Efficient Capture and Release of the Rare-Earth Element Neodymium in Aqueous Solution by Recyclable Covalent Organic Frameworks.

Rare-earth elements (REEs) are present in a broad range of critical materials. The development of solid adsorbents for REE capture could enable the cost-effective recycling of REE-containing magnets and electronics. In this context, covalent organic frameworks (COFs) are promising candidates for REE adsorption due to their exceptionally high surface area. Despite having attractive physical properties, COFs are heavily underutilized for REE capture applications due to their limited lifecycle in aqueous acidic environments, as well as synthetic challenges associated with the incorporation of ligands suitable for REE capture. Here, we show how the Ugi multicomponent reaction can be leveraged to postsynthetically modify imine-based COFs for the introduction of a diglycolic acid (DGA) moiety, an efficient scaffold for REE capture. The adsorption capacity of the DGA-functionalized COF was found to be more than 40 times higher than that of the pristine imine COF precursor and more than four times higher than that of the next-best reported DGA-functionalized solid support. This rationally designed COF has appealing characteristics of high adsorption capacity, fast and efficient capture and release of the REE ions, and reliable recyclability, making it one of the most promising adsorbents for solid-liquid REE ion extractions reported to date.

Catalytic Hydrogenolysis by Atomically Dispersed Iron Sites Embedded in Chemically and Redox Non-innocent N-Doped Carbon.

Atomically dispersed first-row transition metals embedded in nitrogen-doped carbon materials (M-N-C) show promising performance in catalytic hydrogenation but are less well-studied for reactions with more complex mechanisms, such as hydrogenolysis. Their ability to catalyze selective C-O bond cleavage of oxygenated hydrocarbons such as aryl alcohols and ethers is enhanced with the participation of ligands directly bound to the metal ion as well as longer-range contributions from the support. In this article, we describe how Fe-N-C catalysts with well-defined local structures for the Fe sites catalyze C-O bond hydrogenolysis. The reaction is facilitated by the N-C support. According to spectroscopic analyses, the as-synthesized catalysts contain mostly pentacoordinated FeIII sites, with four in-plane nitrogen donor ligands and one axial hydroxyl ligand. In the presence of 20 bar of H2 at 170-230 °C, the hydroxyl ligand is lost when N4FeIIIOH is reduced to N4FeII, assisted by the H2 chemisorbed on the support. When an alcohol binds to the tetracoordinated FeII sites, homolytic cleavage of the O-H bond is accompanied by reoxidation to FeIII and H atom transfer to the support. The role of the N-C support in catalytic hydrogenolysis is analogous to the behavior of chemically and redox-non-innocent ligands in molecular catalysts based on first-row transition metal ions and enhances the ability of M-N-Cs to achieve the types of multistep activations of strong bonds needed to upgrade renewable and recycled feedstocks.

Reaction-Initiated Single-Molecule Tracking of Mass Transfer in Core-Shell Mesoporous Silica Particles.

Understanding the host-guest interactions in porous materials is of great importance in the field of separation science. Probing it at the single-molecule level uncovers the inter- and intraparticle inhomogeneity and establishes structure-property relationships for guiding the design of porous materials for better separation performance. In this work, we investigated the dynamics of host-guest interactions in core-shell mesoporous silica particles under in situ conditions by using a fluorogenic reaction-initiated single-molecule tracking (riSMT) approach. Taking advantage of the low fluorescence background, three-dimensional (3D) tracking of the dynamics of the molecules inside the mesoporous silica pore was achieved with high spatial precision. Compared to the commonly used two-dimensional (2D) tracking method, the 3D tracking results show that the diffusion coefficients of the molecules are three times larger on average. Using riSMT, we quantitatively analyzed the mass transfer of probe molecules in the mesoporous silica pore, including the fraction of adsorption versus diffusion, diffusion coefficients, and residence time. Large interparticle inhomogeneity was revealed and is expected to contribute to the peak broadening for separation application at the ensemble level. We further investigated the impact of electrostatic interaction on the mass transfer of molecules in the mesoporous silica pore and discovered that the primary effect is on the fraction rather than their diffusion rates of resorufin molecules undergoing diffusion.

Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection.

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.

Population Balance Equations for Reactive Separation in Polymer Upcycling.

Many polymer upcycling efforts aim to convert plastic waste into high-value liquid hydrocarbons. However, the subsequent cleavage of middle distillates to light gases can be problematic. The reactor often contains a vapor phase (light gases and middle distillates) and a liquid phase (molten polymers and waxes with a suspended or dissolved catalyst). Because the catalyst resides in the liquid phase, middle distillates that partition into the vapor phase are protected against further cleavage into light gases. In this paper, we consider a simple reactive separation strategy, in which a gas outflow removes the volatile products as they form. We combine vapor-liquid equilibrium models and population balance equations (PBEs) to describe polymer upcycling in a two-phase semibatch reactor. The results suggest that the temperature, headspace volume, and flow rate of the reactor can be used to tune selectivity toward the middle distillates, in addition to the molecular mechanism of catalysis. We anticipate that two-phase reactor models will be important in many polymer upcycling processes and that reactive separation strategies will provide ways to boost the yield of the desired products in these cases.

Detailed analysis of learning phases and outcomes in robotic and endoscopic thyroidectomy.

BACKGROUND: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy. METHODS: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency. RESULTS: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains. CONCLUSION: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery.

Two Mesoporous Domains Are Better Than One for Catalytic Deconstruction of Polyolefins.

Catalytic hydrogenolysis of polyolefins into valuable liquid, oil, or wax-like hydrocarbon chains for second-life applications is typically accompanied by the hydrogen-wasting co-formation of low value volatiles, notably methane, that increase greenhouse gas emissions. Catalytic sites confined at the bottom of mesoporous wells, under conditions in which the pore exerts the greatest influence over the mechanism, are capable of producing less gases than unconfined sites. A new architecture was designed to emphasize this pore effect, with the active platinum nanoparticles embedded between linear, hexagonal mesoporous silica and gyroidal cubic MCM-48 silica (mSiO2/Pt/MCM-48). This catalyst deconstructs polyolefins selectively into ∼C20-C40 paraffins and cleaves C-C bonds at a rate (TOF = 4.2 ± 0.3 s-1) exceeding that of materials lacking these combined features while generating negligible volatile side products including methane. The time-independent product distribution is consistent with a processive mechanism for polymer deconstruction. In contrast to time- and polymer length-dependent products obtained from non-porous catalysts, mSiO2/Pt/MCM-48 yields a C28-centered Gaussian distribution of waxy hydrocarbons from polyolefins of varying molecular weight, composition, and physical properties, including low-density polyethylene, isotactic polypropylene, ultrahigh-molecular-weight polyethylene, and mixtures of multiple, post-industrial polyolefins. Coarse-grained simulation reveals that the porous-core architecture enables the paraffins to diffuse away from the active platinum site, preventing secondary reactions that produce gases.

The Structure of Boron Monoxide.

Boron monoxide (BO), prepared by the thermal condensation of tetrahydroxydiboron, was first reported in 1955; however, its structure could not be determined. With the recent attention on boron-based two-dimensional materials, such as borophene and hexagonal boron nitride, there is renewed interest in BO. A large number of stable BO structures have been computationally identified, but none are supported by experiments. The consensus is that the material likely forms a boroxine-based two-dimensional material. Herein, we apply advanced 11B NMR experiments to determine the relative orientations of B(B)O2 centers in BO. We find that the material is composed of D2h-symmetric O2B-BO2 units that organize to form larger B4O2 rings. Further, powder diffraction experiments additionally reveal that these units organize to form two-dimensional layers with a random stacking pattern. This observation is in agreement with earlier density functional theory (DFT) studies that showed B4O2-based structures to be the most stable.

General Strategy for Incorporation of Functional Group Handles into Covalent Organic Frameworks via the Ugi Reaction.

The library of imine-linked covalent organic frameworks (COFs) has grown significantly over the last two decades, featuring a variety of morphologies, pore sizes, and applications. An array of synthetic methods has been developed to expand the scope of the COF functionalities; however, most of these methods were designed to introduce functional scaffolds tailored to a specific application. Having a general approach to diversify COFs via late-stage incorporation of functional group handles would greatly facilitate the transformation of these materials into platforms for a variety of useful applications. Herein, we report a general strategy to introduce functional group handles in COFs via the Ugi multicomponent reaction. To demonstrate the versatility of this approach, we have synthesized two COFs with hexagonal and kagome morphologies. We then introduced azide, alkyne, and vinyl functional groups, which could be readily utilized for a variety of post-synthetic modifications. This facile approach enables the functionalization of any COFs containing imine linkages.

Breaking New Ground: MBene Route toward Selective Vinyl Double Bond Hydrogenation in Nitroarenes.

Doping, or incremental substitution of one element for another, is an effective way to tailor a compound's structure as well as its physical and chemical properties. Herein, we replaced up to 30% of Ni with Co in members of the family of layered LiNiB compounds, stabilizing the high-temperature polymorph of LiNiB while the room-temperature polymorph does not form. By studying this layered boride with in situ high-temperature powder diffraction, we obtained a distorted variant of LiNi0.7Co0.3B featuring a perfect interlayer placement of [Ni0.7Co0.3B] layers on top of each other─a structural motif not seen before in other borides. Because of the Co doping, LiNi0.7Co0.3B can undergo a nearly complete topochemical Li deintercalation under ambient conditions, resulting in a metastable boride with the formula Li0.04Ni0.7Co0.3B. Heating of Li0.04Ni0.7Co0.3B in anaerobic conditions led to yet another metastable boride, Li0.01Ni0.7Co0.3B, with a CoB-type crystal structure that cannot be obtained by simple annealing of Ni, Co, and B. No significant alterations of magnetic properties were detected upon Co-doping in the temperature-independent paramagnet LiNi0.7Co0.3B or its Li-deintercalated counterparts. Finally, Li0.01Ni0.7Co0.3B stands out as an exceptional catalyst for the selective hydrogenation of the vinyl C═C bond in 3-nitrostyrene, even in the presence of other competing functional groups. This research showcases an innovative approach to heterogeneous catalyst design by meticulously synthesizing metastable compounds.

Expanded single-color barcoding in microspheres with fluorescence anisotropy for multiplexed biochemical detection.

Single-color barcoding strategies could break the limits of spectral crosstalk in conventional intensity-based fluorescence barcodes. Fluorescence anisotropy (FA), a self-referencing quantity able to differentiate spectrally similar fluorophores, is highly attractive in designing fluorescent barcodes within a limited emission window. In this study, FA-based encoding of polystyrene (PS) microspheres was realized for the first time. The FA signals of fluorophores were stabilized inside PS microspheres owing to hampered rotational motion. Fluorescent labels were incorporated with similar emission but different structures, symmetries, and lifetimes. On the one hand, Förster Resonance Energy Transfer (FRET) including homo-FRET and hetero-FRET resulted in a decrease of steady-state FA with increasing dye loading, converting conventional intensity-based codes into FA-based codes. On the other hand, mixing dyes with different intrinsic FA values generated different FA values at the same fluorescence intensity level. Single color 5-plex FA-encoded microspheres were demonstrated and decoded on a homemade microscopic FA imaging platform in real time. The FA-encoded microspheres were successfully applied to detect the oligonucleotide of the foodborne bacterium, Bacillus cereus, without spectral crosstalk between the encoding and reporting dyes. Overall, FA-based encoding with an expanded coding capacity in the FA dimension holds great potential in multiplexed high-throughput chemical and biological analyses.

Silmitasertib, a casein kinase 2 inhibitor, induces massive lipid droplet accumulation and nonapoptotic cell death in head and neck cancer cells.

BACKGROUND: Accumulating evidence shows that high expression of casein kinase 2 (CK2) and phosphorylated acetyl CoA carboxylase (pACC) in patients with squamous cell carcinoma of the head and neck (SCCHN) correlates with decreased survival rates. Computational analysis has shown that ACC is a potential substrate for CK2, and its inhibition can suppress ACC phosphorylation in vitro. CX-4945, also known as silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2 and is under clinical investigation as a treatment for malignancies. We hypothesize that inhibition of CK2 by CX-4945 can reduce CK2-downstream phosphorylation of ACC as a therapeutic strategy against SCCHN. METHODS: Three aggressive SCCHN cell lines (OSC-19, FaDu and HN31) were cultured to investigate the anticancer mechanism of the CK2 inhibitor, CX-4945. Cell cycle analysis, Annexin V/PI staining, and cleavage of PARP were performed to detect apoptosis. Western blot, electron microscopy and analysis of acidic vesicular organelle development were used to detect autophagy. Interference with cellular metabolism by CX-4945 treatment was determined by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry. RESULTS: Cellular metabolism was impeded by CX-4945 in aggressive SCCHN cells by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry, and consequently time- and dose-dependent lipid droplet accumulation and non-apoptotic cell death were observed. The lipogenic enzyme ACC was demonstrated to be associated with CK2, and its repressive phosphorylation could be removed by the CK2 inhibitor CX-4945. Overexpression of ACC resulted in impaired cell survival following transient transfection. CONCLUSION: The findings demonstrate that CK2 inhibition impairs normal cellular energy metabolism and may be an attractive therapy for treating aggressive SCCHN.

Efficacy of Blue LED Phototherapy on Sleep Quality and Behavioral and Psychological Symptoms of Dementia: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: People with dementia often experience behavioral and psychological symptoms of dementia (BPSD), which are a major cause of caregiver burden and institutionalization. Therefore, we conducted a double-blind, parallel-group randomized controlled trial to examine the efficacy of blue-enriched light therapy for BPSD in institutionalized older adults with dementia. METHODS: Participants were enrolled and randomly allocated into blue-enriched light therapy (N = 30) or the conventional light group (N = 30) for 60 min in 10 weeks with five sessions per week. The primary outcome was sleep quality measured by actigraphy and Pittsburgh Sleep Quality Index (PSQI). The secondary outcome was overall BPSD severity (Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI-NH]). The outcome indicators were assessed at baseline, mid-test, immediate posttest, 1-month, 3-month, and 6-month follow-up. The effects of the blue-enriched light therapy were examined by the generalized estimating equation model. RESULTS: Blue-enriched light therapy revealed significant differences in the objective sleep parameters (sleep efficiency: ß = 5.81, Waldχ2 = 32.60, CI: 3.82; 7.80; sleep latency: ß = -19.82, Waldχ2 = 38.38, CI:-26.09; -13.55), subjective sleep quality (PSQI: ß = -2.07, Waldχ2 = 45.94, CI: -2.66; -1.47), and overall BPSD severity (CMAI: ß = -0.90, Waldχ2 = 14.38, CI: -1.37; -0.44) (NPI-NH: ß = -1.67, Waldχ2 = 30.61, CI: -2.26; -1.08) compared to conventional phototherapy immediate posttest, 1-month, 3-month, and 6-month follow-up. Furthermore, the effects for sleep efficiency and sleep latency lasted for up to 6 months. In the subscale analysis, the differences of the behavioral symptoms changed significantly between the groups in physical/nonaggressive (CI: -1.01; -0.26) and verbal/nonaggressive (CI: -0.97; -0.29). CONCLUSIONS: Blue-enriched light therapy is a feasible low-cost intervention that could be integrated as a comprehensive therapy program for BPSD among older adults with dementia.

Global COVID-19 pandemic demands joint interventions for the suppression of future waves.

Emerging evidence suggests a resurgence of COVID-19 in the coming years. It is thus critical to optimize emergency response planning from a broad, integrated perspective. We developed a mathematical model incorporating climate-driven variation in community transmissions and movement-modulated spatial diffusions of COVID-19 into various intervention scenarios. We find that an intensive 8-wk intervention targeting the reduction of local transmissibility and international travel is efficient and effective. Practically, we suggest a tiered implementation of this strategy where interventions are first implemented at locations in what we call the Global Intervention Hub, followed by timely interventions in secondary high-risk locations. We argue that thinking globally, categorizing locations in a hub-and-spoke intervention network, and acting locally, applying interventions at high-risk areas, is a functional strategy to avert the tremendous burden that would otherwise be placed on public health and society.

A Photoenzymatic Strategy for Radical-Mediated Stereoselective Hydroalkylation with Diazo Compounds.

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-stereogenic carbonyl compounds in good yields and stereoselectivities. This study further expands the possible reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.

Hybrid Catalyst Coupling Single-Atom Ni and Nanoscale Cu for Efficient CO2 Electroreduction to Ethylene.

A hybrid catalyst with integrated single-atom Ni and nanoscale Cu catalytic components is reported to enhance the C-C coupling and ethylene (C2H4) production efficiency in the electrocatalytic CO2 reduction reaction (eCO2RR). The single-atom Ni anchored on high-surface-area ordered mesoporous carbon enables high-rate and selective conversion of CO2 to CO in a wide potential range, which complements the subsequent CO enrichment on Cu nanowires (NWs) for the C-C coupling to C2H4. In situ surface-enhanced infrared absorption spectroscopy (SEIRAS) confirms the substantially improved CO enrichment on Cu, once the incorporation of single-atom Ni occurs. Also, in situ X-ray absorption near-edge structure (XANES) demonstrates the structural stability of the hybrid catalyst during eCO2RR. By modulating hybrid compositions, the optimized catalyst shows 66% Faradaic efficiency (FE) in an alkaline flow cell with over 100 mA·cm-2 at -0.5 V versus reversible hydrogen electrode, leading to a five-order enhancement in C2H4 selectivity compared with single-component Cu NWs.

Enantioselective Dearomative [3 + 2] Umpolung Annulation of N-Heteroarenes with Alkynes.

Enantioselective [3 + 2] annulation of N-heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient N-heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed. This protocol provides a straightforward access to a variety of N-spiroheterocyclic molecules in excellent enantioselectivities (76 examples, up to 99% ee).

Size-Controlled Nanoparticles Embedded in a Mesoporous Architecture Leading to Efficient and Selective Hydrogenolysis of Polyolefins.

A catalytic architecture, comprising a mesoporous silica shell surrounding platinum nanoparticles (NPs) supported on a solid silica sphere (mSiO2/Pt-X/SiO2; X is the mean NP diameter), catalyzes hydrogenolysis of melt-phase polyethylene (PE) into a narrow C23-centered distribution of hydrocarbons in high yield using very low Pt loadings (∼10-5 g Pt/g PE). During catalysis, a polymer chain enters a pore and contacts a Pt NP where the C-C bond cleavage occurs and then the smaller fragment exits the pore. mSiO2/Pt/SiO2 resists sintering or leaching of Pt and provides high yields of liquids; however, many structural and chemical effects on catalysis are not yet resolved. Here, we report the effects of Pt NP size on activity and selectivity in PE hydrogenolysis. Time-dependent conversion and yields and a lumped kinetics model based on the competitive adsorption of long vs short chains reveal that the activity of catalytic material is highest with the smallest NPs, consistent with a structure-sensitive reaction. Remarkably, the three mSiO2/Pt-X/SiO2 catalysts give equivalent selectivity. We propose that mesoscale pores in the catalytic architecture template the C23-centered distribution, whereas the active Pt sites influence the carbon-carbon bond cleavage rate. This conclusion provides a framework for catalyst design by separating the C-C bond cleavage activity at catalytic sites from selectivity for chain lengths of the products influenced by the structure of the catalytic architecture. The increased activity, selectivity, efficiency, and lifetime obtained using this architecture highlight the benefits of localized and confined environments for isolated catalytic particles under condensed-phase reaction conditions.

Fluorescence Anisotropy as a Self-Referencing Readout for Ion-Selective Sensing and Imaging Using Homo-FRET between Chromoionophores.

Fluorescence anisotropy has been widely used in developing biosensors and immunoassays, by virtue of the self-reference and environment-sensitive properties. However, fluorescence anisotropic chemical sensors on inorganic ions are limited by the total anisotropy change. To this end, we demonstrate here fluorescence anisotropic ion-selective optodes based on the homo-FRET (Förster resonance energy transfer) of the crowded chromoionophores. The conventional fluorescence on-off mode is transformed into the anisotropic mode. Variation of the target ion concentration changes the inter-chromoionophore distance in the organic sensing phase, leading to different extents of homo-FRET and steady-state anisotropy. A theoretical model is developed by coupling homo-FRET and anisotropy. Anisotropic detections of pH, K+, and Na+ are demonstrated as examples based on the different ionophores for H+, K+, and Na+, respectively. Further, fluorescence imaging of the nano-optodes, plasticized poly(vinyl chloride) sensing films, and live cells are demonstrated using a homemade fluorescence anisotropic imaging platform. The results form the basis of an ion-selective analytical method operating in the fluorescence anisotropic mode, which could potentially be applied to other fluorescence on-off probes based on homo-FRET.

MXene-Supported, Atomic-Layered Iridium Catalysts Created by Nanoparticle Re-Dispersion for Efficient Alkaline Hydrogen Evolution.

Tailoring the structure of metal components and interaction with their anchored substrates is essential for improving the catalytic performance of supported metal catalysts; the ideal catalytic configuration, especially down to the range of atomic layers, clusters, and even single atoms, remains a subject under intensive study. Here, an Ir-on-MXene (Mo2 TiC2 Tx ) catalyst with controlled morphology changing from nanoparticles down to flattened atomic layers, and finally ultrathin layers and single atoms dispersed on MXene nanosheets at elevated temperature, is presented. The intermediate structure, consisting of mostly Ir atomic layers, shows the highest activity toward the hydrogen evolution reaction (HER) under industry-compatible alkaline conditions. In addition, the better HER activity of Ir atomic layers than that of single atoms suggests that the former serves as the main active sites. Detailed mechanism analysis reveals that the nanoparticle re-dispersion process and Ir atomic layers with a moderate interaction to the substrate associate with unconventional electron transfer from MXene to Ir, leading to suitable H* adsorption. The results indicate that the structural design is important for the development of highly efficient catalysts.