Browse Articles

Reduction Inverts the Thermodynamics of the Stone–Wales Rearrangement

Abstract We demonstrate that alkali-metal doping of polycyclic aromatic hydrocarbons can reshape the potential energy surface in favor of an isomer that is disfavored in the neutral state. This effect enables an efficient inverse Stone–Wales rearrangement at temperatures as low as 250 °C for potassium-, rubidium-, and cesium-doped systems. In contrast, lithium and sodium doping exclusively promote cyclodehydrogenation at cove regions. Supported by density functional theory, we propose a mechanistically consistent pathway and report the isolation and characterization of key anionic intermediates by single-crystal X-ray diffraction, UV–vis spectroscopy, and magnetometry. These findings highlight how reduction can unlock otherwise inaccessible rearrangements in aromatic systems and inform our understanding of the functionalization of graphene, carbon nanotubes, and fullerenes.

Wide-angle multiplexed holographic photovoltaic concentrators recorded in a green photopolymer

Scope of Ni(II)-Catalyzed Nonalternating Ethylene/Carbon Monoxide Copolymerization

Abstract The recent achievement of a nonalternating ethylene/carbon monoxide (CO) copolymerization was a long-sought breakthrough. Their in-chain keto functional groups endow the resulting polyethylenes (keto-PEs) with photodegradability. To date, only two types of catalysts, based on long-known structural motifs, are capable of this challenging copolymerization to keto-PE materials, raising the question whether the reaction is restricted to this narrow scope. Here, we report a diverse range of neutral Ni(II) complexes provides access to keto-PEs, including a phosphine imidate Ni(II) catalyst that is competitive with state-of-the-art catalysts and a N-heterocyclic-carbene (NHC) phenolate Ni(II) catalyst with exceptional preference for ethylene vs CO incorporation. Density functional theory (DFT) calculations rationalize the observed selectivity for nonalternating and alternating chain growth from the individual catalysts’ activation barrier differences ΔΔG‡ and identify the strong trans-effect of the [NHC,O]-ligand and its high steric hindrance as origins of the desirable exceptionally low preference for CO incorporation.

Notch-1 suppressed ocular trauma injury in ganglion cells via modulating NICD/YAP/EZH2 signaling induced ferroptosis

Electrochemical Nitrate Reduction with Low-Index Cu Single Crystals: Selectivity Trends in Alkaline Solution

Abstract Electrochemical nitrate (NO3−) reduction is a promising pathway toward the production of ammonia (NH3). While copper (Cu) electrodes are commonly used for this reaction, the influence of Cu surface structure on reaction selectivity is poorly understood. Here, we performed electrochemical NO3− reduction in alkaline electrolytes with Cu(100), Cu(110), and Cu(111) single-crystal electrodes and quantified the product distributions across a range of applied potentials. Our systematic study of electrocatalytic NO3− reduction demonstrated that the Cu(100) and Cu(110) surfaces exhibited similar selectivity and rates for NH3 production, but the Cu(100) surface provided >95% Faradaic efficiency toward NH3 over the broadest range of applied potentials. In contrast, the Cu(111) surface was significantly less selective for NH3 production. Further comparing the electrochemical behavior of Cu single crystals to their corresponding product distributions revealed that nitrite (NO2−) reduction voltammograms were strong predictors of electrocatalytic performance for all three low-index Cu surfaces in alkaline electrolytes. Quantum mechanical calculations indicate that the Cu(100) surface exhibits the lowest potential-determining step for NO3− reduction to NH3, supporting our experimental findings. Detailed analysis of metal−adsorbate interactions also revealed the role of Cu surface structure in stabilizing key reaction intermediates to promote selective NH3 production. Our combined experimental and computational study establishes electrocatalytic selectivity of low-index Cu facets for NH3 synthesis and offers practical guidelines for the design of Cu-based electrocatalysts capable of selective electrochemical NO3− reduction in alkaline solutions.

Effects of midsole support plate material on lower-limb kinetics and muscle activation during basketball-specific movements

Two Mechanisms One Molecule: Developing a ‘Truly’ Bifunctional Degrader Targeting Rpn13 and CRBN

Abstract Targeted protein degradation (TPD) has emerged as a powerful strategy to eliminate disease-relevant proteins, yet current approaches remain largely constrained to hijacking ubiquitin ligases. We previously introduced ByeTACs, bifunctional molecules that directly recruit proteins to the proteasome for E-ligase independent degradation. Here, we report “Truly” degraders, a new class of dual-mechanism molecules that combine a ligand for the proteasomal receptor Rpn13 with a ligand for cereblon (CRBN) to simultaneously engage both ubiquitin-independent and ubiquitin-dependent degradation pathways. Structure-guided design identified an optimal linker length that supports efficient substrate processing, with the PEG4 derivative (Truly-4) inducing robust depletion of both Rpn13 and CRBN in several cancer cell types. Remarkably, Truly-4 is the first noncovalent small molecule shown to degrade full-length Rpn13, a target previously approached using covalent or domain-restricted strategies. Mechanistic studies confirmed that degradation of Rpn13 proceeds via CRBN-dependent E3 ligase activity, whereas CRBN degradation occurs through an E-ligase independent process, consistent with a ByeTAC mechanism. Importantly, Truly-4 induces selective cytotoxicity in hematologic and solid cancer cell lines but not in healthy cells, despite comparable Rpn13 depletion, indicating that dual degradation can uncouple target engagement from toxicity. These findings establish a generalizable framework for engineering bifunctional degraders that program the proteasome to execute parallel degradation mechanisms and highlight proteasome receptors as druggable nodes for selective destruction of disease-relevant proteins.

A hybrid signal-dynamics health index fusion framework for prognostics of small-scale wind turbine blades

Influence of Primary Coordination Sphere on Anion Rebound Selectivity in Nonheme Fe Enzyme-Catalyzed C(sp3)–H Functionalization: A Comparative Experimental and Computational Study of EgtB and ACCO

Abstract Developing enzymatic mechanisms for C–F bond formation remains a long-standing challenge. Here, we repurposed the biosynthetic nonheme Fe enzyme EgtB, which features a three-histidine facial triad, to catalyze C(sp3)–H fluorination reactions. Directed evolution of EgtB afforded two new-to-nature fluorine atom transferases with opposite enantiopreference, EgtBCHF1 and EgtBCHF2, with up to 28-fold improved total activity. In contrast to our previously evolved nonheme Fe fluorine atom transfer biocatalyst ACCOCHF, which contains a two-histidine-one-carboxylate facial triad, the evolved EgtBCHF variants displayed unexpected hydroxylation activity. 18O-labeling experiments showed that the hydroxy group originated from water rather than residual O2. Computational studies suggested that the three-histidine-supported Fe(III) center exhibits enhanced Lewis acidity compared to the two-histidine-one-carboxylate system, allowing deprotonation of Fe(III)-bound water to form a Fe(III)–OH species that catalyzes radical hydroxylation. Primary coordination-sphere mutagenesis in EgtB and ACCO further supported the critical role of Fe coordination chemistry in controlling radical rebound reactivity and selectivity. Computational studies revealed that Fe coordination chemistry strongly influences both fluorine atom abstraction and radical rebound, with the intrinsic C–X (X = F, OH, and N3) bond forming radical rebound preference following the order N3 > OH > F. Furthermore, multivariate linear regression analysis revealed that fluorine atom abstraction is primarily governed by the intrinsic Fe–F bond strength, whereas fluorine rebound is predominantly controlled by the electronic structure of the Fe(III) intermediate. Together, these findings provide mechanistic insights into nonheme Fe enzymology and reprogramming toward selective radical rebound reactions, including challenging C–H fluorination.

Cardiovascular disease prediction using variational recurrent autoencoders with uncertainty estimation

Effect of Sm-doping on structural, visible-light activated photocatalytic degradation of crystal violet dye and antifungal activity of ZnO nanoparticles

Bidirectional Chemo-Mechanical Interface Stabilization in Perovskite Solar Cells

Abstract The interface structures between dissimilar layers in perovskite solar cells (PSCs) are prone to the concurrent occurrence of lateral (in-plane) chemical aggregation and vertical (out-of-plane) mechanical delamination. This issue severely affects long-term optoelectronic processes in PSCs, and it has not been addressed holistically. Herein, we introduce an ultrathin interfacial layer of 1,3,6,8-pyrenetetrasulfonic tetrasodium salt (PTS) to stabilize the perovskite/C60 interface at the molecular level. The sulfonate groups in PTS molecules anchor to the perovskite interface, while the parallelly aligned pyrene cores establish robust π–π interactions with C60 molecules. The reconstructed interface enhances the interfacial adhesion and restricts the mobility of C60 molecules, enabling a bidirectional chemo-mechanical interface stabilization (BCIS) mechanism at the perovskite/C60 interface. The resultant PSCs deliver power conversion efficiencies (PCEs) of up to 26.53%, showing 96% PCE retention after 1,000 h maximum-power-point tracking (ISOS-L-1l), and 91% PCE retention after 300 thermal cycles (−40 to 85 °C, IEC61215 MQT11). The scalability of PTS treatment is demonstrated by the 818 cm2 (aperture area) perovskite solar modules (PSMs) with PCEs over 20% using industrial-compatible manufacturing processes under 55% relative humidity (RH). This work underscores bidirectional interface engineering as a critical strategy for advancing commercially viable perovskite photovoltaics.

Extraction and chemical characterization of natural dye from western himalayan wild pomegranate peel for textile applications

Role of Coordination Environment in Synergistic Catalysis: A Molecular Orbital Perspective on M1M2N6 Catalysts

Abstract Visualizing the coordination environment-dependent synergistic mechanisms that govern the structural stability and adsorption behavior of dual-atom catalysts (DACs) is pivotal for precise catalyst design. However, insights into these mechanisms at the molecular orbital level remain elusive. Herein, we present large-scale density functional theory calculations to elucidate how synergistic effects arise from the combination of d atomic orbitals into molecular orbitals between M1 and M2 sites, with notable variations observed from M1–N3–M2–N3–C to M1–N4–M2–N4–C. We identify an average weakening of M1/M2–N bond strength in M1–N3–M2–N3–C relative to M1–N4–M2–N4–C, which is attributed to a shift from direct dx2–y2 orbital overlap to nitrogen-mediated interactions involving the hybridization of bridge nitrogen 2p orbitals. Using hydrogen as a model adsorbate, we demonstrate that hydrogen adsorption on M1–N3–M2–N3–C shifts from wild modulation via a bridge configuration to mild modulation through an end-on configuration, signifying a selective orbital coupling from dx2–y2 to dz2 orbitals. In contrast, hydrogen adsorption on M1–N4–M2–N4–C exhibits only mild modulation via an end-on configuration. This behavior is ascribed to the symmetry constraints of antibonding (d-d/d*)-p* molecular orbitals near the Fermi level, mediated by nitrogen-mediated dz2-dz2* molecular orbitals. Furthermore, machine learning analyses corroborate these coordination environment-dependent synergistic mechanisms. Our findings provide a comprehensive molecular orbital-level understanding of how the interplay between coordination environments and electronic structures influences the properties of M1M2N6 catalysts, thereby establishing a theoretical framework for enhanced DACs design.

Scalable prediction of local road traffic volume via macro-level indicators and spatial heterogeneity modeling

Pd/Mo-Catalyzed <i>ortho</i> -Dihydroxylation of Aromatic Rings: Dual-Metal-Mediated C(sp2)–H Functionalization

Abstract We report a direct ortho-dihydroxylation protocol of benzoic acids using a Pd/Mo bimetallic catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant. The Mo component significantly promotes the dihydroxylation reaction, especially the second hydroxylation step, by boosting the oxidative capacity of TBHP and presumably facilitating the oxidative addition process of Pd–Ar σ-intermediate. Mechanistic studies, including radical inhibition experiments, spectroscopic analyses, and substituent effect evaluations, reveal that Mo most likely facilitates the conventional Pd-catalyzed pathway by introducing a radical-generating step. Notably, this dual-metal-mediated method can be readily tuned to afford monohydroxylation products by simply reducing the amount of TBHP. Gram-scale reactions and subsequent derivatizations further confirm the practicality of this method. Since the directing carboxyl group can be easily removed via catalytic or thermal decarboxylation, this Pd/Mo bimetallic catalytic system offers a concise synthetic route to meta-diphenolic compounds, the vital fine chemicals conventionally synthesized via multistep industrial processes.

Benchmarking machine learning and deep learning models with a novel graph-attention SAGEConv-transformer for ECG arrhythmia detection

Accounting for spatial and environmental sampling bias in a species distribution model of Aedes vexans (Diptera: Culicidae)

Abstract This study evaluates the potential of species distribution models to predict habitat suitability for the floodplain mosquito Aedes vexans , with a particular focus on ephemeral breeding habitats such as flood-prone areas. These habitats are essential for oviposition, yet have not been explicitly incorporated as predictors in existing modelling approaches. Flood hazard was included as an environmental predictor to represent the species’ dependence on transient water bodies. However, initial model runs showed only a marginal contribution of this predictor to overall model performance. We demonstrate that this weak contribution was not due to the ecological irrelevance of ephemeral habitats, but instead resulted from strong sampling biases in the occurrence data, which were predominantly concentrated in urban environments. To address this issue, we applied spatial thinning and environmental filtering to reduce spatial clustering and the overrepresentation of environmentally similar regions. Using Maxent, we compared candidate models with and without bias correction across multiple environmentally stratified test datasets. Our results show that correcting for sampling bias improved model accuracy more than the inclusion of an additional habitat-relevant predictor alone. The final model produced more reliable suitability predictions, particularly in flood-prone and previously under-sampled areas.

An activity–resistance trade-off constrains enzyme evolution

The presence of self-resistance genes in antibiotic-producing organisms poses a paradox: How can resistance evolve before the antibiotic exists, and how can an antibiotic producer arise without first evolving resistance? Here, we examine the evolutionary origins of self-resistance to mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase (IMPDH). The MPA biosynthetic gene cluster (BGC) includes a resistant IMPDH-B. Homologs of IMPDH-B occur not only in MPA producers but also in many nonproducing fungi, where remnants of the MPA BGC remain detectable. The phylogeny of IMPDH-B is incongruent with the fungal species tree, consistent with multiple horizontal gene transfer events between Aspergillus and Sordariomycetes. We characterized eleven extant IMPDH-Bs, five from MPA producers and six from nonproducers, along with seven resurrected ancestral enzymes (Anc1–Anc7). MPA resistance appeared between Anc2 and Anc3 and coincided with a loss of catalytic efficiency. Across both ancestral and extant enzymes, MPA resistance correlated strongly with reduced activity, revealing a robust activity–resistance trade-off that has persisted for millions of years. Unexpectedly, both the IMPDH-Bs and ancestral enzymes Anc3–Anc7 were also resistant to ribavirin-5′-monophosphate (RVP), an IMP-competitive inhibitor. Because MPA and RVP bind to similar enzyme conformations, the activity–resistance trade-off may reflect a design constraint imposed by the need to maintain resistance to multiple inhibitors. Intriguingly, although Anc1 and Anc2 are equally sensitive to MPA, Anc2 shows reduced susceptibility to RVP. This pattern suggests that preexisting resistance to another IMPDH inhibitor may have created a permissive background for the later evolution of MPA biosynthesis.

Association between ABO and Rh blood groups and subtypes of age-related macular degeneration: A cross-sectional study

Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment and is driven by complex genetic, inflammatory, and vascular mechanisms. ABO and Rh blood group antigens, which are expressed on vascular endothelium and involved in immune and hemostatic pathways, have been implicated in various systemic diseases; however, their potential association with AMD phenotypic variation remains unclear. In this cross-sectional study, 488 patients with clinically confirmed AMD from a tertiary referral center were included. AMD was classified as neovascular AMD (wet AMD) or nonneovascular AMD (dry AMD) based on multimodal imaging and standardized diagnostic criteria. ABO and Rh blood group data were obtained from medical records, and individuals with major known AMD risk factors, including smoking, alcohol consumption, and obesity, were excluded to reduce confounding. Associations between AMD subtypes and ABO blood groups and Rh factor were evaluated using the Pearson chi-square test, and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The mean age of participants was 66.9 ± 4.7 years, and 273 patients (55.9%) had neovascular AMD. A statistically significant association was observed between ABO blood group distribution and AMD subtypes (χ² = 8.31, p = 0.040). A higher proportion of patients with neovascular AMD had blood group A, whereas blood group B was relatively more common among patients with nonneovascular AMD. However, individual pairwise crude odds ratio analyses did not demonstrate statistically significant associations for specific ABO blood groups. No association was observed for Rh status. These findings suggest a possible modest association between overall ABO blood group distribution and AMD phenotype; however, the clinical significance of this relationship remains uncertain, particularly in the absence of multivariable adjustment. Larger multicenter studies with comprehensive multivariable analyses are warranted.