Rare Gain-of-Function KCND3 Variant Associated with Cerebellar Ataxia,Parkinsonism, Cognitive Dysfunction,and Brain Iron Accumulation

Loss-of-function mutations in the K_V4.3 channel-encoding KCND3 gene are linked to neurodegenerative cerebellar ataxia. Patients suffering from neurodegeneration associated with iron deposition may also present with cerebellar ataxia. The mechanism underlying brain iron accumulation remains unclear. Here, we aim to ascertain the potential pathogenic role of KCND3 variant in iron accumulation-related cerebellar ataxia. We presented a patient with slowly progressive cerebellar ataxia, parkinsonism, cognitive impairment, and iron accumulation in the basal ganglia and the cerebellum. Whole exome sequencing analyses identified in the patient a heterozygous KCND3 c.1256G>A (p.R419H) variant predicted to be disease-causing by multiple bioinformatic analyses. In vitro biochemical and immunofluorescence examinations revealed that, compared to the human K_V4.3 wild-type channel, the p.R419H variant exhibited normal protein abundance and subcellular localization pattern. Electrophysiological investigation, however, demonstrated that the K_V4.3 p.R419H variant was associated with a dominant increase in potassium current amplitudes, as well as notable changes in voltage-dependent gating properties leading to enhanced potassium window current. These observations indicate that, in direct contrast with the loss-of-function KCND3 mutations previously reported in cerebellar ataxia patients, we identified a rare gain-of-function KCND3 variant that may expand the clinical and molecular spectra of neurodegenerative cerebellar disorders associated with brain iron accumulation.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Genetic Dominant Variants in STUB1, Segregating in Families with SCA48, Display In Vitro Functional Impairments Indistinctive from Recessive Variants Associated with SCAR16

Variants in STUB1 cause both autosomal recessive (SCAR16) and dominant (SCA48) spinocerebellar ataxia. Reports from 18 STUB1 variants causing SCA48 show that the clinical picture includes later-onset ataxia with a cerebellar cognitive affective syndrome and varying clinical overlap with SCAR16. However, little is known about the molecular properties of dominant STUB1 variants. Here, we describe three SCA48 families with novel, dominantly inherited STUB1 variants (p.Arg51_Ile53delinsProAla, p.Lys143_Trp147del, and p.Gly249Val). All the patients developed symptoms from 30 years of age or later, all had cerebellar atrophy, and 4 had cognitive/psychiatric phenotypes. Investigation of the structural and functional consequences of the recombinant C-terminus of HSC70-interacting protein (CHIP) variants was performed in vitro using ubiquitin ligase activity assay, circular dichroism assay and native polyacrylamide gel electrophoresis. These studies revealed that dominantly and recessively inherited STUB1 variants showed similar biochemical defects, including impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP. Our findings expand the molecular understanding of SCA48 but also mean that assumptions concerning unaffected carriers of recessive STUB1 variants in SCAR16 families must be re-evaluated. More investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases.     

CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical,Dysmorphic and Structural-Functional Findings

The CACNA1A gene encodes the pore-forming α_1A subunit of the voltage-gated Ca_V2.1 Ca²⁺ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two α_1A affected residues are fully conserved throughout evolution and among the whole human Ca_V channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.     

Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of KV10.1 Pore Blockers

The K_V10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit K_V10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the K_V10.1–inhibitor complex, there remains the need for new strategies to identify selective K_V10.1 inhibitors and to understand the binding modes of the known K_V10.1 inhibitors. To investigate these binding modes in the central cavity of K_V10.1, a unique approach was used that allows derivation and analysis of ligand–protein interactions from molecular dynamics trajectories through pharmacophore modeling. The final molecular dynamics-derived structure-based pharmacophore model for the simulated K_V10.1–ligand complexes describes the necessary pharmacophore features for K_V10.1 inhibition and is highly similar to the previously reported ligand-based hERG pharmacophore model used to explain the nonselectivity of K_V10.1 pore blockers. Moreover, analysis of the molecular dynamics trajectories revealed disruption of the π–π network of aromatic residues F359, Y464, and F468 of K_V10.1, which has been reported to be important for binding of various ligands for both K_V10.1 and hERG channels. These data indicate that targeting the K_V10.1 channel pore is also likely to result in undesired hERG inhibition, and other potential binding sites should be explored to develop true K_V10.1-selective inhibitors as new anticancer agents.     

Electrochemical performance of the carbon coated Li3V2(PO4)3 cathode material synthesized by a sol-gel method

A carbon coated Li₃V₂(PO₄)₃ cathode material for lithium ion batteries was synthesized by a sol-gel method using V₂O₅, H₂O₂, NH₄H₂PO₄, LiOH and citric acid as starting materials, and its physicochemical properties were investigated using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) spectroscopy, scanning electron microscopy (SEM), energy dispersive analysis of X-ray (EDAX), transmission electron microscope (TEM), and electrochemical methods. The sample prepared displays a monoclinic structure with a space group of P2₁/n, and its surface is covered with a rough and porous carbon layer. In the voltage range of 3.0-4.3 V, the Li₃V₂(PO₄)₃ electrode displays a large reversible capacity, good rate capability and excellent cyclic stability at both 25 and 55 °C. The largest reversible capacity of 130 mAh g⁻¹ was obtained at 0.1C and 55 °C, nearly equivalent to the reversible cycling of two lithium ions per Li₃V₂(PO₄)₃ formula unit (133 mAh g⁻¹). It was found that the increase in total carbon content can improve the discharge performance of the Li₃V₂(PO₄)₃ electrode. In the voltage range of 3.0-4.8 V, the extraction and reinsertion of the third lithium ion in the carbon coated Li₃V₂(PO₄)₃ host are almost reversible, exhibiting a reversible capacity of 177 mAh g⁻¹ and good cyclic performance. The reasons for the excellent electrochemical performance of the carbon coated Li₃V₂(PO₄)₃ cathode material were also discussed.     

Catalytic Wet Oxidation of H<Subscript>2</Subscript>S to Sulfur on V/MgO Catalyst

The V/MgO catalysts with different V₂O₅ loadings were prepared by impregnating MgO with aqueous vanadyl sulfate solution. All of the catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). It was observed that the H₂S removal capacity with respect to vanadia content increased up to 6 wt%, and then decreased with further increase in vanadia loading. The prepared catalysts had BET surface areas of 11.3 ~ 95.9 m²/g and surface coverages of V₂O₅ of 0.1 ~ 2.97. The surface coverage calculation of V₂O₅ suggested that a vanadia addition up to a monomolecular layer on MgO support increased the H₂S removal capacity of V/MgO, but the further increase of VO _x surface coverage rather decreased that. Raman spectroscopy showed that the small domains of Mg₃(VO₄)₂ could be present on V/MgO with less than 6 wt% vanadia loading. The crystallites of bulk Mg₃(VO₄)₂ and Mg₂(V₂O₇) became evident on V/MgO catalysts with vanadia loading above 15 wt%, which were confirmed by a XRD. The TPR experiments showed that V/MgO catalysts with the loading below 6 wt% V₂O₅ were more reducible than those above 15 wt% V₂O₅. It indicated that tetrahedrally coordinated V⁵⁺ in well-dispersed Mg₃(VO₄)₂ domains could be the active species in the H₂S wet oxidation. The XPS studies indicated that the H₂S oxidation with V/MgO could proceed from the redox mechanism (V⁵⁺ V⁴⁺) and that V³⁺ formation, deep reduction, was responsible for the deactivation of V/MgO.     

Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BKCa Channel of Chromaffin Cells

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca²⁺-activated K⁺ channel (BK_Ca) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca²⁺ imaging, and computational modeling, we evaluated the effects of S1P on the Ca²⁺-activated K⁺ currents (I_K(Ca)) in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12). In outside-out patches, the open probability of BK_Ca channel was reduced with a mean-closed time increment, but without a conductance change in response to a low-concentration S1P (1 µM). The intracellular Ca²⁺ concentration (Ca_i) was elevated in response to a high-dose (10 µM) but not low-dose of S1P. The single-channel activity of BK_Ca was also enhanced by S1P (10 µM) in the cell-attached recording of chromaffin cells. In the whole-cell voltage-clamp, a low-dose S1P (1 µM) suppressed I_K(Ca), whereas a high-dose S1P (10 µM) produced a biphasic response in the amplitude of I_K(Ca), i.e., an initial decrease followed by a sustained increase. The S1P-induced I_K(Ca) enhancement was abolished by BAPTA. Current-clamp studies showed that S1P (1 µM) increased the action potential (AP) firing. Simulation data revealed that the decreased BK_Ca conductance leads to increased AP firings in a modeling chromaffin cell. Over a similar dosage range, S1P (1 µM) inhibited I_K(Ca) and the permissive role of S1P on the BK_Ca activity was also effectively observed in the PC12 cell system. The S1P-mediated I_K(Ca) stimulation may result from the elevated Ca_i, whereas the inhibition of BK_Ca activity by S1P appears to be direct. By the differentiated tailoring BK_Ca channel function, S1P can modulate stimulus-secretion coupling in chromaffin cells.     

Elasticity,mechanical and thermal properties of submicron h-AlN: in-situ high pressure ultrasonic study

Compressional (V_P) and shear (V_S) wave velocities of high pressure (P) and temperature (T) sintered submicron hexagonal aluminum nitride (h-AlN) have been measured up to 15 GPa using ultrasonic interferometry. Using finite strain equation-of-state approaches, yielding K_S0 = 293.1 ± 2.9 GPa, G₀ = 141.9 ± 1.4 GPa and K′_S = 3.72 ± 0.04, G′ = 0.52 ± 0.02. It is found that the Vickers hardness of submicron h-AlN is as high as 11.7 GPa, and its fracture toughness is up to ～4.25 MPa m^1/2. Meanwhile, based on the elastic wave velocities and density data, the elastic-related properties of h-AlN are derived as Debye temperature Θ₀ = 1006 K, Grüneisen parameter γ = 1.72 and acoustic thermal conductivity λ_acoustic = 196 W/mK. These results may provide a comprehensive elasticity and elastic-related properties of submicron h-AlN under high pressure, which may be of great importance for its uses at extreme conditions.     

Homogeneous precipitation synthesis and thermoelectric properties of Ca2Co2O5 ceramics

Abstract

Homogeneous precipitation method was applied to synthesise Ca₂Co₂O₅ powders using calcium nitrate, cobalt nitrate and urea as raw materials. Uniform plate-like Ca₂Co₂O₅ powders with an average grain size of 1 μm can be obtained by calcining the precursor for 8 h at 1073 K in the air. The Ca₂Co₂O₅ ceramics were gained after sintering for 4 h at 1083 K using uniaxial pressure moulding and then sintering technique. The thermoelectric properties of ceramic samples were measured from 303 to 973 K, and the result shows that the electrical conductivity, Seebeck coefficient, thermal conductivity and figure of merit of the sample are 2236·85 S m^?1, 175·95 μV K^?1, 1·01 W m^?1 K^?1 and 0·69 at 973 K respectively.     

Synthesis and electrochemical properties of Co-doped Li3V2(PO4)3 cathode materials for lithium-ion batteries

Co-doped Li₃V_2−xCo_x(PO₄)₃/C (x = 0.00, 0.03, 0.05, 0.10, 0.13 or 0.15) compounds were prepared via a solid-state reaction. The Rietveld refinement results indicated that single-phase Li₃V_2−xCo_x(PO₄)₃/C (0 ≤ x ≤ 0.15) with a monoclinic structure was obtained. The X-ray photoelectron spectroscopy (XPS) analysis revealed that the cobalt is present in the +2 oxidation state in Li₃V_2−xCo_x(PO₄)₃. XPS studies also revealed that V⁴⁺ and V³⁺ ions were present in the Co²⁺-doped system. The initial specific capacity decreased as the Co-doping content increased, increasing monotonically with Co content for x > 0.10. Differential capacity curves of Li₃V_2−xCo_x(PO₄)₃/C compounds showed that the voltage peaks associated with the extraction of three Li⁺ ions shifted to higher voltages with an increase in Co content, and when the Co²⁺-doping content reached 0.15, the peak positions returned to those of the unsubstituted Li₃V₂(PO₄)₃ phase. For the Li₃V_1.85Co_0.15(PO₄)₃/C compound, the initial capacity was 163.3 mAh/g (109.4% of the initial capacity of the undoped Li₃V₂(PO₄)₃) and 73.4% capacity retention was observed after 50 cycles at a 0.1 C charge/discharge rate. The doping of Co²⁺into V sites should be favorable for the structural stability of Li₃V_2−xCo_x(PO₄)₃/C compounds and so moderate the volume changes (expansion/contraction) seen during the reversible Li⁺ extraction/insertion, thus resulting in the improvement of cell cycling ability.     

A promising sol-gel route based on citric acid to synthesize Li3V2(PO4)3/carbon composite material for lithium ion batteries

Li₃V₂(PO₄)₃/carbon composite material was synthesized by a promising sol-gel route based on citric acid using V₂O₅ powder as a vanadium source. Citric acid acts not only as a chelating reagent but also as a carbon source, which enhance the conductivity of the composite material and hinder the growth of Li₃V₂(PO₄)₃ particles. The structure and morphology of the sample were characterized by TG, XRD and TEM measurements. XRD results reveal that Li₃V₂(PO₄)₃/carbon was successfully synthesized and has a monoclinic structure with space group P2₁/n. TEM images show Li₃V₂(PO₄)₃ particles are about 45 nm in diameter embeded in carbon networks. Galvanostatic charge/discharge and cyclic voltammetry measurements were used to study its electrochemical behaviors which indicate the reversibility of the lithium extraction/insertion processes. Li₃V₂(PO₄)₃/carbon performed in a voltage window (3.0-4.8 V) exhibits higher discharge capacity, better cycling stability and its discharge capacity maintains about 167.6 mAh/g at a current density of 28 mA/g after 50 cycles.     

Lithium insertion/deinsertion properties of new layered vanadium oxides obtained by oxidation of the precursor H2V3O8

The electrochemical behavior of the three new vanadium oxides M_yH_1−yV₃^VO₈ (M=Li, Na, K; y=0.6-0.9) towards lithium insertion was studied. For each compound, the main insertion phenomena, and the lithium amount which can be inserted, were determined from galvanostatic studies performed at different rates. In order to better explain the differences between the compounds, the galvanostatic intermittent titration technique was used and chronoamperometry experiments were performed. Cyclability studies have shown that the performances of M_0.6H_0.4V₃O₈ (M=Li, K) are not better than those of H₂V₃O₈. On the contrary, Na_0.9H_0.1V₃O₈ presents very interesting lithium insertion properties, with a specific capacity of 215 mAh g⁻¹ in the 1.5-4 V voltage range at C/10, and a capacity loss at the 40th cycle remaining smaller than 2.5%. Na_0.9H_0.1V₃O₈ is therefore a good candidate as positive electrode material for rechargeable lithium batteries.     

Effect of Cr dopant on the cathodic behavior of LiCoO2

Compounds of the formula LiCo_1−yCr_yO₂ (0.0≤y≤0.20 and y=1.0) have been synthesized by high temperature solid-state reaction and were characterized by XRD and FT-IR. Hexagonal a and c lattice parameters increase with increasing y as expected from ionic size effects. Cyclic voltammograms reveal that the phase transformation occurring at x=0.5 in Li_1−x(Co_1−yCr_y)O₂ is suppressed for y=0.05 and 0.10. Low-current (0.01 C; 1 C=140 mA g⁻¹) galvanostatic charging curves show that the deintercalation voltage for y=0.05 and 0.10 decrease for a given x as compared to LiCoO₂. Galvanostatic charge-discharge cycling of the Li(Co_1−yCr_y)O₂ cathodes at 0.14 C and 2.7-4.3 V (vs. Li) show that increasing amount of chromium content in the LiCoO₂ lattice drastically reduces the amount of Li that can be reversibly cycled. Ex-situ XRD of the cycled cathodes show that slight cation-mixing occurs in the layered structure for y=0.05 and 0.10 and could be the reason for their poor electrochemical performance. Reversible Li intercalation/deintercalation is not possible in LiCrO₂ in the voltage range 2.7-4.3 V.     

Long-term cyclability and high-rate capability of Li3V2(PO4)3/C cathode material using PVA as carbon source

The Li₃V₂(PO₄)₃/C composite cathode material is synthesized via a simple carbothermal reduction reaction route using polyvinyl alcohol (PVA) as both reduction agent and carbon source. The XRD pattern shows that the as-prepared Li₃V₂(PO₄)₃/C composite has a monoclinic structure with space group P2₁/n. The result of XPS shows the oxidation state of V in the Li₃V₂(PO₄)₃/C composite is +3. The Raman spectrum reveals that the coating carbon has a good structure with a low I_D/I_G ratio. The high-quality carbon can not only enhance the electronic conductivity of the Li₃V₂(PO₄)₃/C composite but also prevent the growth of the particle size. The electrochemical performance, which is especially notable for its high-rate performance, is excellent. It delivers an initial discharge capacity of 105.3 mAh/g at 5 C, which is retained as high as 90% after 2000 cycles. No capacity loss can be observed up to 300 cycles under 20 C rate condition. Our experimental results suggest that this compound can be a candidate as cathode materials for the power batteries of hybrid electric vehicles (HEVs) and electric vehicles (EVs) in the future.     

Lithium insertion property of Li2 2V2O5·nH2O

Lithium vanadium oxides have been prepared by the new solution processing in an aqueous hydrogen peroxide solution with lithium and vanadium alkoxides, LiO-n-C₃H₇ and VO(O-i-C₃H₇)₃, at low temperature, compared with conventional high temperature solid state reaction. Oxides having a layered structure isomorphic to that of γ-phase Li_xV₂O₅ were obtained. This “γ-like phase” oxide can be obtained at the nominal Li/V ratio of 1.5 almost as a single phase. However, formation of ω phase cannot be confirmed. The γ-like phase oxide contained water and organic compounds, and the water content n in Li_xV₂O₅·nH₂O was found to be about 2.4 for the γ-like phase oxide. Further as the result of the atomic absorption spectrometric method, the lithium content x in Li_xV₂O₅·nH₂O was estimated to be 2.2, and water molecules presumably exist in the interlayer space.Water content of the γ-like phase oxides, affects charge and discharge behaviours markedly. The lithium extraction-insertion capacity of the γ-like phase oxides were smaller, but the oxides had higher average potential compared with those of γ-phase oxide. As water content of γ-like phase oxides decreased, the lithium extraction-insertion capacity increased. Moreover, it should be noted that the average potential of γ-like phase oxides is at least 1 V higher than that of γ-LiV₂O₅.     

Dynamic analysis of removal and selective oxidation of H2S to elemental sulfur over Cu-V and Cu-V-Mo mixed oxides in a fixed bed reactor

Selective oxidation of H₂S to elemental sulfur was studied using the Cu-V and Cu-V-Mo mixed oxide catalysts with different O₂/H₂S ratios between 0 and 3. High activities and high sulfur selectivities reaching 0.98 were obtained with the Cu-V catalyst. The Cu-V-Mo mixed oxide catalyst showed higher activity with a somewhat less selectivity. The Cu-V catalyst, which was originally in the form of α-Cu₂V₂O₇, was converted to Cu₃VS₄, CuS and VO_x during the initial stages of reaction. Oxidized form of the catalyst resulted in the formation of mostly SO₂. Partially reduced catalyst containing V⁺² and V⁺⁴ was highly selective for the production of elemental sulfur, which was produced by a series of redox reactions involving lattice oxygen.     

Structure and electrochemical behavior of lithium vanadate materials for lithium batteries

New vanadate compounds having the molecular structure Li_xMg_1−xV_2−xMo_xO₆ (0 ≤ x ≤ 1) were studied. Six samples were prepared by sol-gel process from precursor using the following ratios of x = 0, 0.2, 0.4, 0.6, 0.8 and 1, respectively. These samples were labeled S1, S2, S3, S4, S5 and S6. The final process of firing occurred at 750 °C for 18 h in air. The prepared materials were characterized by XRD, SEM, IR, electron spin resonance (ESR) and magnetic measurements. The morphologies of S1, S2, S5 and S6 are prismatic as they have monoclinic crystal structures. S3 and S4 differ in the crystal morphology from the other previous samples due to their triclinic crystal lattice structure. IR spectra revealed that the bond lengths of the vanadyl groups ν_VO, ν_{sy V-O} and σ_V-O increase in the same direction from S1 to S6. The data of the ESR explain the existence of V⁴⁺ beside V⁵⁺ in S1, S4 and S6 and also presence of Mo⁵⁺ with Mo⁶⁺ in S4 and S6. S4 exhibited better magnetic susceptibility and saturated magnetization than the other samples. The first specific discharge capacities of the samples were performed. S4 showed the maximum specific capacity of 265 mAh g⁻¹ in comparison with the other samples. Cyclic voltammogram of S4 exhibited the highest current intensity in comparison with the other samples. This sample showed two peaks at 0.53 and 1.3 V versus Li/Li⁺ characterizing double de-insertions of two lithium atoms from Li_1.6Mg_0.4V_1.4Mo_0.6O_6−x and Li_0.6Mg_0.4V_1.4Mo_0.6O₆, respectively. Also, two additional peaks were characterized for the oxidation of Mo⁵⁺ to Mo⁶⁺ and V⁴⁺ to V⁵⁺ at 3.5 and 4 V, respectively.     

The key factor determining the anodic deposition of vanadium oxides

This work demonstrates that anodic deposition of vanadium oxide (denoted as VO_x·nH₂O) can be considered as the chemical co-precipitation of V⁵⁺ and V⁴⁺ oxy-/hydroxyl species and the accumulation of V⁵⁺ species at the vicinity of electrode surface is the key factor for the successful anodic deposition of VO_x·nH₂O at a potential much more negative than the equilibrium potential of the oxygen evolution reaction (OER). The results of in situ UV-vis spectra show that the V⁴⁺/V⁵⁺ ratio near the electrode surface can be controlled by varying the applied potential, leading to different, three-dimensional (3D) nanostructures of VO_x·nH₂O. The accumulation of V⁵⁺ species due to V⁴⁺ oxidation at potentials ≥0.4 V (vs. Ag/AgCl) has been found to be very similar to the phenomenon by adding H₂O₂ in the deposition solution. The X-ray photoelectron spectroscopic (XPS) results show that all VO_x·nH₂O deposits can be considered as aggregates consisting of mixed V⁵⁺ and V⁴⁺ oxy-/hydroxyl species with the mean oxidation state significantly increasing with the applied electrode potential.     

Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, Na_V1.3 and Na_V1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels Na_V1.3 and Na_V1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of Na_V1.3 and Na_V1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.