Leaping and Landing in Brave Spaces

Vapor-fed electrolysis of water has been performed using membrane-electrode assemblies (MEAs) incorporating earth-abundant catalysts and bipolar membranes (BPMs). Catalyst films containing CoP nanoparticles, carbon black, and Nafion were synthesized, characterized, and integrated into cathodes of MEAs. The CoP-containing MEAs exhibited stable (>16 h) vapor-fed electrolysis of water at room temperature at a current density of 10 mA cm⁻² with 350 mV of additional overvoltage relative to MEA's formed from Pt/C cathodic electrocatalysts due to slower hydrogen-evolution reaction kinetics under vapor-fed conditions and fewer available triple-phase boundaries in the catalyst film. Additionally, catalyst films containing a [NiFe]-layered double hydroxide ([NiFe]-LDH) as well as a hydroxide ion conductor, hexamethyl-p-terphenyl poly(benzimidazolium) (HMT-PMBI), were synthesized, characterized, and integrated into the anodes of the MEAs. The [NiFe]-LDH-containing MEAs exhibited overvoltages at 10 mA cm⁻² that were similar to those of IrO_x-containing MEAs for vapor-fed electrolysis of water at room temperature. A BPM was formed by pairing Nafion with HMT-PMBI, resulting in a locally alkaline environment of HMT-PMBI to stabilize the [NiFe]-LDH and a locally acidic environment to stabilize the CoP. BPM-based MEAs were stable (>16 h) for vapor-fed electrolysis of water at room temperature at a current density of 10 mA cm⁻², with a change in the pH gradient of 1 unit over 16 h of electrolysis for IrOx-containing MEAs. The stability of [NiFe]-LDH-based MEAs under vapor-fed conditions was dependent on the catalyst film morphology and resulting BPM interface, with stable operation at 10 mA cm⁻² achieved for 16 h. All MEAs exhibited a drift in the operating voltage over time associated with dehydration. These results demonstrate that earth-abundant catalysts and BPMs can be incorporated into stable, room-temperature, vapor-fed water-splitting cells operated at 10 mA cm⁻²

Electrochemical Reduction of Carbon Dioxide to Methanol in the Presence of Benzannulated Dihydropyridine Additives

Dihydropyridines (DHPs) have been postulated as active intermediates in the pyridine-mediated electrochemical conversion of CO₂ to methanol; however, the ability of isolated DHPs to facilitate methanol production in a fashion similar to that of their parent aromatic <i>N</i>-heterocycles (ANHs) has not been tested. Here, we use bulk electrolysis to show that 1,2- and 1,4-DHPs (1,2-dihydro­phenanthridine and 9,10-dihydro­acridine) can mediate the substoichiometric electrochemical reduction of CO₂ to methanol and formate with Faradaic efficiencies similar to those of the corresponding ANHs at Pt electrodes. 1,2-Dihydro­phenanthridine furthermore exhibits improved CO₂ reduction activity compared to its parent ANH (phenanthridine) at glassy carbon electrodes. These results provide the first experimental evidence for the participation of DHPs as additives in electrochemical CO₂ reduction

Phenanthridine-Containing Pincer-like Amido Complexes of Nickel, Palladium, and Platinum

Proligands based on bis­(8-quinolinyl)­amine (<b>L1</b>) were prepared containing one (<b>L2</b>) and two (<b>L3</b>) benzo-fused N-heterocyclic phenanthridinyl (3,4-benzoquinolinyl) units. Taken as a series, <b>L1</b>–<b>L3</b> provides a ligand template for exploring systematic π-extension in the context of tridentate pincer-like amido complexes of group 10 metals (<b>1-M</b>, <b>2-M</b>, and <b>3-M</b>; <b>M</b> = Ni, Pd, Pt). Inclusion of phenanthridinyl units was enabled by development of a cross-coupling/condensation route to 6-unsubstituted, 4-substituted phenanthridines (<b>4-Br</b>, <b>4-NO</b>_<b>2</b>, <b>4-NH</b>_<b>2</b>) suitable for elaboration into the target ligand frameworks. Complexes <b>1-M</b>, <b>2-M</b>, and <b>3-M</b> are redox-active; electrochemistry and UV–vis absorption spectroscopy were used to investigate the impact of π-extension on the electronic properties of the metal complexes. Unlike what is typically observed for benzannulated ligand–metal complexes, extending the π-system in metal complexes <b>1-M</b> to <b>2-M</b> to <b>3-M</b> led to only a moderate red shift in the relative highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gap as estimated by electrochemistry and similarly subtle changes to the onset of the lowest-energy absorption observed by UV–vis spectroscopy. Time-dependent density functional theory calculations revealed that benzannulation significantly impacts the atomic contributions to the LUMO and LUMO+1 orbitals, altering the orbital contributions to the lowest-energy transition but leaving the energy of this transition essentially unchanged

Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda

Artemisinin partial resistance may facilitate selection of Plasmodium falciparum resistant to combination therapy partner drugs. We evaluated 99 P. falciparum isolates collected in 2021 from northern Uganda, where resistance-associated PfK13 C469Y and A675V mutations have emerged, and eastern Uganda, where these mutations are uncommon. With the ex vivo ring survival assay, isolates with the 469Y mutation (median survival 7.3% for mutant, 2.5% mixed, and 1.4% wild type) and/or mutations in Pfcoronin or falcipain-2a, had significantly greater survival; all isolates with survival &gt;5% had mutations in at least one of these proteins. With ex vivo growth inhibition assays, susceptibility to lumefantrine (median IC50 14.6 vs. 6.9 nM, p &lt; 0.0001) and dihydroartemisinin (2.3 vs. 1.5 nM, p = 0.003) was decreased in northern vs. eastern Uganda; 14/49 northern vs. 0/38 eastern isolates had lumefantrine IC50 &gt; 20 nM (p = 0.0002). Targeted sequencing of 819 isolates from 2015-21 identified multiple polymorphisms associated with altered drug susceptibility, notably PfK13 469Y with decreased susceptibility to lumefantrine (p = 6 × 10-8) and PfCRT mutations with chloroquine resistance (p = 1 × 10-20). Our results raise concern regarding activity of artemether-lumefantrine, the first-line antimalarial in Uganda

Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda.

BACKGROUND: Partial resistance of Plasmodium falciparum to the artemisinin component of artemisinin-based combination therapies, the most important malaria drugs, emerged in Southeast Asia and now threatens East Africa. Partial resistance, which manifests as delayed clearance after therapy, is mediated principally by mutations in the kelch protein K13 (PfK13). Limited longitudinal data are available on the emergence and spread of artemisinin resistance in Africa. METHODS: We performed annual surveillance among patients who presented with uncomplicated malaria at 10 to 16 sites across Uganda from 2016 through 2022. We sequenced the gene encoding kelch 13 ( RESULTS: By 2021-2022, the prevalence of parasites with validated or candidate resistance markers reached more than 20% in 11 of the 16 districts where surveillance was conducted. The PfK13 469Y and 675V mutations were seen in far northern Uganda in 2016-2017 and increased and spread thereafter, reaching a combined prevalence of 10 to 54% across much of northern Uganda, with spread to other regions. The 469F mutation reached a prevalence of 38 to 40% in one district in southwestern Uganda in 2021-2022. The 561H mutation, previously described in Rwanda, was first seen in southwestern Uganda in 2021, reaching a prevalence of 23% by 2022. The 441L mutation reached a prevalence of 12 to 23% in three districts in western Uganda in 2022. Genetic analysis indicated local emergence of mutant parasites independent of those in Southeast Asia. The emergence of resistance was observed predominantly in areas where effective malaria control had been discontinued or transmission was unstable. CONCLUSIONS: Data from Uganda showed the emergence of partial resistance to artemisinins in multiple geographic locations, with increasing prevalence and regional spread over time. (Funded by the National Institutes of Health.)

Benefits of Substituting Sitting with Standing and Walking in Free-Living Conditions for Cardiometabolic Risk Markers, Cognition and Mood in Overweight Adults

Background: We investigated whether substituting sitting with standing and self-perceived light walking in free-living conditions would improve cardiometabolic risk factors, mood, and cognition in overweight/obese adults.Methods: In a randomized, cross-over study, 24 (m/f: 13/11) sedentary overweight/obese participants (64 ± 7 years, BMI 29 ± 2 kg/m2) followed two activity regimens of each 4 days in free-living conditions: “Sit”: sitting 13.5 h/day, standing 1.4 h/day, self-perceived light-intensity walking 0.7 h/day; for “SitLess” these activities lasted 7.6, 4.0, and 4.3 h/day, respectively. Meals were standardized and physical activity was assessed by accelerometry (activPAL). Insulin sensitivity (expressed as Matsuda-index based on an oral glucose tolerance test), circulating lipids, blood pressure, mood (pleasantness and arousal), and cognition were assessed on the morning after the activity regimens. Quality of life and sleep were assessed on the last day of the activity regimens.Results: We observed that AUC (0–190 min) for insulin decreased by 20% after SitLess vs. Sit [10,125 (656) vs. 12,633 (818); p = 0.006]. Insulin sensitivity improved by 16% after SitLess vs. Sit [Matsuda-index, mean (SEM): 6.45 (0.25) vs. 5.58 (0.25) respectively; p = 0.007]. Fasting triglycerides, non-HDL-cholesterol, and apolipoprotein B decreased by 32, 7, and 4% respectively, whereas HDL-cholesterol increased by 7% after SitLess vs. Sit (all p &lt; 0.01). Diastolic blood pressure was lower after SitLess vs. Sit (p &lt; 0.05). Pleasantness (as one marker of mood status) after the oral glucose tolerance test was higher after SitLess vs. Sit (p &lt; 0.05). There was no significant difference between regimens for cognition, quality of life and sleep.Conclusions: Reducing sitting time in free-living conditions markedly improved insulin sensitivity, circulating lipids, and diastolic blood pressure. Substituting sitting with standing and self-perceived light walking is an effective strategy to improve cardiometabolic risk factors in overweight/obese subjects