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Vascular endothelial growth factor (VEGF) signaling plays a central role in vascular development and maintenance of vascular homeostasis. In endothelial cells (ECs), VEGF activates the gene expression of angiogenic transcription factors (TFs), followed by induction of downstream angiogenic responsive genes. Recent findings support that histone modification dynamics contribute to the transcriptional control of genes that are important for EC functions. Lysine demethylase 2B (KDM2B) demethylates histone H3K4me3 and H3K36me2/3 and mediates the monoubiquitination of histone H2AK119. KDM2B functions as a transcriptional repressor in somatic cell reprogramming and tumor development. However, the role of KDM2B in VEGF signaling remains to be elucidated. Here, we show that KDM2B knockdown enhances VEGF-induced angiogenesis in cultured human ECs via increased migration and proliferation. In contrast, ectopic expression of KDM2B inhibits angiogenesis. The function of KDM2B may depend on its catalytic Jumonji C domain. Genome-wide analysis further reveals that KDM2B selectively controls the transcription of VEGF-induced angiogenic TFs that are associated with increased H3K4me3/H3K36me3 and decreased H2AK119ub. These findings suggest an essential role of KDM2B in VEGF signaling in ECs. As dysregulation of VEGF signaling in ECs is involved in various diseases, including cancer, KDM2B may be a potential therapeutic target in VEGF-mediated vasculopathic diseases.

The mutual separation of actinides (An) from lanthanides (Ln), using diethylenetriamine- N,N′,N″-pentaacetic acid (DTPA) or diethylenetriamine- N,N′,N″-triacetic acid-N,N″-bis(diethylacetamide) (DTBA) masking agents in the aqueous phase via diglycolamide (DGA) extraction is focused on the basis of Trivalent Actinide-Lanthanide Separations by Phosphorus-reagent Extraction from Aqueous Complexes (TALSPEAK) method. We also obtained the same separation performance using the commercially available DTPA using DTBA. In this work, we selected lactic acid (LA) of pH buffer from 10 organic acids and ethylenediamine (ED) for the pH adjustment based on the salt-free system. Approximately same D and SF values are obtained in the following conditions: TODGA-DTPA-LA-NaOH, TODGA-DTPA-LA-ED, and TODGA-DTBA-LA, except for different pH conditions (DTPA: pH 1.7–1.71, DTBA: pH 1.15). Experimental results using batchwise multi-stage extractions showed average yields of Ln (La to Gd) and Am to be 3.73% and 98.1% in the aqueous phase using DGA-DTPA-LA-ED, 3.1% and 97.0% using DGA-DTPA-LA-NaOH, and 1.61% and 98.7% using DGA-DTBA-LA. The suitable pH condition for the multi-stage extraction, using DTBA to extract over 95% Am with under 5% coextraction of Ln was limited to 1.14–1.16 throughout this work.

We studied the stepwise formation constants (β) of water-soluble diglycolamide (DGA) and dioxaoctanediamide (DOODA) for the mutual separation of Ln in a solvent extraction system. TODGA (N,N,Nʹ,Nʹ-tetraoctyl-diglycolamide) and DOODA(C8) (N,N,Nʹ,Nʹ-tetraoctyl-dioxaoctanediamide) exhibit opposite behaviors in extracting both light and heavy Ln through Ln-patterns. Metal complexes of two- and three-folding with water-soluble DOODA and DGA, respectively, were found, and each β value was calculated using distribution ratios. Taking β, their distribution ratio, D, and separation factor, SF, values into consideration, the suitable separation conditions (aqueous phase: 30 mM DOODA(C2) in 1 M HNO3; organic phase: 0.1 M TODGA in n-dodecane) of multistage extraction (10 × 10 extraction using aqueous and organic phases, including one sample solution) were determined. In this study, La, Pr, and Nd were mainly present in the aqueous phase, whereas Sm–Dy existed in the organic phase. Although these two groups can be easily separated into two phases, the resolution, Rs, values provide for little mutual separation between La–Nd and Sm–Dy under the present conditions.

It is essential to develop solvent extraction (SX), and electrodeposition (ED) processes for palladium to reduce the volume of acid and organic media. In this study, the extraction reaction of Pd(II) in chloride media using of N, N, N’, N’, N”, N”-hexaoctyl-nitrilotriacetamide (NTAamide(C8)) as a novel extractant has been demonstrated. Three diluents with high dielectric constants (acetophenone (AP), 1,2-dichloroethane (DCE), and 1-octanol (OC)) were used for the solvent extraction reaction. The slope analysis indicated that the anion exchange extraction reaction of Pd(II) was consistent with an approximately 2:1 stoichiometry for the NTAamide(C8)/AP and NTAamide(C8)/DCE systems, and 1:1 for NTAamide(C8)/OC. Moreover, the ED behavior of the extracted Pd(II) complex was investigated using cyclic voltammetry (CV). Palladium reduction was found to be an irreversible process based on analysis of the standard rate constant. A semi-integral analysis of the voltammogram determined the diffusion coefficients of the extracted Pd(II) complex in the AP, DCE, and OC systems to be 3.7 ± 0.1 × 10−10, 2.8 ± 0.1 × 10−10 and 1.5 ± 0.2 × 10−10 m2 s−1, respectively. Furthermore, consecutive extraction-electrodeposition processes using the NTAamide(C8)/AP system were carried out for five cycles. High extraction percentage (E > 91%) and current efficiency (ε > 83.1%) were attained in all cycles. The electrodeposits recovered from the extraction-electrodeposition process were identified as Pd metal through X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analyses.

Developing the conventional separation method by which minor actinides (MA) such as Am and Cm are separated from lanthanides is important with respect to their recovery and isolation from high-level radioactive waste (HLW). Owing to the chemical behavior of trivalent lanthanide and actinide ions with similar ionic radii, realizing this separation is still challenging. All lanthanides, Am, and Cm can be extracted using diglycolamide (DGA) extractants, and relatively high An/Ln separation efficiencies have been obtained using diethylenetriamine-N,N’,N”-triacetic acid-N,N”-bis(diethylacetamide) (DTBA). Referring to our previous study, where a good separation and a MA recovery of approximately 95% with the co-existence of 5% Nd in the aqueous phase were observed. To improve these results as well as the separation conditions, under modified conditions by adding lactic acid to stabilize pH, the recovery rates observed were as follows: 97.1% for average Ln metals with the co-existence of 1.59% Am in the organic phase and 98.4% for Am with the co-existence of 2.95% Ln in the aqueous phase.

We investigated the chemical behavior of lanthanides (Ln) by multistage extraction. Using 10 aqueous phases with Ln and 3 organic phases, we drew the breakthrough curves for light and middle Ln. Our study reveals that the limit of metal extraction depends on their D values and the metal concentration employed in experiments. From the multistage extractions of 15 stage aqueous phases and 15 stage organic phases, three curves (extraction curves, back-extraction curves, and separation curves) were obtained. Setting appropriate conditions, adequate separation of light Ln from middle ones can be achieved. As an example, under the condition of the separation curve experiment (aqueous phase: 0.5 M HNO3, organic phase: 0.1 M TDDGA (N,N,N',N'-tetradecyl-diglycolamide) in n-dodecane), the recovery of more than 99% of Sm in the organic phase with less than 1% of Nd can be obtained, even in the case of two metals adjacent to each other in the Ln series.

The alpha 7 nicotinic acetylcholine receptor (nAChR α7) is composed of five α7 subunits arranged symmetrically around a central pore. nAChR α7 is localized in the central nervous system and immune cells and could be a target for treating Alzheimer’s disease and schizophrenia. Acetylcholine (ACh) is a ligand that opens the channel, although prolonged application results in a decrease in the response. Ivermectin (IVM) was reported as one of the positive allosteric modulators, since the binding of IVM to the channel enhances ACh-evoked alpha 7 currents. The molecular dynamics of the ligand-bound state of nAChR α7 have not been exhaustively studied. We utilized a diffracted X-ray tracking method to monitor the twisting and tilting motion of nAChR α7 without a ligand, with ACh, with IVM, and with both ACh and IVM (ACh_IVM). The results showed that nAChR α7 twisted counterclockwise with the channel opening in the presence of ACh and clockwise without the channel opening in the presence of IVM. The mechanism of channel opening may be due to the twisting of the five α7 subunits together, where one or more of them are squeezed and move downward or upward.

In this study, phosphonium-based ionic liquids (IL), i.e., triethyl-n-pentyl, triethyl-n-octyl, and triethyl-n-dodecyl phosphonium bis(trifluoromethyl-sulfonyl)amide, [P222X][NTf2], (X = 5, 8, and 12) were investigated for Au(III) extraction. The IL–Au complex was identified as [P2225][AuCl4] using UV–Vis–NIR and Raman spectroscopic analyses. Slope analyses with the concentration dependence of [P222X+] confirmed the anion-exchange mechanism of Au(III) extraction by [P222X+] (X = 5, 8, and 12). The enthalpy, entropy, and Gibbs free energy for Au(III) extraction were determined using thermodynamic analysis, indicating that lower temperatures had a positive effect on the Au(III) extraction. Electrochemical analysis revealed that extracted Au(III) can be reduced in two steps: (i) Au(III) + 2e− → Au(I), (ii) Au(I) + e− → Au(0)]. The diffusion coefficients of the extracted Au(III) species in [P222X][NTf2] (X = 5, 8, and 12) were evaluated from 323 to 373 K using semi-integral and semi-differential analyses. Because of the viscosity of the IL medium, the diffusion coefficient of the extracted Au(III) increases with increasing alkyl chain length. The 4f7/2 spectrum based on X-ray photoelectron spectroscopy revealed that the Au electrodeposits obtained after 10 cycles of continuous extraction and electrodeposition were in the metallic state., Accepted Manuscript

Density functional theory calculation is applied to predict the stability constants for Eu3+ and Am3+ complexes in aqueous solution for molecular modelling of novel separation agents for minor acti...

An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vaccine antigen. Nasal distribution and retention studies using a 3D nasal cavity model and manganese-enhanced MRI were conducted by administering nasal dye and manganese powder formulations with the applied technology. Systemic and mucosal immune responses for the nasal OVA powder formulation were evaluated by determining serum IgG and nasal wash IgA antibody titers. The nasal dye and manganese powder formulations showed wider distribution and longer retention time than did a nasal liquid formulation. The nasal OVA powder formulation also showed comparable and higher antigen-specific IgG antibody titer to an injection and nasal liquid formulation, respectively. Furthermore, antigen-specific IgA antibody response was detected only for the nasal OVA powder formulation. The present study suggests that the technology, originally designed for drug absorption, is promising for nasal vaccines, enabling both a mucosal immunity response as the first line of defense and systemic immunity response as a second line of defense against infection.

We investigated the solvent extraction of four rare earth (RE) elements (Pr, Nd, Tb, and Dy) from Nd-Fe-B magnets using mixtures of 1-(2-thienyl)-4,4,4,-trifluoro-1,3-butanedione (Htta) or 4,4,4-tr...

To achieve trichotomic separation of light lanthanides (Ln), heavy Ln, and Am, batchwise multi-stage extractions using N,N,N′,N′-tetraoctyl-diglycolamide (TODGA) extractant from organic acids are studied. This technique has the advantages of both solvent extraction and chromatography, which enable successive separation and management of large volumes of aqueous solutions. Malonic acid (M-Acid) is used as the main component of the aqueous phase. It is clear that the separation factor for Nd/Am from M-Acid and that for La/Am from M-Acid + HNO3 are both around 30, thus we plan to conduct these separations.

Lanthanide (Ln) extractions from organic acids to n-dodecane by N,N,N′,N′-tetraoctyl-diglycolamide (TODGA) were conducted. Four organic acids (lactic acid, malonic acid, tartaric acid, and citric a...

The mutual separation of lanthanides has been studied by multi-stage extraction using an extractant, DGA (diglycolamide) compounds. N,N,N',N'-tetraoctyl-DGA (TODGA) has a high extractability to lanthanides and a relatively high separation factor (SF) between Dy and Nd (SF of over 20) from HNO3 media. Complete separation with such SF values can be achieved by multi-stage extraction. Less information on multi-stage extraction compared to batch extraction has been presented up to now. We thus conducted a basic study. By confirming the experimental data to be identical to calculations, the sample solution including both metals was employed for batchwise multi-stage extraction. Ninety-seven percent of Dy with under detection limit of Nd could be recovered into the organic phase from Nd with a ten-times higher concentration than Dy using the condition, 0.1 M TODGA/n-dodecane and 0.3 M HNO3 by the multi extraction of 9 × 9 stages for organic and aqueous phases.

The major problem of near-infrared spectroscopy (NIRS) for brain activity measurement during verbal fluency task is the overlapping forehead scalp blood flow (FBF) on the target cerebral blood flow (CBF). There could be among-individual differences in the influence of FBF on CBF. We investigated effects of FBF on CBF by comparing signals obtained through a laser Doppler flowmeter (LDF) and NIRS using the modified Beer-Lambert Law (MBLL). Among 25 healthy individuals, 7 participants showed a strong correlation between LDF and NIRS signals (r

A novel hydrometallurgical process involving leaching, precipitation, solvent extraction (SX) using phosphonium-based ionic liquids (ILs), and crystallization stripping was developed in this study. First, the spent catalyst was completely leached in distilled water at 343 K for 24 h. The leaching percentage of W(VI) was >99.9% according to ICP/SEM/EDX analysis. After leaching, the phosphate ions were separated by precipitation using Fe(NO3)3･9H2O as the precipitating agent. The separation percentage of phosphate was 90.8% at pH 8.11 according to ion-chromatography (IC) analysis. After the removal of phosphate, Alamine 336 and triethyl-n-pentyl phosphonium bis(trifluoromethylaulfonyl)amide ([P2225][NTf2]) were used as the extractant and diluent, respectively, for SX. The extraction percentage (E) of W(VI) reached 94.6% at pH 1.03, and the separation factor, W/P, was 101. The extraction mechanism of W(VI) was based on the ion association reaction related to the extracted complex, [(R3NH)nHxWyOz]IL, where x, y, z, and n are pH-dependent stoichiometric coefficients. After SX, the stripping percentage of W(VI) reached 100% at pH 8. Finally, crystallization proceeded at pH ≈ 4.5, and the obtained precipitate was identified to be ammonium paratungstate (NH4)10(H2W12O42)･4H2O by XRD analysis. A series of novel hydrometallurgical processes using ILs led us to conclude that W(VI) was efficiently recovered from the spent tungstophosphate catalyst.

Thin film composite (TFC) membranes are the most widely used technology in reverse osmosis (RO)-based desalination processes, due to their desirable separation performance derived from the combined structure of the porous support and thin film active layer. Typically, TFC membranes are fabricated via an interfacial polymerization (IP) technique, where the porous substrate plays an indispensable role in forming the thin film layer. In this study, a porous polyketone membrane with a fibrous structure and intrinsically moderate hydrophilicity prepared using non-solvent induced phase separation (NIPS) was employed as the substrate to explore its suitability for fabricating high-performance TFC membranes. Investigations on structure control and chemistry regulation via the NIPS process and in-situ post-treatment revealed that porous polyketone substrates display different morphologies and chemistries, significantly altering the thin layer formation during IP. The resulting TFC membranes exhibited up to 14-fold permeance difference, which was attributed to the variance of “ridge-and-valley” structures in different thin film layers formed on different polyketone substrates. It was found that a polyketone membrane with an appropriate surface roughness could generate favorable “ridge-and-valley” structures in the thin film layer to enhance the surface area, realizing high water permeance as well as high salt rejection in reverse osmotic desalination of NaCl solution.