Enhanced Oxygen Evolution Reaction Activity of Co Ions Isolated in the Interlayer Space of Buserite MnO₂

We have fabricated a thin film of layered manganese dioxide (MnO₂) that accommodates cobalt ions in its interlayer space, constructing the so-called buserite structure, via electrodeposition and the subsequent ion-exchange. The MnO₂ layers could isolate Co²⁺ ions to provide an environment beneficial for oxygen evolution reactions (OERs) in alkaline electrolyte, where fast electron transfer and high utilization efficiency were achieved. The catalyst with isolated Co²⁺ ions exhibited a mass activity as high as 63.5 A/g_Co at an overpotential (η) of 0.4 V, which was much larger than those of Co ions bound in the oxide network. Moreover, it also exhibited excellent stability for long-term OER operation. Namely, the potential needed to generate a current density of 10 mA/cm² increased only 0.073 V during 100 h operation, and no significant change was seen after 100 consecutive potential cycles between +1.0 and +2.0 V versus the reversible hydrogen electrode

Regioselective Prins Cyclization of Allenylsilanes. Stereoselective Formation of Multisubstituted Heterocyclic Compounds

The Prins cyclization of hydroxy or amino group-containing allenylsilanes with carbonyl compounds occurred at the allenic terminus in a regio- and stereoselective manner to give the di- or trisubstituted tetrahydrofurans, tetrahydropyrans, and pyrrolidines. During the reaction, the allenic axial chirality of the starting material was efficiently transferred to the newly formed carbon chiral centers of the product

Development of Novel Decarboxylation-Urea Method toward Interlayer-Anion-Controlled Layered Double Hydroxides

Layered double hydroxides (LDHs) are representative of a 2D anionic clay. Simple and homogeneous synthesis of interlayer-anion-controlled LDH is essential for studies and industrial production. In this study, we report the one-pot synthesis of an LDH that is selective for interlayer anions, which was labeled as “decarboxylation-urea method”. We obtained LDHs intercalated with NO3–, Cl–, and SO42– by removing CO2 in this method. The ionic conductivities of the prepared LDHs were investigated for their applicability to electrolytes, and it was found that Zn–Al LDH intercalated with NO3– showed the highest ionic conductivity (18 mS cm–1). Therefore, the LDH intercalated with NO3– synthesized using the decarboxylation-urea method is promising as an alkaline solid electrolyte

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

Misfolding and aggregation of transthyretin are implicated in the fatal systemic disease known as transthyretin amyloidosis. Here, we report the development of a naringenin derivative bearing two chlorine atoms that will be efficacious for preventing aggregation of transthyretin in the eye. The amyloid inhibitory activity of the naringenin derivative was as strong as that of tafamidis, which is the first therapeutic agent targeting transthyretin in the plasma. X-ray crystal structures of the compounds in complex with transthyretin demonstrated that the naringenin derivative with one chlorine bound to the thyroxine-binding site of transthyretin in the forward mode and that the derivative with two chlorines bound to it in the reverse mode. An ex vivo competitive binding assay showed that naringenin derivatives exhibited more potent binding than tafamidis in the plasma. Furthermore, an in vivo pharmacokinetic study demonstrated that the dichlorinated derivative was significantly delivered to the eye

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis

Misfolding and aggregation of transthyretin are implicated in the fatal systemic disease known as transthyretin amyloidosis. Here, we report the development of a naringenin derivative bearing two chlorine atoms that will be efficacious for preventing aggregation of transthyretin in the eye. The amyloid inhibitory activity of the naringenin derivative was as strong as that of tafamidis, which is the first therapeutic agent targeting transthyretin in the plasma. X-ray crystal structures of the compounds in complex with transthyretin demonstrated that the naringenin derivative with one chlorine bound to the thyroxine-binding site of transthyretin in the forward mode and that the derivative with two chlorines bound to it in the reverse mode. An ex vivo competitive binding assay showed that naringenin derivatives exhibited more potent binding than tafamidis in the plasma. Furthermore, an in vivo pharmacokinetic study demonstrated that the dichlorinated derivative was significantly delivered to the eye

Incidence of features observed in each type of vascular relationship.

<p>Incidence of features observed in each type of vascular relationship.</p

Phase 1b Randomized Trial and Follow-Up Study in Uganda of the Blood-Stage Malaria Vaccine Candidate BK-SE36

<div><p>Background</p><p>Up to now a malaria vaccine remains elusive. The <i>Plasmodium falciparum</i> serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda.</p><p>Methods</p><p>We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21–40 year-olds) to 1-mL BK-SE36 (<i>BKSE1.0</i>) (<i>n</i> = 36) or saline (<i>n</i> = 20) and in Stage2 (6–20 year-olds) to <i>BKSE1.0</i> (<i>n</i> = 33), 0.5-mL BK-SE36 (<i>BKSE0.5</i>) (<i>n</i> = 33), or saline (<i>n</i> = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130–365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals.</p><p>Results</p><p>Nearly all subjects who received BK-SE36 had induration (Stage1, <i>n</i> = 33, 92%; Stage2, <i>n</i> = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56–2.43], <i>p</i> = 0.004) and 6–10 year-olds (5.71-fold [95% CI, 2.38–13.72], <i>p</i> = 0.002) vaccinated with <i>BKSE1.0.</i> Immunogenicity response to <i>BKSE0.5</i> was low and not significant (1.55-fold [95% CI, 1.24–1.94], <i>p</i> = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in <i>BKSE1.0</i> and 10 cases/33 subjects in <i>BKSE0.5 vs.</i> 29 cases/66 subjects in the control group. Risk ratio for <i>BKSE1.0</i> was 0.48 (95% CI, 0.24–0.98; <i>p</i> = 0.04).</p><p>Conclusion</p><p>BK-SE36 is safe and immunogenic. The promising potential of BK-SE36, observed in the follow-up study, warrants a double-blind phase 1/2b trial in children under 5 years.</p><p>Trial Registration</p><p>Controlled-Trials.com ISRCTN71619711 <a href="http://www.controlled-trials.com/ISRCTN71619711" target="_blank">ISRCTN71619711</a></p></div