non-equilibrium Green's function method to investigate the thermoelectric transport coefficients of monolayer Nb2XTe4(X = Si, Ge) and the gate voltage effect on the thermoelectric performance of the FET based on monolayer Nb2SiTe4. It is found that both monolayers have largep-type Seebeck coefficients due to the 'pudding-mold-type' valence band structure, and they both exhibit anisotropic thermoelectric behavior with optimal thermoelectric figure of merit of 1.4 (2.2) at 300 K and 2.8 (2.5) at 500 K for Nb2SiTe4(Nb2GeTe4). The gate voltage can effectively increase the thermoelectric performance for the Nb2SiTe4-based FET. The high thermoelectric figure of merit can be maintained in a wide temperature range under a negative gate voltage. Furthermore, the FET exhibits a good gate-tunable Seebeck diode effect. The present work suggests that Nb2XTe4monolayers are promising candidates for 2D thermoelectric materials and thermoelectric devices.

Two Novel Peptide Toxins from the Spider Cyriopagopus longipes Inhibit Tetrodotoxin-Sensitive Sodium Channels.

Sodium channels play a critical role in the generation and propagation of action potentials in excitable tissues, such as nerves, cardiac muscle, and skeletal muscle, and are the primary targets of toxins found in animal venoms. Here, two novel peptide toxins (Cl6a and Cl6b) were isolated from the venom of the spider Cyriopagopus longipes and characterized. Cl6a and Cl6b were shown to be inhibitors of tetrodotoxin-sensitive (TTX-S), but not TTX-resistant, sodium channels. Among the TTX-S channels investigated, Cl6a and Cl6b showed the highest degree of inhibition against NaV1.7 (half-maximal inhibitory concentration (IC50) of 11.0 ± 2.5 nM and 18.8 ± 2.4 nM, respectively) in an irreversible manner that does not alter channel activation, inactivation, or repriming kinetics. Moreover, analysis of NaV1.7/NaV1.8 chimeric channels revealed that Cl6b is a site 4 neurotoxin. Site-directed mutagenesis analysis indicated that D816, V817, and E818 observably affected the efficacy of the Cl6b-NaV1.7 interaction, suggesting that these residues might directly affect the interaction of NaV1.7 with Cl6b. Taken together, these two novel peptide toxins act as potent and sustained NaV1.7 blockers and may have potential in the pharmacological study of sodium channels.

Nb2SiTe4: A Stable Narrow-Gap Two-Dimensional Material with Ambipolar Transport and Mid-Infrared Response.

Two-dimensional (2D) materials with narrow band gaps (∼0.3 eV) are of great importance for realizing ambipolar transistors and mid-infrared (MIR) detections. However, most of the 2D materials studied to date have band gaps that are too large. A few of the materials with suitable band gaps are not stable under ambient conditions. In this study, the layered Nb2SiTe4 is shown to be a stable 2D material with a band gap of 0.39 eV. Field-effect transistors based on few-layer Nb2SiTe4 show ambipolar transport with a similar magnitude of electron and hole current and a high charge-carrier mobility of ∼100 cm2 V-1 s-1 at room temperature. Optoelectronic measurements of the devices show clear response to an MIR wavelength of 3.1 µm with a high responsivity of ∼0.66 AW-1. These results establish Nb2SiTe4 as a good candidate for ambipolar devices and MIR detection.

A chimeric HS4 insulator-scaffold attachment region enhances transgene expression in transfected Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells are one of the most commonly used expression systems for the production of recombinant proteins but low levels of transgene expression and transgene silencing are frequently encountered. Epigenetic regulatory elements such as the chicken ß-globin locus control region hypersensitive site 4 (HS4) and scaffold/matrix attachment regions (S/MARs) have positive effects on transgene expression. In this study, a chimeric HS4-SAR was cloned upstream or downstream of an enhanced green fluorescent protein (eGFP) expression cassette in a eukaryotic vector, and the resulting vectors were transfected into CHO cells. eGFP was detected by flow cytometry. Real-time quantitative PCR (qPCR) was used to determine copy numbers of the stably transfected cells. And fluorescence in situ hybridization (FISH) was used to detect the status of vector in the host cell chromosome. The results showed that HS4-SAR positioned downstream of the expression cassette could enhance eGFP expression by 4.83-fold compared with the control vector. There may not be a relationship between transgene copy number and gene expression level. HS4-SAR did not appear to alter the integration of the transgene into the host cell chromosome or its position in the chromosome. We found a synthetic chimeric HS4-SAR positively increased transgene expression in CHO cells.

Investigation of Binding Modes and Functional Surface of Scorpion Toxins ANEP to Sodium Channels 1.7.

The depressant ß toxin anti-neuroexcitation peptide (ANEP) from the Chinese scorpion Buthus martensii Karsch has analgesic activity by interacting with receptor site 4 of the voltage-gated sodium channels (VGSCs). Here, with molecular dynamics simulations, we examined the binding modes between ANEP and the site 4 of mice sodium channel 1.7 (mNav1.7), a subtype of VGSCs related to peripheral pain. Homology modeling, molecular mechanics, and molecular dynamics in the biomembrane environment were adopted. The results suggested that ANEP bound to the resting site 4 mainly by amino acid residues in the ß2-ß3 loop and the 'NC' domains, and the activate site 4 mainly by amino acid residues in the hydrophobic domain of N-groove and residues in the 'pharmacophore'. Effects analysis of 14 mutants in the predicted functional domains of ANEP on mouse twisting models showed that the analgesic activity of mutants L15 and E24 of the 'pharmacophore', W36, T37, W38, and T39 forming the loop between the ß2- and ß3-strands and N8, V12, C60, and K64 in the NC domain increased distinctly after these residues were substituted for Ala, respectively. The binding modes and the active sites predicted were consistent with available mutagenesis data, and which is meaningful to understand the related mechanisms of ANEP for Nav1.7.

A Vector Based on the Chicken Hypersensitive Site 4 Insulator Element Replicates Episomally in Mammalian Cells.

BACKGROUND: Gene therapy in mammalian cells requires vectors exhibiting long-term stability and high expression. Episomal gene expression vectors offer a safe and attractive alternative to those that integrate into the host cell genome. MATERIALS & METHODS: In the present study, we developed a new episomal vector based on the insulator, chicken hypersensitive site 4 (cHS4). The cHS4 element was artificially synthesized, cloned into the pEGFP-C1 vector, and used to transfect Chinese hamster ovary (CHO) and human Chang liver cells. The stably transfected cell colonies were further cultured in either the presence or absence of G418 selection. Fluorescence in situ hybridization (FISH) analysis and vector rescue experiments demonstrated that the vector replicated episomally in both CHO and human Chang liver cells. Compared with episomal vectors mediated by matrix attachment region sequences, the cHS4 element-containing vector yielded increased transgene expression levels, transfection efficiency, and stability during long-term culture. The vector was present at a very low copy number in the cells and was stably maintained over more than 100 generations without selection pressure. CONCLUSION: In conclusion, apart from a few free vector forms, the cHS4-containing vector mainly replicates episomally in mammalian cells and out- performs comparable systems in terms of yielding both higher expression levels and stability levels.

Venom Peptides From Cone Snails: Pharmacological Probes for Voltage-Gated Sodium Channels.

The venoms of cone snails provide a rich source of neuroactive peptides (conotoxins). Several venom peptide families have been identified that are either agonists (ι- and δ-conotoxins) or antagonists (µ- and µO-conotoxins) of voltage-gated sodium channels (VGSCs). Members of these conotoxin classes have been integral in identifying and characterizing specific neurotoxin binding sites on the channel. Furthermore, given the specificity of some of these peptides for one sodium channel subtype over another, conotoxins have also proven useful in exploring differences between VGSC subtypes. This chapter summarizes the current knowledge of the structure and function based on the results of conotoxin interactions with VGSCs and correlates the peptides with the phylogeny of the Conus species from which they were derived.

Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.

In our previous studies on the Iranian ß-thalassemia (ß-thal) patients, we identified an association between the severity of the ß-thal phenotype and the polymorphic palindromic site at the 5' hypersensitive site 4-locus control region (5'HS4-LCR) of the ß-globin gene cluster. Furthermore, a linkage disequilibrium was observed between this region and XmnI-HBG2 in the patient population. Based on this data, it was suggested that the well-recognized phenotype-ameliorating role assigned to positive XmnI could be associated with its linked elements in the LCR. To investigate the functional significance of polymorphisms at the 5'HS4-LCR, we studied its influence on binding of transcription factors. Web-based predictions of transcription factor binding revealed a binding site for runt-related transcription factor 1 (RUNX1), when the allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it was G. Furthermore, electromobility shift assay (EMSA) presented evidence in support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a well-known regulator of hematopoiesis, these preliminary data suggest the importance of further studies to confirm this interaction and consequently investigate its functional and phenotypical relevance. These studies could help us to understand the molecular mechanism behind the phenotype modifying role of the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been observed in previous studies.