Study Preregistration: Testing a Digital Suicide Risk Reduction Platform for Adolescents: A Pragmatic Randomized Controlled Trial.

Suicide is the second leading cause of death among adolescents, and rates of suicidal thoughts and behaviors (STBs) are climbing.1 Promising interventions such as dialectical behavior therapy (DBT) are available to treat suicidal youth, and new approaches may facilitate greater intervention engagement, adherence, and effectiveness.2 Digital tools (eg, personal smartphones) are a particularly promising avenue and could enhance existing, evidence-based interventions by providing new opportunities for assessment and intervention between sessions.

A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

Nonthermal Plasma-Stimulated C-N Coupling from CH4 and N2 Depends on the Presence of Surface CHx and Plasma-Phase CN Species.

Formation of C-N containing compounds from plasma-catalytic coupling of CH4 and N2 over various transition metals (Ni, Pd, Cu, Ag, and Au) is investigated using a multimodal spectroscopic approach, combining polarization-modulation infrared reflection-absorption spectroscopy (PM-IRAS) and optical emission spectroscopy (OES). Through sequential experiments utilizing CH4 and N2 nonthermal plasmas, we minimize plasma-phase reactions and identify key intermediates for C-N coupling on metal surfaces. Results show that simultaneous CH4 and N2 exposure with plasma stimulation produces surface C-N species. However, N2-CH4 sequential exposure does not lead to C-N species formation, while CH4-N2 sequential exposure reveals the presence of CHx surface species and CN radical species as key precursors to C-N species formation. From further analysis using X-ray photoelectron spectroscopy and liquid chromatography-mass spectrometry, the influence of exposure conditions on the degree of nitrogen incorporation and the nature of C-N species formed were revealed. The work highlights the importance of surface chemistry and exposure conditions in surface C-N coupling with plasma stimulation.

A US perspective on closing the carbon cycle to defossilize difficult-to-electrify segments of our economy.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

Observation and Characterization of Vibrationally Active Surface Species Accessed with Nonthermal Nitrogen Plasmas.

Polycrystalline Ni, Pd, Cu, Ag, and Au foils exposed to nonthermal plasma (NTP)-activated N2 are found to exhibit a vibrational feature near 2200 cm-1 in polarization-modulation infrared reflection-absorption spectroscopy (PM-IRAS) observations that are not present in the same materials exposed to N2 under nonplasma conditions. The feature is similar to that reported elsewhere and is typically assigned to chemisorbed N2. We employ a combination of temperature-dependent experiments, sequential dosing, X-ray photoelectron spectroscopy, isotopic labeling, and density functional theory calculations to characterize the feature. Results are most consistent with a triatomic species, likely NCO, with the C and O likely originating from ppm-level impurities in the ultrahigh-purity (UHP) Ar and/or N2 gas cylinders. The work highlights the potential for nonthermal plasmas to access adsorbates inaccessible thermally as well as the potential contributions of ppm-level impurities to corrupt the interpretation of plasma catalytic chemistry.

Multi-Functional Polymer Membranes Enable Integrated CO2 Capture and Conversion in a Single, Continuous-Flow Membrane Reactor under Mild Conditions.

Herein, we present a membrane-based system designed to capture CO2 from dilute mixtures and convert the captured CO2 into value-added products in a single integrated process operated continuously under mild conditions. Specifically, we demonstrate that quaternized poly(4-vinylpyridine) (P4VP) membranes are selective CO2 separation membranes that are also catalytically active for cyclic carbonate synthesis from the cycloaddition of CO2 to epichlorohydrin. We further demonstrate that quaternized P4VP membranes can integrate CO2 capture, including from dilute mixtures down to 0.1 kPa of CO2, with CO2 conversion to cyclic carbonates at 57 °C and atmospheric pressure. The catalytic membrane acts as both the CO2 capture and conversion medium, providing an energy-efficient alternative to sorbent-based capture, compression, transport, and storage. The membrane is also potentially tunable for the conversion of CO2 to a variety of products, including chemicals and fuels not limited to cyclic carbonates, which would be a transformative shift in carbon capture and utilization technology.

SMN regulates GEMIN5 expression and acts as a modifier of GEMIN5-mediated neurodegeneration.

GEMIN5 is essential for core assembly of small nuclear Ribonucleoproteins (snRNPs), the building blocks of spliceosome formation. Loss-of-function mutations in GEMIN5 lead to a neurodevelopmental syndrome among patients presenting with developmental delay, motor dysfunction, and cerebellar atrophy by perturbing SMN complex protein expression and assembly. Currently, molecular determinants of GEMIN5-mediated disease have yet to be explored. Here, we identified SMN as a genetic suppressor of GEMIN5-mediated neurodegeneration in vivo. We discovered that an increase in SMN expression by either SMN gene therapy replacement or the antisense oligonucleotide (ASO), Nusinersen, significantly upregulated the endogenous levels of GEMIN5 in mammalian cells and mutant GEMIN5-derived iPSC neurons. Further, we identified a strong functional association between the expression patterns of SMN and GEMIN5 in patient Spinal Muscular Atrophy (SMA)-derived motor neurons harboring loss-of-function mutations in the SMN gene. Interestingly, SMN binds to the C-terminus of GEMIN5 and requires the Tudor domain for GEMIN5 binding and expression regulation. Finally, we show that SMN upregulation ameliorates defective snRNP biogenesis and alternative splicing defects caused by loss of GEMIN5 in iPSC neurons and in vivo. Collectively, these studies indicate that SMN acts as a regulator of GEMIN5 expression and neuropathologies.

RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition.

The RNF43_p.G659fs mutation occurs frequently in colorectal cancer, but its function remains poorly understood and there are no specific therapies directed against this alteration. In this study, we find that RNF43_p.G659fs promotes cell growth independent of Wnt signaling. We perform a drug repurposing library screen and discover that cells with RNF43_p.G659 mutations are selectively killed by inhibition of PI3K signaling. PI3K/mTOR inhibitors yield promising antitumor activity in RNF43659mut isogenic cell lines and xenograft models, as well as in patient-derived organoids harboring RNF43_p.G659fs mutations. We find that RNF43659mut binds p85 leading to increased PI3K signaling through p85 ubiquitination and degradation. Additionally, RNA-sequencing of RNF43659mut isogenic cells reveals decreased interferon response gene expression, that is reversed by PI3K/mTOR inhibition, suggesting that RNF43659mut may alter tumor immunity. Our findings suggest a therapeutic application for PI3K/mTOR inhibitors in treating RNF43_p.G659fs mutant cancers.

Initial evaluation of the Optimal Health Program for people with diabetes: 12-month outcomes of a randomised controlled trial.

OBJECTIVE: This study aimed to evaluate if a new Mental health IN DiabeteS Optimal Health Program (MINDS OHP) compared with usual care in adults with Type 1 and Type 2 diabetes would improve psychosocial outcomes including self-efficacy and quality of life.Design and Main Outcome Measures This initial randomised controlled trial evaluated MINDS OHP compared with usual care. Participants were recruited through outpatient clinics and community organisations. The intervention group received nine sessions with assessments over twelve months. Primary outcomes were self-efficacy and quality of life. Secondary outcomes included diabetes distress and anxiety. RESULTS: There were 51 participants in the control group (mean age = 52) and 55 in the intervention group (mean age = 55). There were significant main effects of time in general self-efficacy, diabetes distress, diabetes self-efficacy, and illness perceptions, however no significant between-group differences in primary or secondary outcomes. Post-hoc analyses revealed MINDS OHP improved diabetes self-efficacy for participants with mild to severe depression and anxiety, with a small effect. CONCLUSION: Initial evaluation found MINDS OHP was associated with improved diabetes self-efficacy for adults with diabetes, for people with mild to severe levels of distress, with small effect. Further research is required to explore whether this disease-specific, collaborative care-focused intervention benefits the mental health of people with diabetes.

Operando Surface-Enhanced Raman-Scattering (SERS) for Probing CO2 Facilitated Transport Mechanisms of Amine-Functionalized Polymeric Membranes.

This work describes a new operando surface enhanced Raman spectroscopy (SERS) platform that we developed for use with polymeric membranes that includes (1) a method for preparing SERS-active polymer membranes and (2) a permeation cell with optical access for SERS characterization of membranes under realistic operating conditions. This technique enables the direct correlation of membrane structure to its performance under realistic operating conditions by combining in situ SERS characterization of the molecular structure of polymer membranes and simultaneous measurement of solute permeation rates on the same sample. Using the new operando SERS technique, this work aims to clarify the unknown mechanisms by which reactive amines facilitate CO2 transport across polyvinylamine (PVAm), a prototypical facilitated transport membrane for CO2 separations. We show that a small amount of plasmonic silver particles added to the PVAm solution prior to knife-casting selectively enhances the sensitivity to detection of chemical intermediates (e.g., carbamate) formed in the PVAm film due to the surface-enhanced Raman scattering effect with only minimal effect on the CO2 permeance and selectivity of the membrane. Operando SERS characterization of PVAm during exposure to humidified CO2/CH4 biogas mixtures at room temperature shows that CO2 permeates across PVAm primarily as carbamate species. This work clarifies the previously unknown mechanism of CO2 facilitated transport across PVAm and establishes a new operando SERS platform that can be used with a wide range of polymer membrane systems. This technique can be used to elucidate fundamental transport mechanisms in polymer membranes, to establish reliable structure-performance relationships, and for real-time diagnostics of membrane fouling, among other applications.

Direct Observation of Plasma-Stimulated Activation of Surface Species Using Multimodal In Situ/Operando Spectroscopy Combining Polarization-Modulation Infrared Reflection-Absorption Spectroscopy, Optical Emission Spectroscopy, and Mass Spectrometry.

Nonthermal plasmas (NTPs) produce reactive chemical environments, including electrons, ions, radicals, and vibrationally excited molecules, that can drive chemistry at temperatures at which such species are thermally inaccessible. There has been growing interest in the integration of conventional catalysis with reactive NTPs to promote novel chemical transformations. Unveiling the full potential of plasma-catalytic processes requires a comprehensive understanding of plasma-catalytic synergies, including characterization of plasma-catalytic surface interactions. In this work, we report on a newly designed multimodal spectroscopic instrument combining polarization-modulation infrared reflection-absorption spectroscopy (PM-IRAS), mass spectrometry, and optical emission spectroscopy (OES) for the investigation of plasma-surface interactions such as those found in plasma catalysis. In particular, this tool has been utilized to correlate plasma-phase chemistry with both surface chemistry and gas-phase products in situ (1) during the deposition of carbonaceous surface species via NTP-promoted nonoxidative coupling of methane and (2) during subsequent activation of surface deposits with an atmospheric pressure and temperature argon plasma jet on both nickel (Ni) and silicon dioxide (SiO2) surfaces. For the first time, the activation of carbonaceous surface species by a NTP on Ni and SiO2 surfaces to form hydrogen gas and C2 hydrocarbons was directly observed, where both PM-IRAS and OES measurements suggest that they may form through different pathways. This unique tool for studying plasma-surface interactions could enable more rational design of plasma-stimulated catalytic processes.

Highly Active CuOx/SiO2 Dot Core/Rod Shell Catalysts with Enhanced Stability for the Reverse Water Gas Shift Reaction.

Cu-based catalysts are highly active and selective for several CO2 conversion reactions; however, traditional monometallic Cu-based catalysts suffer poor thermal stability due to the aggregation of copper particles at high temperatures. In this work, we demonstrate a crystal engineering strategy to controllably prepare copper/silica (CuOx/SiO2) catalysts for the reverse water gas shift reaction (RWGS) at high temperatures. We show that CuOx/SiO2 catalysts derived from the in situ reduction of pure copper silicate nanotubes in a CO2 and H2 atmosphere exhibit superior catalytic activity with enhanced stability compared to traditional monometallic Cu-based catalysts for the RWGS at high temperatures. Detailed structural characterization reveals that there is a strong interaction between Cu and SiO2 in CuOx/SiO2 catalysts, which produces more Cu+ sites and smaller CuOx nanoparticles. Moreover, CuOx/SiO2 catalysts possess a unique dot core/rod shell structure, which could prevent the aggregation of Cu particles. This structural confinement effect, enhanced CO2 adsorption by Cu+, and small CuOx nanoparticles presumably caused the catalyst's extraordinary activity with enhanced stability at high temperatures.

Glucose patterns following alcohol and illicit drug use in young adults with type 1 diabetes: A flash glucose monitoring study.

INTRODUCTION: To assess the effects of alcohol and illicit drug use in young adults (age 18-35) with type 1 diabetes (T1D) on flash glucose monitor sensor glucose (SG) readings. METHODS: Twenty young adults with T1D were enrolled from a tertiary referral hospital outpatient department in Melbourne, Australia for a 6-week prospective observational study using flash glucose monitoring (FGM). Glucometrics comparing substance using days (SUEDs) to those without substance use (non-SUEDS) were analysed. The primary outcomes were the difference in mean SG values, its standard deviation and minutes/24-h period out of range (SG <3.9 mmol/L or >10.0 mmol/L) between matched SUEDs vs non-SUEDs. An interaction model with the primary effect of HbA1c on SG values was also performed. RESULTS: There were no differences in the primary outcome measures between SUEDS and non-SUEDs. However, there were differences in the regression coefficients for HbA1c and glucometrics between non-SUEDs and SUEDs for mean SG, time out of range and time with SG > 10 mmol/L. This difference was also identified between non-SUEDS and days of ≥40 g alcohol for mean SG. CONCLUSIONS: While there was no difference between glucometrics for SUEDs and non-SUEDs on primary outcomes, HbA1C was found to be a less reliable predictor of glucose patterns in the 24-h period following substance use than control days. Young adults with T1D need to monitor and respond to their glucose levels following substance use and engage in harm minimisation practices irrespective of baseline glucose control.

eVIP2: Expression-based variant impact phenotyping to predict the function of gene variants.

While advancements in genome sequencing have identified millions of somatic mutations in cancer, their functional impact is poorly understood. We previously developed the expression-based variant impact phenotyping (eVIP) method to use gene expression data to characterize the function of gene variants. The eVIP method uses a decision tree-based algorithm to predict the functional impact of somatic variants by comparing gene expression signatures induced by introduction of wild-type (WT) versus mutant cDNAs in cell lines. The method distinguishes between variants that are gain-of-function, loss-of-function, change-of-function, or neutral. We present eVIP2, software that allows for pathway analysis (eVIP Pathways) and usage with RNA-seq data. To demonstrate the eVIP2 software and approach, we characterized two recurrent frameshift variants in RNF43, a negative regulator of Wnt signaling, frequently mutated in colorectal, gastric, and endometrial cancer. RNF43 WT, RNF43 R117fs, RNF43 G659fs, or GFP control cDNA were overexpressed in HEK293T cells. Analysis with eVIP2 predicted that the frameshift at position 117 was a loss-of-function mutation, as expected. The second frameshift at position 659 has been previously described as a passenger mutation that maintains the RNF43 WT function as a negative regulator of Wnt. Surprisingly, eVIP2 predicted G659fs to be a change-of-function mutation. Additional eVIP Pathways analysis of RNF43 G659fs predicted 10 pathways to be significantly altered, including TNF-α via NFκB signaling, KRAS signaling, and hypoxia, highlighting the benefit of a more comprehensive approach when determining the impact of gene variant function. To validate these predictions, we performed reporter assays and found that each pathway activated by expression of RNF43 G659fs, but not expression of RNF43 WT, was identified as impacted by eVIP2, supporting that RNF43 G659fs is a change-of-function mutation and its effect on the identified pathways. Pathway activation was further validated by Western blot analysis. Lastly, we show primary colon adenocarcinoma patient samples with R117fs and G659fs variants have transcriptional profiles similar to BRAF missense mutations with activated RAS/MAPK signaling, consistent with KRAS signaling pathways being GOF in both variants. The eVIP2 method is an important step towards overcoming the current challenge of variant interpretation in the implementation of precision medicine. eVIP2 is available at https://github.com/BrooksLabUCSC/eVIP2.

Bridging the gap between diabetes care and mental health: perspectives of the Mental health IN DiabeteS Optimal Health Program (MINDS OHP).

BACKGROUND: Mental health problems are highly prevalent in people with type 1 diabetes mellitus (T1DM), which adversely impact physical health and quality of life. This study aimed to explore the experiences of people with T1DM who had completed the Mental health IN DiabeteS Optimal Health Program (MINDS OHP), a novel intervention developed to bridge the gap between physical and mental health care. METHOD: Participants with T1DM were invited to take part in a focus group or semi-structured interviews. Participants were recruited from outpatient and community settings. The focus group and interviews were audio-recorded and transcribed verbatim. Thematic content analysis was used and identified themes were cross-validated by researchers and member-checked by participants. RESULTS: Ten people with T1DM were included. Two key themes emerged: 'MINDS OHP experiences' and 'lived experiences of diabetes'. MINDS OHP experiences included five sub-themes: program benefits, follow-up and timing, suggested improvements, collaborative partners, and materials suitability. Lived experiences also included five sub-themes: bridging the gap between mental and physical health, support networks, stigma and shame, management intrusiveness, and adolescence and critical life points. CONCLUSIONS: The MINDS OHP for people with T1DM was generally well received, though study findings suggest a number of improvements could be made to the program, such as including family members, and consideration being given to its routine early inclusion in diabetes management, ideally in primary care.

Surface oxygenation of multicomponent nanoparticles toward active and stable oxidation catalysts.

The need for active and stable oxidation catalysts is driven by the demands in production of valuable chemicals, remediation of hydrocarbon pollutants and energy sustainability. Traditional approaches focus on oxygen-activating oxides as support which provides the oxygen activation at the catalyst-support peripheral interface. Here we report a new approach to oxidation catalysts for total oxidation of hydrocarbons (e.g., propane) by surface oxygenation of platinum (Pt)-alloyed multicomponent nanoparticles (e.g., platinum-nickel cobalt (Pt-NiCo)). The in-situ/operando time-resolved studies, including high-energy synchrotron X-ray diffraction and diffuse reflectance infrared Fourier transform spectroscopy, demonstrate the formation of oxygenated Pt-NiOCoO surface layer and disordered ternary alloy core. The results reveal largely-irregular oscillatory kinetics associated with the dynamic lattice expansion/shrinking, ordering/disordering, and formation of surface-oxygenated sites and intermediates. The catalytic synergy is responsible for reduction of the oxidation temperature by ~100 °C and the high stability under 800 °C hydrothermal aging in comparison with Pt, and may represent a paradigm shift in the design of self-supported catalysts.

Exploring the relationships between illness perceptions, self-efficacy, coping strategies, psychological distress and quality of life in a cohort of adults with diabetes mellitus.

Diabetes has a significant negative impact on mental health and quality of life (QoL). Underpinned by the Common Sense Model (CSM) the mediating role of coping patterns, self-efficacy, anxiety and depression symptoms on the relationship between illness perceptions and QoL in patients diagnosed with diabetes was evaluated. A total of 115 participants with diabetes (56, Type 1; 59, Type 2), 51% female and an average age of 52.69 (SD = 15.89) in Australia completed self-report measures of illness perceptions and psychological wellbeing. Baseline measures included illness perceptions, coping styles, psychological distress (anxiety and depression symptoms), self-efficacy, and quality of life. Mediating relationships were measured using structural equation modelling. A model of good fit was identified explaining 51% of the variation in QoL. Illness perceptions directly influenced QoL, maladaptive coping, self-efficacy, and anxiety symptoms. The relationship between illness perceptions and QoL was partially mediated by anxiety; illness perceptions and depression was fully mediated by maladaptive coping and self-efficacy; and self-efficacy and QoL was partially mediated by depressive symptoms. Findings provide validation of the CSM in a diabetes cohort. Psychological interventions likely to have the most benefit on psychological distress and QoL are those targeting mediating psychological processes, including maladaptive coping and self-efficacy.

Alpine Ski Racing Injuries.

CONTEXT: This article reviews the epidemiology of alpine ski racing-related injuries, risk factors, mechanisms of injury, and injury prevention strategies. EVIDENCE ACQUISITION: Pertinent literature from peer-reviewed publications from 1976 through 2018. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: The rate of injury in alpine ski racing is high. In general, knee injuries are the most common, with anterior cruciate ligament (ACL) disruptions being the most significant in terms of time loss from sport. Three specific mechanisms of ACL injury in alpine ski racers have recently been described (slip-catch, dynamic snowplow, and landing back-weighted). In contrast to other sports, female ski racers are not clearly at greater risk for ACL injury, especially at the highest level of competition. A high percentage of ski racers are able to return to their previous level of competition after ACL injury. Risk factors for injury and methods of injury prevention have been proposed; however, the rate of injury, particularly ACL injuries, has not decreased significantly. CONCLUSION: Alpine ski racing has a high injury rate. ACL injuries in particular remain problematic. Further study is needed to identify modifiable risk factors and implementation of injury prevention strategies.

Experiences of young adults with type 1 diabetes while using alcohol and recreational drugs: An interpretative phenomenological analysis (IPA) of semi-structured interviews.

AIMS: Alcohol and recreational drug use is common in young adults with type 1 diabetes (T1DM) and may account for increased morbidity and mortality. This study explores the motivations and experiences unique to this population while using alcohol and recreational drugs. METHODS: Semi-structured interviews focusing on substance use were performed with 16 young adults aged 18-35 with T1DM who drink alcohol (at least 50 g, 5 Australian standard drinks, in a single session) and/or used recreational drugs. A qualitative interpretative phenomenological analysis (IPA) of the interview data was performed by three clinicians with differing expertise (a psychologist, endocrinologist and addiction medicine specialist). RESULTS: A range of motivations, experiences and harm reduction strategies regarding substance use were described specific to young adults with T1DM with most aimed at mitigating the risk of hypoglycaemia. Clinicians remained the most trusted resources, however, substance use was rarely discussed at clinical encounters. Currently available information, especially for illicit drugs, was described as inadequate. CONCLUSIONS: This analysis identified experiences unique to young adults with T1DM when using alcohol and other drugs. Understanding these experiences and how these young adults attempt to mitigate the risks of substance use may lead to improved clinical interactions and management strategies.

Evolution of surface catalytic sites on thermochemically-tuned gold-palladium nanoalloys.

Nanoscale alloying constitutes an increasingly-important pathway for design of catalysts for a wide range of technologically important reactions. A key challenge is the ability to control the surface catalytic sites in terms of the alloying composition, thermochemical treatment and phase in correlation with the catalytic properties. Herein we show novel findings of the nanoscale evolution of surface catalytic sites on thermochemically-tuned gold-palladium nanoalloys by probing CO adsorption and oxidation using in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) technique. In addition to the bimetallic composition and the support, the surface sites are shown to depend strongly on the thermochemical treatment condition, demonstrating that the ratio of three-fold vs. bridge or atop Pd sites is greatly reduced by thermochemical treatment under hydrogen in comparison with that under oxygen. This type of surface reconstruction is further supported by synchrotron high-energy X-ray diffraction coupled to atomic pair distribution function (HE-XRD/PDF) analysis of the nanoalloy structure, revealing an enhanced degree of random alloying for the catalysts thermochemically treated under hydrogen. The nanoscale alloying and surface site evolution characteristics were found to correlate strongly with the catalytic activity of CO oxidation. These findings have significant implications for the nanoalloy-based design of catalytic synergy.