Understanding how grain boundaries mediate fracture remains a critical challenge in designing ductile, high-performance refractory alloys. Here, we extend the Rice-Thomson criterion to account for the angle between cracks and the impinging grain boundaries (GBs), capturing the competition between intergranular fracture and dislocation-mediated plasticity. Using machine learning interatomic potentials, we performed molecular statics simulations to probe fracture mechanisms in nanocrystalline NbMoTaW and Nb₄₅Ta₂₅Ti₁₅Hf₁₅, each with two different grain sizes, revealing trends consistent with experimental observations and the extended Rice model. Comparison with averaged R-curves for bulk samples demonstrates that GBs enhance ductility in Nb₄₅Ta₂₅Ti₁₅Hf₁₅ in both grain sizes investigated. In contrast, GBs only locally improve fracture resistance in NbMoTaW when cracks are temporarily pinned at GBs inclined at high angles from the crack, but generally promote brittle intergranular fracture. These contrasting behaviors are attributed to differences in GB cohesion, reflecting clear alloying trends that align with ab-initio calculations and trends observed experimentally. Our results bridge classical fracture theory, atomistic simulations, and experimental observations, providing a comprehensive understanding of the fracture mechanisms in nanocrystalline refractory complex concentrated alloys.

In this work, we assess the accuracy of the approximate fourth-order N-electron valence perturbation theory (NEVPT4(SD)) methodology for computing excited states of organic molecules. The well-established Thiel benchmark set was employed, comprising 225 vertical excitations spanning π → π*, <i>n</i> → π*, and σ → π* transition types. A state-specific canonicalization procedure was applied, enabling a direct comparison with CC3 reference data reported by Schreiber et al. <i>J. Chem. Phys.</i>, <b>2008</b>, <i>128</i>, 134110. For both singlet and triplet excitations, NEVPT4(SD) systematically outperforms lower-order NEVPT variants, as well as previously reported complete active space second-order perturbation theory (CASPT2) results. A detailed analysis of the singlet excitations reveals that <i>n</i> → π* transitions have a slight tendency to be overestimated (by about 0.1 eV), while π → π* excitations tend to be slightly underestimated (by -0.04 eV). While this shift persists across all NEVPT perturbation orders, its magnitude decreases with higher-order treatments. Across the entire test set, NEVPT4(SD) has a very narrow error distribution with a peak very close to 0. Thus, this study demonstrates the robustness and high accuracy of NEVPT4(SD) for vertical excitation energies, highlighting its clear advantages over lower-order perturbative approaches while remaining computationally much more affordable than other multireference correlation approaches that proceed beyond second-order perturbation theory.

ABSTRACT The design of lightweight, high‐strength, and tough composites is crucial for enhancing the mechanical properties of materials. Bio‐inspired designs for brick‐and‐mortar structures can considerably enhance the strength and durability of composites. Phase interfaces are especially important, as material failures often occur at these interfaces, leading to substantial degradation in structural performance. Accordingly, building robust interfacial connections poses a crucial challenge. In this study, a ceramic‐metal bulk composite with an ordered alternating layered structure, measuring 30 mm × 30 mm × 30 mm, is fabricated by infiltrating 6061 aluminum alloy into an alumina skeleton. Using pressure infiltration technique, a robust interface is formed by constructing a valence gradient of aluminum at the interface between the alumina and the aluminum alloy layers. Benefiting from the synergistic effects of lamellar reinforcement and valence gradient interfacial reinforcement, the ceramic‐metal composite exhibits excellent properties, including high flexural strength (∼986.4 MPa) and toughness (∼45.3 MPa·m 1/2 ) as well as a low thermal expansion coefficient of ∼6.6 × 10 −6 K −1 . The valence gradient interface design strategy is also applicable to ceramic‐metal composite systems with identical elements, such as MgO‐Mg, offering a new pathway for the structural design of advanced composites.

Reinforcement learning with verifiable rewards has become a common way to improve explicit reasoning in large language models, but final-answer correctness alone does not reveal whether the reasoning trace is faithful, reliable, or useful to the model that consumes it. This outcome-only signal can reinforce traces that are right for the wrong reasons, overstate reasoning gains by rewarding shortcuts, and propagate flawed intermediate states in multi-step systems. To this end, we propose TraceLift, a planner-executor training framework that treats reasoning as a consumable intermediate artifact. During planner training, the planner emits tagged reasoning. A frozen executor turns this reasoning into the final artifact for verifier feedback, while an executor-grounded reward shapes the intermediate trace. This reward multiplies a rubric-based Reasoning Reward Model (RM) score by measured uplift on the same frozen executor, crediting traces that are both high-quality and useful. To make reasoning quality directly learnable, we introduce TRACELIFT-GROUPS, a rubric-annotated reason-only dataset built from math and code seed problems. Each example is a same-problem group containing a high-quality reference trace and multiple plausible flawed traces with localized perturbations that reduce reasoning quality or solution support while preserving task relevance. Extensive experiments on code and math benchmarks show that this executor-grounded reasoning reward improves the two-stage planner-executor system over execution-only training, suggesting that reasoning supervision should evaluate not only whether a trace looks good, but also whether it helps the model that consumes it. Our code is available at: https://github.com/MasaiahHan/TraceLift

Emerging evidence suggests that alterations in immunometabolism contribute to pathogenesis of inflammatory diseases, providing potential therapeutic targets. Anti-inflammatory drugs such as glucocorticoids, metformin, and dimethyl fumarate (DMF) modulate key immunometabolic pathways. Glucocorticoids boost itaconate production, which exerts anti-inflammatory effects via multiple targets, including by modification of cysteines on inflammatory proteins. Metformin, known for inhibiting gluconeogenesis in type 2 diabetes, also blocks mitochondrial Complex I and increases GDF-15, a regulator of food intake with anti-inflammatory properties, which may explain effects of metformin on inflammation. DMF, like itaconate, modifies cysteines on target proteins, notably KEAP1, leading to Nrf2 activation, which induces antioxidant enzymes and suppresses inflammatory gene expression. These immunometabolic actions suggest that targeting immune cell metabolism could provide new strategies for treating autoimmune diseases. This review explores recent advances in itaconate, GDF-15, and Nrf2 signaling and how harnessing these pathways may lead to novel anti-inflammatory therapies for patients with inflammatory diseases.

El tratamiento quirúrgico del cáncer de mama ha evolucionado, desde cirugías radicales que incluían la pared torácica hasta cirugías conservadoras de resección tumoral con margen oncológico seguro complementadas con radioterapia; estas se consideran alternativa a la cirugía radical. La supervivencia es similar en ambos procedimientos. Metodología: Estudio de cohorte retrospectivo que evaluó las características demográficas, patológicas y desenlaces clínicos, como recaída y mortalidad, en mujeres con cáncer invasivo, sometidas a cirugía conservadora entre 1998 y 2007 en el INC. Resultados: Se incluyeron 358 pacientes con edad promedio de 53 anos y estados tumora- ˜ les tempranos en su mayoría. Con mediana de seguimiento de cuatro anos se presentaron 40 ˜ recaídas entre locales, regionales y sistémicas con una tasa de recaída de 2,6 recaídas por 100 pacientes/ano. Se presentó un mayor porcentaje de recaídas en estado clínico avanzado ˜ (p=0,022), tamano tumoral mayor de 2 centímetros (p=0,02 ˜ ) y a mayor número de ganglios comprometidos en el vaciamiento axilar (p=0,004). La tasa de mortalidad fue 1,2 muertes por 100 pacientes/ano. Los márgenes positivos se relacionaron con estado clínico avanzado (p=0,010) ˜ y las pacientes con márgenes positivos que recibieron manejo no quirúrgico presentaron un porcentaje mayor de recaída, comparado con las llevadas a cirugía (p=0,023). Esta diferencia se conservó al comparar manejo quirúrgico con no quirúrgico en márgenes positivos invasivos (p=0,037). Conclusiones: El estado clínico avanzado, se relacionó con márgenes positivos y recaída tumoral. El compromiso ganglionar axilar y el manejo no quirúrgico de los márgenes positivos determinaron un mayor porcentaje de recaída.

In this work, the formal development and implementation of a general restricted open-shell Hartree-Fock (g-ROHF) response theory is presented. The theory enables analytic computation of electric and magnetic response properties for arbitrarily complex open-shell configurations. In contrast to traditional ROHF methods, which are typically restricted to high-spin cases, the g-ROHF formulation supports general-spin couplings and orbital degeneracies while preserving the spin purity. A new set of vector-coupling coefficients is introduced that allows for the calculation of a proper spin density from a g-ROHF wave function. Analytic nuclear derivatives, along with the electric and magnetic orbital Hessians, are derived in a unified framework. Special attention is given to the treatment of SCF instabilities and the projection of unphysical modes from the response space. An efficient AO-driven implementation is described and validated across a broad range of open-shell systems, including small molecules, transition-metal complexes, and metal-radical assemblies. Specifically, the method is applied to the calculation of g-tensors and hyperfine couplings (including spin-orbit coupling corrections) in experimentally well-characterized systems such as mixed-valence manganese(III/IV) dimers and the metal-radical complex Fe(GMA)(pyridine)⁺. The g-ROHF framework provides a robust, efficient, and physically rigorous platform for treating the electronic structure and properties of complex open-shell molecules and serves as a convenient foundation for the development of post-Hartree-Fock correlation methods. The present work sets the stage for extensions to excited-state response theory, DFT-based treatments, and coupled-cluster response formulations.

Herein, we report a straightforward methodology for direct deaminative cyanation of anilines via aryl diazonium salts as fleeting intermediates. The approach leverages the kinetic stability of nitrate and copper cyanide, iron's ability to facilitate nitrate reduction, and appropriate relative rates to ensure the product-forming kinetic reaction pathway despite several thermodynamically favored, undesired reactions. We present insight into the previously unappreciated nitrate reduction mechanism by simple sulfur-based reductants, such as SO₂. The oxylanion radical transfer mechanism is rarely encountered in synthetic chemistry but has ample precedent in biology and could provide a general, useful strategy for chemical nitrate reduction.

Off-line analysis software in engineering safety assessment system has been developed in the rapid development of domestic dam safety automatic monitoring technique.The function and composition of the software have been introduced.The software has already been applied to an actual project and the result shows that it can make safety monitoring information function timely and effectively to provide reference and decision support for the project operation safety.

One remarkable feature of catalysis in chemical synthesis is its capacity to override substrate-imposed reactivity and selectivity. The inversion of normal reaction patterns, commonly known as Umpolung, can be divided into (1) functional group Umpolung, where electrophilic groups are rendered nucleophilic (or vice versa), and (2) pericyclic Umpolung, in which the regioselectivity of pericyclic reactions is reversed relative to the predictions of frontier molecular orbital (FMO) theory. Although catalytic functional group Umpolung has been extensively investigated, the highly organized, concerted nature of pericyclic reactions makes inverting their conventional regioselectivity particularly challenging. To date, such inversion has been achieved only using engineered substrates or near-stoichiometric amounts of molecular cages. Here, we report an example of a chiral confined acid-catalyzed, asymmetric Umpolung of the Diels-Alder reaction. In our system, tropone reacts with enol ethers to deliver "contra-FMO" products with high yield, stereoselectivity, and regioselectivity. Mechanistic and computational studies indicate that a network of attractive noncovalent interactions, including π-π-interactions, nonclassical hydrogen bonding, and dispersion, governs the inverted regioselectivity. We anticipate that confined acid catalysis will open new avenues for addressing challenges in pericyclic Umpolung and regioselectivity control.

The use of neuroprotective nutraceuticals as a strategy against neurodegenerative diseases such as Parkinson’s disease (PD) has gained considerable traction in recent years. In this review, we highlight ergothioneine (ET)—a naturally occurring thiol/thione derivative abundant in mushrooms—as a promising candidate, given its long half-life, blood–brain barrier penetration, and high bioavailability. Numerous population studies have linked low blood ET levels with increased risk and progression of neurological and other age-related disorders in humans, suggesting that dietary ET may confer neuroprotective benefits. Supporting this, several studies have demonstrated the efficacy of ET treatment in reducing PD-associated molecular damage across various pre-clinical models such as C. elegans, Drosophila, rodent models and human neuronal cultures, leading to marked improvements in disease phenotypes. Here, we summarize some of the proposed mechanisms by which ET may exert neuroprotection in PD, including the reduction of protein aggregation, enhancement of mitochondrial function, mitigation of oxidative stress, and attenuation of apoptosis and neuroinflammation. We also highlight recent clinical trials demonstrating the safety and potential efficacy of ET and propose future research to facilitate the translation of ET into the clinic.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO₃, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye. These findings identify a strong association between low ET levels and AMD, warranting further studies to determine whether ET supplementation can modify AMD risk or progression.