Cell Type-Specific Intralocus Interactions Reveal Oligodendrocyte Mechanisms in MS.

Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid- and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional elongation is a dominant pathway blocking oligodendrocyte maturation. Furthermore, pause release factors are frequently dysregulated in MS brain tissue. These data implicate cell-intrinsic aberrations outside of the immune system and suggest new avenues for therapeutic development. VIDEO ABSTRACT.

Multiscale biophysical analysis of nucleolus disassembly during mitosis.

During cell division, precise and regulated distribution of cellular material between daughter cells is a critical step and is governed by complex biochemical and biophysical mechanisms. To achieve this, membraneless organelles and condensates often require complete disassembly during mitosis. The biophysical principles governing the disassembly of condensates remain poorly understood. Here, we used a physical biology approach to study how physical and material properties of the nucleolus, a prominent nuclear membraneless organelle in eukaryotic cells, change during mitosis and across different scales. We found that nucleolus disassembly proceeds continuously through two distinct phases with a slow and reversible preparatory phase followed by a rapid irreversible phase that was concurrent with the nuclear envelope breakdown. We measured microscopic properties of nucleolar material including effective diffusion rates and binding affinities as well as key macroscopic properties of surface tension and bending rigidity. By incorporating these measurements into the framework of critical phenomena, we found evidence that near mitosis surface tension displays a power-law behavior as a function of biochemically modulated interaction strength. This two-step disassembly mechanism maintains structural and functional stability of nucleolus while enabling its rapid and efficient disassembly in response to cell cycle cues.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Friends or Foes: Fundamental Principles of Th-Organic Scaffold Chemistry Using Zr-Analogs as a Guide.

The fundamental interest in actinide chemistry, particularly for the development of thorium-based materials, is experiencing a renaissance owing to the recent and rapidly growing attention to fuel cycle reactors, radiological daughters for nuclear medicine, and efficient nuclear stockpile development. Herein, we uncover fundamental principles of thorium chemistry on the example of Th-based extended structures such as metal-organic frameworks in comparison with the discrete systems and zirconium extended analogs, demonstrating remarkable over two-and-half-year chemical stability of Th-based frameworks as a function of metal node connectivity, amount of defects, and conformational linker rigidity through comprehensive spectroscopic and crystallographic analysis as well as theoretical modeling. Despite exceptional chemical stability, we report the first example of studies focusing on the reactivity of the most chemically stable Th-based frameworks in comparison with the discrete Th-based systems such as metal-organic complexes and a cage, contrasting multicycle recyclability and selectivity (>97%) of the extended structures in comparison with the molecular compounds. Overall, the presented work not only establishes the conceptual foundation for evaluating the capabilities of Th-based materials but also represents a milestone for their multifaceted future and foreshadows their potential to shape the next era of actinide chemistry.

Incorporating solvent effects in DFT: insights from cation exchange in faujasites.

Zeolites are versatile materials renowned for their extra-framework cation exchange capabilities, with applications spanning diverse fields, including nuclear waste treatment. While detailed experimental characterization offers valuable insight, density functional theory (DFT) proves particularly adept at investigating ion exchange in zeolites, owing to its atomic and electronic resolution. However, the prevalent occurrence of zeolitic ion exchange in aqueous environments poses a challenge to conventional DFT modeling, traditionally conducted in a vacuum. This study seeks to enhance zeolite modeling by systematically evaluating predictive differences across varying degrees of aqueous solvent inclusion. Specifically focusing on monovalent cation exchange in Na-X zeolites, we explore diverse modeling approaches. These range from simple dehydrated systems (representing bare reference states in vacuum) to more sophisticated models that incorporate aqueous solvent effects through explicit water molecules and/or a dielectric medium. Through comparative analysis of DFT and semi-empirical DFT approaches, along with their validation against experimental results, our findings underscore the necessity to concurrently consider explicit and implicit solvent effects for accurate prediction of zeolitic ionic exchange.

Charting achievements: a two-year retrospective of the society for environmental geochemistry and health (SEGH) and the evolving strategies.

Emerging from the shadow of the COVID-19 pandemic, it is time to ground ourselves and retrospectively assess the recent achievements of SEGH over the past years. This editorial serves as a comprehensive report on the progress made in comparison to the aspirations and goals set by the society's board in 2019 (Watts et al., Environ Geochem Health 42:343-347, 2019) (Fig. 1) and reflects on the state of the SEGH community as it reached its 50th anniversary at the close of 2021 (Watts et al. Environ Geochem Health 45:1165-1171, 2023). The focus lies on how the SEGH community navigated through the extraordinary challenges posed by the COVID-19 pandemic since early 2020, and to what extent the 2023 targets have been met.

Organic Non-Nucleophilic Electrolyte Resists Carbonation during Selective CO2 Electroreduction.

The spontaneous reaction of CO2 with water and hydroxide to form (bi)carbonates in alkaline aqueous electrolytes compromises the energy and carbon efficiency of CO2 electrolyzers. We hypothesized that electrolyte carbonation could be mitigated by operating the reaction in an aprotic solvent with low water content, while also employing an exogenous non-nucleophilic acid as the proton donor to prevent parasitic capture of CO2 by its conjugate base. However, it is unclear whether such an electrolyte design could simultaneously engender high CO2 reduction selectivity and low electrolyte carbonation. We herein report selective CO2 electroreduction with low carbonate formation on a polycrystalline Au catalyst using dimethyl sulfoxide as the solvent and acetic acid/acetate as the proton-donating medium. CO2 is reduced to CO with over 90% faradaic efficiency at potentials relative to the reversible hydrogen electrode that are comparable to those in neutral aqueous electrolytes. 1H and 13C NMR studies demonstrate that only millimolar concentrations of bicarbonates are reversibly formed, that the proton activity of the medium is largely unaffected by exposure to CO2, and that low carbonation is maintained upon addition of 1 M water. This work demonstrates that electrolyte carbonation can be attenuated and decoupled from efficient CO2 reduction in an aprotic solvent, offering new electrolyte design principles for low-temperature CO2 electroreduction systems.

Effects of a Pragmatic Home-based Exercise Program Concurrent With Neoadjuvant Therapy on Physical Function of Patients With Pancreatic Cancer: The PancFit Randomized Clinical Trial.

OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer. BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer. METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes. RESULTS: One hundred fifty-one patients were randomized. Objectively measured weekly activity (153.2±135.6 and 159.8±122.8 min in Arm A and B, respectively, P =0.62) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 129.6±161.6 min in Arm A and Arm B, respectively, P =0.49) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P <0.001). 6MWD improved in both Arm A (mean change 18.6±56.8 m, P =0.01) and Arm B (27.3±68.1 m, P =0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes. CONCLUSIONS: In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery.

Fundamental Determinants of the Accuracy of Equilibrium Constants for Affinity Complexes.

The equilibrium constant of a chemical reaction is arguably the key thermodynamic parameter in chemistry; we naturally expect that equilibrium constants are determined accurately. The majority of equilibrium constants determined today are those of binding reactions that form affinity complexes, such as protein-protein, protein-DNA, and protein-small molecule. There is growing awareness that the determination of equilibrium constants for highly stable affinity complexes may be very inaccurate. However, fundamental (i.e., method-independent) determinants of accuracy are poorly understood. Here, we present a study that explicitly shows what the accuracy of equilibrium constants of affinity complexes depends on. This study reveals the critical importance of the choice of concentration of interacting components and creates a theoretical foundation for improving the accuracy of the equilibrium constants. The predicted influence of concentrations on accuracy was confirmed experimentally. The results of this fundamental study provide instructive guidance for experimentalists independently on the method they use.

A 128-channel receive array for cortical brain imaging at 7 T.

PURPOSE: A 128-channel receive-only array for brain imaging at 7 T was simulated, designed, constructed, and tested within a high-performance head gradient designed for high-resolution functional imaging. METHODS: The coil used a tight-fitting helmet geometry populated with 128 loop elements and preamplifiers to fit into a 39 cm diameter space inside a built-in gradient. The signal-to-noise ratio (SNR) and parallel imaging performance (1/g) were measured in vivo and simulated using electromagnetic modeling. The histogram of 1/g factors was analyzed to assess the range of performance. The array's performance was compared to the industry-standard 32-channel receive array and a 64-channel research array. RESULTS: It was possible to construct the 128-channel array with body noise-dominated loops producing an average noise correlation of 5.4%. Measurements showed increased sensitivity compared with the 32-channel and 64-channel array through a combination of higher intrinsic SNR and g-factor improvements. For unaccelerated imaging, the 128-channel array showed SNR gains of 17.6% and 9.3% compared to the 32-channel and 64-channel array, respectively, at the center of the brain and 42% and 18% higher SNR in the peripheral brain regions including the cortex. For R = 5 accelerated imaging, these gains were 44.2% and 24.3% at the brain center and 86.7% and 48.7% in the cortex. The 1/g-factor histograms show both an improved mean and a tighter distribution by increasing the channel count, with both effects becoming more pronounced at higher accelerations. CONCLUSION: The experimental results confirm that increasing the channel count to 128 channels is beneficial for 7T brain imaging, both for increasing SNR in peripheral brain regions and for accelerated imaging.

Variation of Benzo[a]pyrene, NNN, and NNK Levels in 16 Commercial Smokeless Tobacco Products.

This study examined the variation of benzo[a]pyrene (B[a]P), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) levels in 16 smokeless tobacco products from several different product subcategories obtained at two different locations and at two different procurement times. B[a]P quantities range from 0.6 to 160 ng/g on a wet-weight basis, whereas NNN and NNK quantities range from 276 to 10473 ng/g and 79 to 28882 ng/g, respectively. The B[a]P, NNN, and NNK quantities vary widely among various smokeless tobacco product categories and among various brands within each product subcategory. Dry snuff products contain the highest B[a]P, NNN, and NNK quantities, whereas loose and portioned snus products contain the lowest B[a]P, NNN, and NNK levels. In general, variation of B[a]P, NNN, and NNK levels across four sets of each product brand purchased six months apart and at two different locations show statistically significant differences (p < 0.05), although with a much narrower product set-to-set variability.

Convergence of case-specific epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose.

Opioid use disorder is a highly heterogeneous disease driven by a variety of genetic and environmental risk factors which have yet to be fully elucidated. Opioid overdose, the most severe outcome of opioid use disorder, remains the leading cause of accidental death in the United States. We interrogated the effects of opioid overdose on the brain using ChIP-seq to quantify patterns of H3K27 acetylation in dorsolateral prefrontal cortical neurons isolated from 51 opioid-overdose cases and 51 accidental death controls. Among opioid cases, we observed global hypoacetylation and identified 388 putative enhancers consistently depleted for H3K27ac. Machine learning on H3K27ac patterns predicted case-control status with high accuracy. We focused on case-specific regulatory alterations, revealing 81,399 hypoacetylation events, uncovering vast inter-patient heterogeneity. We developed a strategy to decode this heterogeneity based on convergence analysis, which leveraged promoter-capture Hi-C to identify five genes over-burdened by alterations in their regulatory network or "plexus": ASTN2, KCNMA1, DUSP4, GABBR2, ENOX1. These convergent loci are enriched for opioid use disorder risk genes and heritability for generalized anxiety, number of sexual partners, and years of education. Overall, our multi-pronged approach uncovers neurobiological aspects of opioid use disorder and captures genetic and environmental factors perpetuating the opioid epidemic.

Event-Related Potentials of Single-Sided Deaf Cochlear Implant Users: Using a Semantic Oddball Paradigm in Noise.

INTRODUCTION: In individuals with single-sided deafness (SSD), who are characterised by profound hearing loss in one ear and normal hearing in the contralateral ear, binaural input is no longer present. A cochlear implant (CI) can restore functional hearing in the profoundly deaf ear, with previous literature demonstrating improvements in speech-in-noise intelligibility with the CI. However, we currently have limited understanding of the neural processes involved (e.g., how the brain integrates the electrical signal produced by the CI with the acoustic signal produced by the normal hearing ear) and how modulation of these processes with a CI contributes to improved speech-in-noise intelligibility. Using a semantic oddball paradigm presented in the presence of background noise, this study aims to investigate how the provision of CI impacts speech-in-noise perception of SSD-CI users. METHOD: Task performance (reaction time, reaction time variability, target accuracy, subjective listening effort) and high density electroencephalography from twelve SSD-CI participants were recorded, while they completed a semantic acoustic oddball task. Reaction time was defined as the time taken for a participant to press the response button after stimulus onset. All participants completed the oddball task in three different free-field conditions with the speech and noise coming from different speakers. The three tasks were: (1) CI-On in background noise, (2) CI-Off in background noise, and (3) CI-On without background noise (Control). Task performance and electroencephalography data (N2N4 and P3b) were recorded for each condition. Speech in noise and sound localisation ability were also measured. RESULTS: Reaction time was significantly different between all tasks with CI-On (M [SE] = 809 [39.9] ms) having faster RTs than CI-Off (M [SE] = 845 [39.9] ms) and Control (M [SE] = 785 [39.9] ms) being the fastest condition. The Control condition exhibited significantly shorter N2N4 and P3b area latency compared to the other two conditions. However, despite these differences noticed in RTs and area latency, we observed similar results between all three conditions for N2N4 and P3b difference area. CONCLUSION: The inconsistency between the behavioural and neural results suggests that EEG may not be a reliable measure of cognitive effort. This rationale is further supported by different explanations used in past studies to explain N2N4 and P3b effects. Future studies should look to alternative measures of auditory processing (e.g., pupillometry) to gain a deeper understanding of the underlying auditory processes that facilitate speech-in-noise intelligibility.

A Study of Event-Related Potentials During Monaural and Bilateral Hearing in Single-Sided Deaf Cochlear Implant Users.

OBJECTIVES: Single-sided deafness (SSD) is characterized by a profoundly deaf ear and normal hearing in the contralateral ear. A cochlear implant (CI) is the only method to restore functional hearing in a profoundly deaf ear. In a previous study, we identified that the cortical processing of a CI signal differs from the normal-hearing ear (NHE) when directly compared using an auditory oddball paradigm consisting of pure tones. However, exactly how the brain integrates the electrical and acoustic signal is not well investigated. This study aims to understand how the provision of the CI in combination with the NHE may improve SSD CI users' ability to discriminate and evaluate auditory stimuli. DESIGN: Electroencephalography from 10 SSD-CI participants (4 participated in the previous pure-tone study) were recorded during a semantic acoustic oddball task, where they were required to discriminate between odd and even numbers. Stimuli were presented in four hearing conditions: directly through the CI, directly to the NHE, or in free field with the CI switched on and off. We examined task-performance (response time and accuracy) and measured N1, P2, N2N4, and P3b event-related brain potentials (ERPs) linked to the detection, discrimination, and evaluation of task relevant stimuli. Sound localization and speech in noise comprehension was also examined. RESULTS: In direct presentation, task performance was superior during NHE compared with CI (shorter and less varied reaction times [~720 versus ~842 msec], higher target accuracy [~93 versus ~70%]) and early neural responses (N1 and P2) were enhanced for NHE suggesting greater signal saliency. However, the size of N2N4 and P3b target-standard effects did not differ significantly between NHE and CI. In free field, target accuracy was similarly high with the CI (FF-On) and without the CI (FF-Off) (~95%), with some evidence of CI interference during FF-On (more variable and slightly but significantly delayed reaction times [~737 versus ~709 msec]). Early neural responses and late effects were also greater during FF-On. Performance on sound localization and speech in noise comprehension (S CI N NHE configuration only) was significantly greater during FF-On. CONCLUSIONS: Both behavioral and neural responses in the semantic oddball task were sensitive to CI in both direct and free-field presentations. Direct conditions revealed that participants could perform the task with the CI alone, although performance was suboptimal and early neural responses were reduced when compared with the NHE. For free-field, the addition of the CI was associated with enhanced early and late neural responses, but this did not result in improved task performance. Enhanced neural responses show that the additional input from the CI is modulating relevant perceptual and cognitive processes, but the benefit of binaural hearing on behavior may not be realized in simple oddball tasks which can be adequately performed with the NHE. Future studies interested in binaural hearing should examine performance under noisy conditions and/or use spatial cues to allow headroom for the measurement of binaural benefit.

Frequency and reasons for unplanned transfer to the primary acute care service of inpatient rehabilitation glioblastoma multiforme patients.

PURPOSE: To determine the percentage of and factors associated with unplanned transfer to the acute care service of glioblastoma multiforme acute rehabilitation inpatients. METHODS: Retrospective review of glioblastoma multiforme acute rehabilitation inpatients admitted 4/1/2016-3/31/2020 at a National Cancer Institute Comprehensive Cancer Center. RESULTS: One hundred thirty-nine consecutive admissions of unique glioblastoma multiforme acute rehabilitation inpatients were analyzed. Fifteen patients (10.7%, 95% confidence interval 6.5-17.1%) were transferred to the acute care service for unplanned reasons. The most common reasons for transfer back were neurosurgical complication 6/15(40%), neurologic decline due to mass effect 4/15(26.7%), and pulmonary embolism 2/15(13.3%). Older age (p = 0.010), infection prior to acute inpatient rehabilitation transfer (p = 0.020), and lower activity measure of post-acute care 6-click basic mobility scores (p = 0.048) were significantly associated with transfer to the acute care service. Patients who transferred to the acute care service had significantly lower overall survival than patients who did not transfer off (log-rank test p = 0.001). CONCLUSION: Acute inpatient physiatrists should closely monitor patients for neurosurgical and neurologic complications. The variables significantly associated with transfer to the acute care service may help identify patients at increased risk for medical complications who may require closer observation.

Magnetic Resonance Imaging of the Lumbar Spine: Recommendations for Acquisition and Image Evaluation from the BACPAC Spine Imaging Working Group.

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include procedures to conduct spinal imaging assessments with guidelines for standardizing the collection, reading/grading (using structured reporting with semi-quantitative evaluation using ordinal rating scales), and storage of images. This article presents the approach to image acquisition and evaluation recommended by the BACPAC Spine Imaging Working Group. While the approach is specific to BACPAC studies, it is general enough to be applied at other centers performing magnetic resonance imaging (MRI) acquisitions in patients with LBP. The herein presented SOPs are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by codifying MRI-based methods that provide standardized, non-invasive assessments of spinal pathologies. Finally, these recommended procedures may facilitate the integration of better harmonized MRI data of the lumbar spine across studies and sites within and outside of BACPAC studies.

Training of Lived Experience Workforces: A Rapid Review of Content and Outcomes.

Recently, the lived and living experience (LLE) workforce in mental health and alcohol and other drugs (AOD) sectors has expanded. Despite widespread benefit of this inclusion, some LLE practitioners have encountered personal and professional challenges in their workforce roles. An essential avenue to address these challenges is through provision of training to ensure adequate LLE role preparation, and to support integration of LLE workforces within mental health and AOD settings. We aim to understand the primary components applied in LLE training programs (i.e., content and methods), the outcomes from program participation, and to summarize observed patterns between training components and outcomes. This rapid review utilized a systematic methodology following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize existing literature on training programs for service users or carers/family in lived experience roles, in the mental health and AOD workforce. We searched CINAHL, PsycINFO, Medline, and Web of Science databases. We identified 36 relevant studies. Findings indicate short- and long-term impacts of training participation for this emerging workforce, with the most promising outcomes being increased professional knowledge and skills and improved personal psychosocial wellbeing and trauma recovery. Other positive training outcomes included high trainee satisfaction, increased application of training skills, and employment/education opportunities following training completion. Gaps and training limitations were noted in relation to the training content/delivery, trainee reservations, and personal barriers to training participation or completion. In response to program benefits and limitations investigated, we present recommendations for improving training processes for this workforce.

[Clinical characteristics of patients referred to cardio-oncology clinic].

To explore characteristics of outpatients in a single cardio-oncology clinic, patients visiting cardio-oncology clinic of Fuwai Hospital CAMS&PUMC (Beijing, China) from January 2020 to December 2021 were analyzed retrospectively. In total, 330 patients were included, the median age (Q1, Q3) was 58(46, 66) years, and there were 192 females (58.2%). The purposes for visit included an evaluation and treatment of cardiovascular adverse reactions (n=247, 74.8%), pre-antitumor therapy assessment (n=51, 15.5%), and management of primary or metastatic cardiac tumors (n=32, 9.7%). For patients with cardiovascular adverse reactions, the most common tumor type was breast cancer (n=88, 29.5%), followed by gastrointestinal cancer (n=70, 23.5%), and hematological cancers (n=62, 20.8%). Among them, 236 cases (95.5%) had received antitumor drugs in the past; 38 cases (15.4%) had a history of chest radiotherapy; some cases were complicated with hypertension (n=69, 23.2%) and/or hyperlipidemia (n=69, 23.2%); 42 cases (14.1%) had a history of coronary heart disease; and 16 cases (5.4%) were complicated with atrial fibrillation or flutter. Among 32 patients with cardiac tumors, 11 cases (34.4%) had primary malignant tumors; 6 cases (18.8%) had benign tumors; 2 cases (6.3%) had metastatic tumors; and 13 (40.6%) had unknown pathological types. This study explores the epidemiology of cardio-oncology in China and provides clinical insights for the future development of cardio-oncology. In the future, it is still necessary to study the benefits of cardio-oncology clinics and develop standardized indicators to evaluate their benefits.

f-block MOFs: A Pathway to Heterometallic Transuranics.

A novel series of heterometallic f-block-frameworks including the first examples of transuranic heterometallic 238 U/239 Pu-metal-organic frameworks (MOFs) and a novel monometallic 239 Pu-analog are reported. In combination with theoretical calculations, we probed the kinetics and thermodynamics of heterometallic actinide(An)-MOF formation and reported the first value of a U-to-Th transmetallation rate. We concluded that formation of uranyl species could be a driving force for solid-state metathesis. Density of states near the Fermi edge, enthalpy of formation, band gap, proton affinity, and thermal/chemical stability were probed as a function of metal ratios. Furthermore, we achieved 97 % of the theoretical maximum capacity for An-integration. These studies shed light on fundamental aspects of actinide chemistry and also foreshadow avenues for the development of emerging classes of An-containing materials, including radioisotope thermoelectric generators or metalloradiopharmaceuticals.

Aprotic Solvent Exposes an Altered Mechanism for Copper-Catalyzed Ethylene Electrosynthesis.

The selectivity and efficiency of Cu-catalyzed CO2 or CO electroreduction are known to be sensitive to the electrolyte composition. However, in aqueous media, changes to pH and ionic composition do not alter the electrokinetic profile of C2 product formation, commonly invoked to proceed via a rate-limiting pH-independent C-C coupling step to form an oxyanionic *CO dimer. We hypothesize that new mechanistic pathways can be exposed in an aprotic solvent-based electrolyte, where inhibited interfacial charge stabilization can favor pathways with electroneutral intermediates resulting from proton-coupled electron-transfer (PCET) steps from an exogenous donor. We herein report CO electroreduction to higher-order products on a polycrystalline Cu catalyst with dimethyl sulfoxide as the solvent and phenol as the proton donor. CO is reduced principally to C2 products including ethylene, acetate, ethylene glycol, and ethane with negligible methane production. In stark contrast to aqueous electrolytes, we observe a low Tafel slope (27 ± 1 mV dec-1) and Nernstian dependence on proton activity for ethylene formation, suggesting a dramatically different mechanism involving quasi-equilibrated PCET steps. This work highlights the critical role of the solvent environment and proton donor in dictating the mechanistic landscape of CO electroreduction, exposing new strategies for tuning product selectivity in hydrocarbon electrosynthesis.