The synergistic removal of NO and chlorinated volatile organic compounds (CVOCs) using bifunctional catalysts has emerged as a cutting-edge strategy in environmental catalysis. However, achieving both efficient NOx selective catalytic reduction and CVOCs catalytic oxidation remains fundamentally challenging due to the inherent trade-off between activity and selectivity. Herein, we demonstrate that this trade-off can be overcome by applying a mechanochemical strategy coupled with electronic band modulation to construct a novel heterojunction catalyst, in which MnCe oxides are integrated with piezoelectric BaTiO3 to form a heterojunction interface. The optimized TB-MnCe catalyst exhibits remarkable synergistic performance, achieving the synergistic removal of o-dichlorobenzene (>80%) and NOx (100%) within a broad temperature range of 250-350 °C. Combined experimental and theoretical investigations reveal an interfacial charge transfer of approximately 4.6 electrons from BaTiO3 to MnCe during mechanochemical treatment. This charge redistribution, mediated by the engineered interface, significantly enhances the redox capability of the active sites and promotes cooperative reactions. This work highlights that atomic-level interfacial electronic modulation induced by mechanochemical processing provides a powerful route to resolve the activity-selectivity dilemma in bifunctional catalysis.
Neuroendovascular venous interventions are increasingly performed using technologies originally developed for arterial procedures and indications. However, the major dural venous sinuses possess a unique intraluminal anatomy that is not present in arteries, raising concerns about device-anatomy interactions that may affect procedural performance. We used a perfused human cadaveric model with direct intraluminal angioscopic visualization to evaluate currently available endovascular devices within the dural venous sinuses and to characterize mechanisms of device-anatomy interactions associated with technical difficulty and failure. Six fresh human head-and-neck cadaveric specimens were perfused with 0.9% saline solution via bilateral internal jugular vein catheterization using a peristaltic pump. Direct intraluminal angioscopic visualization was achieved through transcranial access to the major dural venous sinuses, allowing real-time observation of target segments during device manipulation. Standard endovascular maneuvers were performed within the dural venous sinuses, including guidewire and microcatheter navigation, catheter advancement, venous stent deployment, stent retriever deployment, aspiration thrombectomy, and balloon angioplasty. Angioscopic and fluoroscopic recordings were independently reviewed by experienced neurointerventionists to identify and categorize technical challenges and failure mechanisms. Angioscopy revealed multiple device-intraluminal interactions that were not fully appreciated on fluoroscopy alone. Several representative technical challenge and failure scenarios were identified and grouped into four principal mechanisms: (1) catheterization of venous channels parallel to the main sinus lumen, resulting in catheter entrapment and incomplete expansion of venous stents and stent retrievers; (2) device deformation or incomplete expansion due to intraluminal bands, including stent deformation, malposition, and constrained balloon angioplasty; (3) arrested or impaired device advancement caused by intraluminal bands, frequently necessitating microcatheter-assisted support to overcome ledge effects; and (4) interaction with arachnoid granulations leading to occlusion of aspiration catheter inlets and impeded intraluminal navigation. The venous system differs fundamentally from arteries in luminal geometry and internal architecture. Our findings demonstrate that arterial-derived devices incompletely accommodate these differences, resulting in parallel channel navigation, constrained expansion and deformation of stents, and occlusion of suction catheters. These findings highlight the fact that veins are not arteries and underscore the need for venous-specific techniques and technologies.
This study investigates the geochemical dynamics and ecological risks of rare earth elements (REE) in abandoned clay mining lakes in the second world's largest producer of ceramic tiles in Santa Gertrudes (CDSG), Brazil. Using a multi-technique approach, combining conventional filtration, diffusive gradients in thin films (DGT), single-particle inductively coupled mass spectrometry (spICP-MS), and geochemical modelling, a seasonal baseline was established and the influence of an atmospheric particulate deposition event associated with an unprecedent 2024 wildfire episode was evaluated. Results showed that seasonal variability produced relatively minor changes in REE behaviour, whereas the 2024 atmospheric deposition event promoted substantial shifts in REE partitioning. The median total concentration (∑REET) surged from 3,200 ng L-1 in 2022 to 25,800 ng L-1 during the 2024 event, with Cerium (Ce) reaching a peak of 12,500 ng L-1. A critical decoupling between fractions was observed: while the dissolved fraction (<0.45 μm) accounted for up to 82% of REEs in 2022, it dropped drastically to <1% in 2024, with DGT-measured lability largely varying across all campaigns. The detection of Ce-containing nanoparticles via spICP-MS (8.4×109 to 1.7×1010 Particles L-1), with a median size of ∼30 nm and an average mass of 0.13 fg, suggested relevant inorganic colloidal transport within the filtered fraction following the atmospheric deposition event. Geochemical signatures revealed persistent positive Cerium (Ce) Europium (Eu) anomalies of lithological origin. Although risk quotients (RQ) for the labile fraction decreased during the atmospheric deposition event due to low lability, the substantial increase in total REE burden suggests a transfer of ecological risk from the dissolved to the particulate phase. We conclude that conventional filtration overestimates REE bioavailability and that episodic atmospheric disturbances fundamentally alter the partitioning and fate of rare earth elements in freshwater systems.
Physics-Informed Neural Networks (PINNs) have emerged as a powerful framework for solving partial differential equations (PDEs) by embedding physical laws directly into the loss function. However, as a fundamental optimization issue, internal covariate shift (ICS) hinders the stable and effective training of PINNs by disrupting feature distributions and limiting model expressiveness. Conventional remedies for ICS-such as Batch Normalization and Layer Normalization-aim to stabilize feature distributions through statistical regularization. However, PINNs require deterministic coordinate-to-solution mappings for enforcing physical constraints, making such strategies fundamentally misaligned with their formulation. To address this issue, we propose Mask-PINNs, which introduce a smooth, learnable mask to adaptively regulate internal features without altering the pointwise physics-based formulation. We provide a theoretical analysis showing that the mask suppresses the expansion of feature representations through a carefully designed modulation mechanism. Empirically, we validate the method on multiple PDE benchmarks across diverse activation functions. Our results show consistent improvements in prediction accuracy, convergence stability, and robustness. Furthermore, we demonstrate that Mask-PINNs enable the effective use of wider networks, overcoming a key limitation in existing PINN frameworks. The codes of the experiments can be found on https://github.com/flongjiang/Mask-PINNs.
Physician Orders for Life-Sustaining Treatment (POLST) and Advance Directives (AD) aim to honor patient autonomy. However, the impact of the signatory's identity-whether the patient or a surrogate-on clinical trajectories in the intensive care unit (ICU) remains poorly characterized. To evaluate the association between signatory identity and terminal care intensity and hospitalization costs among adult patients in the ICU. This nationwide population-based cohort study utilized the South Korean National Health Insurance Service database, including 1,189,042 adult ICU admissions between 2020 and 2023. Statistical analyses employed high-dimensional fixed-effects models to account for institutional variability across 417 hospitals. Among 1,189,042 patients, surrogate-determined POLST (SD-POLST) was more than three times as prevalent as patient-determined POLST (PD-POLST). Among 90-day decedents, PD-POLST was associated with significantly reduced odds of invasive terminal care (OR, 0.43; 95% CI, 0.43-0.54). Conversely, SD-POLST more than doubled the odds (OR, 2.16; 95% CI, 1.98-2.35). Notably, even patients with proactive ADs experienced increased care intensity once a surrogate signed the final order (OR, 1.69; 95% CI, 1.51-1.89), indicating a phenomenon of "AD erosion." SD-POLST was also associated with significantly higher daily hospitalization costs (cost ratio, 1.04; 95% CI, 1.02-1.06) compared with no documentation. The clinical efficacy of POLST in limiting non-beneficial care depends fundamentally on the signatory. Surrogate-led decisions were associated with paradoxically higher care intensity and costs, potentially overriding prior patient wishes. These findings highlight the critical importance of early, patient-led discussions to ensure goal-concordant end-of-life care in the ICU.
ConspectusOrbital correlation diagrams are central to chemistry. Based on the symmetry compatibility and orbital overlap amplitude, they link the energy-ordered frontier molecular orbitals (MOs) of reactants and products and have long been a powerful and essential tool for understanding chemical interactions (reactions) and molecular properties. The frontier MOs typically include the highest occupied MOs (HOMOs) and the lowest unoccupied MOs (LUMOs), along with a few nearby orbitals of the reactants. However, it is also known that some reactions cannot be well explained with a few frontier MOs. The main drawback of traditional orbital correlation diagrams is that the orbital energies of the reactants shown in the diagram are calculated assuming they are in free, isolated states. But orbital energy levels can be significantly shifted by external fields and the existence of neighboring molecules. In other words, orbital energy levels can be notably reshuffled when we put reactants "physically" (via electrostatic interactions, Pauli repulsion, and van der Waals interactions) together, even without "chemical" interactions (via orbital mixtures or electron transfers).Here, we introduce a novel concept, "in situ" orbital correlation, and demonstrate its applications. This concept is based on our developed block-localized wave function (BLW), which is the simplest variant of ab initio valence bond (VB) theory. The uniqueness of the BLW method lies in its ability to derive orbital energies of a molecule self-consistently in the presence of other species or external fields, as a BLW solution essentially corresponds to a hypothetical diabatic (or resonance) state, a mathematical construct in which all electron transfers between interacting species are "disabled". In such a way, we can correlate orbitals by considering the field (physical) effects from neighboring species even without any orbital (chemical) interactions.This "in situ" orbital correlation concept was first proposed in the study of the activation mechanism of CO by the diboryne compound B2(NHCR)2, where we demonstrated that when CO approaches B2(NHCR)2, there is a HOMO-LUMO swap in B2(NHCR)2 primarily due to the Pauli repulsion from the carbon lone pair of CO, leading to the compatibility of HOMO and HOMO-1 of B2(NHCR)2 with both π* orbitals of CO. Since then, this concept has been adopted in much of our research. For instance, in our most recent study of NCCL- anions (L = N2, CO, CS), which exhibit notable geometric differences, "in situ" orbital correlation diagrams reveal an orbital swap in the fragment NCC- with the approach of the ligand L and subsequently confirm the C(0) theory proposed by the Frenking group. Previously, we explored the "anti-electrostatic" nature of the Al-Mg bond and confirmed that the bond is purely ionic. This contradicts the view from frontier orbitals of Al(I) and Mg compounds, which exhibit a perfect match for a dative covalent bond between them. Now, with the help of the "in situ" orbital correlation diagram, it becomes obvious that the metal-metal bond is a typical ionic bond, because when the Mg compound is brought close, the energy level of the HOMO of Al(I) compound decreases significantly, leading to a reversal of the HOMO-LUMO energy level order and the extension of the HOMO-LUMO band gap and subsequently minimal probability of any electron transfer. We expect that the novel concept of "in situ" orbital correlation will fundamentally enrich our understanding of chemical reactions, electron transfer pathways, and molecular bonding.
Entanglement generation is a cornerstone of quantum information science, yet its speed in Hermitian systems is fundamentally constrained by the coupling strength, a restriction known as the quantum speed limit. Here we demonstrate that this bound can be beaten by exploiting the unique topology of non-Hermitian systems near exceptional points (EPs). Using a pair of trapped ions, we engineer a parity-time symmetric Hamiltonian where the coalescence of eigenstates near the EP distorts the Hilbert space geometry, providing a shortcut for quantum state evolution. We observe that, as the system approaches the EP, the time required to generate a maximally entangled state is markedly reduced with respect to the limits imposed by the equivalent Hermitian interaction. We further uncover a fundamental physical trade-off whereby the acceleration of entanglement is intrinsically coupled to a reduction in the success probability, revealing the information cost of non-Hermitian speedup. Our results suggest that tailored dissipation, rather than being a source of decoherence, can serve as a powerful resource for accelerating quantum dynamics, offering a new paradigm for designing high-speed quantum gates and sensors in hardware-constrained platforms.
The evolution of soft robots into embodied intelligent systems relies fundamentally on precise proprioception. However, a universal solution for capturing continuous deformations during diverse interactions, particularly in spatially confined interventional scenarios, remains lacking. Here, we introduce a deep learning-enabled versatile shape perception method based on a single-ended multimode fiber (MMF). By leveraging the intrinsic integration advantages of optics, our minimalist reflective architecture physically eliminates the dependence on complex demodulation units and distal devices. Furthermore, treating chaotic optical speckle fields as data streams encoding high-dimensional shape information, reconfigurable neural decoders resolve a single physical channel into versatile perception modes tailored to heterogeneous tasks: discrete state confirmation on soft grippers (>99% accuracy), continuous shape tracking on bionic dexterous hands (~5-fold spatial resolution enhancement), and intuitive 3D morphological reconstruction of soft surgical robots (IoU>0.93). Overall, our work establishes a versatile framework for breaking hardware adaptability limits via computation, laying a solid foundation for closed-loop control in digital twins of soft robots.
Here we studied the aqueous transport of different alkali-metal ions in charged boron nitride nanotubes (BNNTs) and compared the results with those obtained in carbon nanotubes, using macroscopic, vertically aligned nanotube membranes at densities up to 107 pores cm-2. Our study reveals that ion transport in 3- and 12-nm-diameter charged BNNTs is fundamentally different from that in either carbon nanotubes of a similar size, or two-dimensional boron nitride nanochannels. We find two unexpected transport phenomena: ultrafast, cation-selective diffusion that exceeds Fickian diffusion up to 31-fold; and preferentially enhanced transport rates for Li+ over other alkali-metal ions (K+ and Na+) that are opposite to the ordering of their mobilities in bulk solution. We show that the overall fast transport of cations is due to diffusio-osmotic surface transport, while the preferentially enhanced transport of Li+ is believed to result from ion-specific interactions with the charged BNNTs. As a result of enhanced and cation-selective transport, the BNNT membranes produced per-pore osmotic-power densities up to 15,300 W m-2 in a 1 mM:1 M LiCl concentration gradient at pH 11. The energy-conversion efficiency approached the theoretical limit of 50% at pH 5.5. As a demonstration, we power a calculator, watch and light-emitting diode using 1-cm2 BNNT membranes in a salinity gradient. The unusual transport phenomena in BNNTs, as well as the flexible and scalable membrane-fabrication process, may enable ion-selective nanotube membranes optimized for lithium recovery, 'blue' osmotic energy and other separation and energy-conversion processes.
Soft magnetic actuators have gained significant interest for applications in minimally invasive medical robots, artificial muscles, soft robotic manipulators, and wearable bioelectronic interfaces, yet their functionality remains fundamentally limited by current magnetization strategies. To this end, a novel in-process printing and magnetization strategy with spatial and dynamic control of an external magnetic field during printing is developed to fabricate magnetorheological elastomers with fully customizable three-dimensional (3D) magnetization profiles. This method allows localized magnetic domain alignment in arbitrarily programmed orientations within a solid, enabling anisotropic actuation at micron to millimeter scales. The proposed method is highly sensitive to curing kinetics, material viscosity, and magnet positioning, which are characterized theoretically, experimentally, and in simulation. Structures magnetized in this way offer robust strain-sensing, information-encoding, and bio-inspired heterogeneous actuation capabilities. Demonstrations highlight this versatility, including a dragonfly with oppositely magnetized wings for tunable resonant actuation, an octopus-inspired swimmer whose magnetized legs reproduce aquatic locomotion, and a serpentine catheter with high degrees of freedom across 6 magnetic nodes. Together, these advances establish a versatile platform for designing magnetically responsive systems that couple programmable anisotropic actuation with biological complexity.
The clinical prognosis for osteosarcoma (OS) remains bottlenecked by chemoresistance and pulmonary metastasis. OS features dense infiltration by tumor‑associated macrophages (TAMs) that are hijacked into an immunosuppressive, pro-tumorigenic M2-like phenotype. Overcoming this therapeutic plateau requires a paradigm shift toward active remodeling of the tumor immune microenvironment. This review evaluates the trajectory of TAM-targeted interventions in OS, emphasizing the critical transition from monotypic phagocytosis checkpoint blockade (e.g., CD47, GD2) to multimodal synergistic regimens. We systematically dissect how next-generation nanomedicine, targeted metabolic stressors (ferroptosis, cuproptosis), and pharmacological rewiring can forcibly induce immunogenic cell death and reverse M2 polarization. Addressing the unique reconstructive demands of OS, we spotlight the development of immuno-regenerative scaffolds-bifunctional biomaterials engineered to synchronize post-resection tumor clearance with active osteogenesis. Finally, we highlight how spatial transcriptomics and biomimetic platforms are mapping physical immune-exclusion barriers and novel therapeutic subpopulations. Breaking the OS therapeutic stalemate ultimately demands interventions that breach these spatial architectures and fundamentally reprogram TAMs, guided by real-time functional imaging (e.g., ferumoxytol MRI) and high-resolution biomarkers (e.g., PSME2).
Seed vigor underpins uniform crop establishment, but its dynamic genetics are understudied. Combining high-resolution temporal phenotyping and genomics in upland cotton, we used the SeedRanger platform to record 17 image-based traits every 30 min over 120 h, revealing stage-specific heritability and identifying 541 seed-vigor loci. These loci show extensive pleiotropy and temporal coordination, forming a genetic network that preserves developmental continuity; 8.9% overlap regions under domestication selection, indicating concurrent optimization with fiber yield. Functional validation of FLA2, a candidate gene underlying a dynamic QTL, implicates auxin-mediated control of radicle elongation and cotyledon development. This temporal framework exposes dynamic genetic architecture and breeding targets for high-vigor crops.
This study provides a comparative kinematic analysis of futsal instep shot performance between trained athletes and novice players, addressing limited evidence on how multijoint kinematic patterns are associated with ball velocity. Twenty trained futsal athletes and twenty novice players performed standardized instep shots recorded using high-speed cameras at 240 fps. Research procedures included camera calibration, frame-by-frame motion analysis, reliability testing, and kinematic extraction using Dartfish software. Joint angles, angular velocities, torso orientation, and ball velocity were examined using independent-sample t-tests, effect sizes, and multiple regression analysis. Trained athletes exhibited more optimized multijoint kinematic patterns, characterized by more mechanically efficient knee positioning during foot placement and backswing, improved torso stability, and effective upper-limb positioning. Significant between-group differences were detected across most kinematic variables (p < 0.05). Knee angular velocity emerged as the strongest predictor of ball velocity (R² = 0.62, p < 0.01). Optimized lower- and upper-body kinematic patterns are associated with shooting proficiency and performance, supporting targeted technical training focused on optimizing shooting mechanics and kinematic efficiency.
Exciton dissociation in semiconducting nanostructures is crucial for optoelectronic applications, especially when free-carrier generation is required. Despite considerable research, the question of whether and how such generation occurs in strongly excitonic systems remains elusive. Here, we use one-dimensional precision graphene nanoribbons (GNRs) as a model system to investigate exciton dissociation. We systematically explore the interplay between ribbon length (l), excitation energy, and band dispersion in various precision GNRs. Ultrafast Terahertz conductivity measurements reveal that hot exciton dissociation dominates carrier generation, with ribbon length significantly influencing free carrier lifetimes. We identify a critical Bjerrum length (RB) of approximately 20 nm that determines whether photoexcited hot carriers in GNRs can dissociate before forming tightly bound excitons. For shorter ribbons (l < 2RB), rapid ~ps exciton formation prevails. Furthermore, the charge-carrier band dispersion in GNRs plays a critical role in determining dissociation efficiency. Long GNRs with strongly dispersed bands, and consequently low effective carrier masses, exhibit higher mobilities that promote efficient hot-exciton dissociation. These results advance fundamental understanding of dimensionality, energetics, and electronic structure in excitonic materials, providing design principles for optoelectronic devices based on excitonic materials.
Despite required simulation training and Fundamentals of Endoscopic Surgery certification, concerns remain about endoscopic competency among graduating general surgery residents. No prior study has directly evaluated resident endoscopic performance in clinical practice. Using the Society for Improving Medical Professional Learning (SIMPL) database, this study assesses general surgery resident competency and autonomy in colonoscopy, upper endoscopy, and sigmoidoscopy/proctoscopy. A retrospective analysis of the SIMPL database was conducted for general surgery residents completing endoscopic procedures between January 2015 and August 2025. Faculty-rated performance was dichotomized as competent (practice-ready/exceptional) versus not competent (unprepared/inexperienced/intermediate performance) and resident autonomy was dichotomized as meaningful (passive help/supervision only) versus not meaningful (show and tell/active help). Descriptive statistics on performance and autonomy were evaluated, including agreement between resident and faculty evaluations. Logistic regression was used to assess resident performance and autonomy according to training year, with case complexity as a covariate. A total of 3,325 cases were evaluated, consisting of 2,696 colonoscopies, 364 upper endoscopies, and 265 sigmoidoscopies/proctoscopies. Faculty observed competent performance in 35.3% of colonoscopies, 50.0% of upper endoscopies, and 42.3% of sigmoidoscopies/proctoscopies. Faculty observed meaningful autonomy in 60.7% of colonoscopies, 68.9% of upper endoscopies, and 59.2% of sigmoidoscopies/proctoscopies. The likelihoods of achieving competency and meaningful autonomy in the most complex colonoscopies were 23.6% and 40.8%, respectively. At the chief resident level, faculty observed competency in 70.6% of colonoscopies, 89.5% of upper endoscopies, and 87.3% of sigmoidoscopies/proctoscopies. Nearly one-third of colonoscopies performed by chief residents did not meet practice-ready competency standards, representing the most concerning finding of this study. Performance was even lower for complex cases, with fewer than one-quarter achieving competency and less than half demonstrating meaningful autonomy. Together, these findings highlight gaps in current training pathways and underscore the need to strengthen endoscopy education.
Lung-resident B cells are increasingly recognized as key contributors to protective immunity against respiratory viruses, yet the mechanisms that govern their generation and specialization remain poorly understood. Here, we identify B cell-intrinsic αv integrin as a critical negative regulator of germinal center (GC) dynamics and memory B cell formation in the lung following influenza A virus infection. Using B cell-specific αv knockout mice, we show that loss of B cell αv integrin leads to persistent GC activity within the inducible bronchus-associated lymphoid tissue and expansion of lung-resident memory B cells, including IgA+ and cross-reactive B cells capable of recognizing heterologous influenza variants. Single-cell transcriptomic and B cell receptor sequence analyses reveal that αv restricts clonal expansion and antigenic diversification of GC and memory B cells in the lung, but not in draining lymph nodes, indicating a spatially restricted mechanism of mucosal B cell regulation. These findings position αv integrin as a key checkpoint that constrains local mucosal B cell evolution and suggest previously unexplored strategies to improve mucosal vaccine efficacy by enhancing GC activity directly in the lung.
Variation is a fundamental principle of natural and artificial selection. Annual cycles in daylength or photoperiod are an environmental cue that most species in the plant and animal kingdoms use to determine the time of year and the direction of annual changes. Despite phylogenetic variation in mechanisms of light detection, the neural and molecular substrates that transduce photoperiod information are common across vertebrates. However, there is considerable conditional plasticity in the neuroendocrine mechanism that govern seasonal physiology leading to a spectrum of phenotypes within a single species. Here, we cover the phylogenetic history and conditional plasticity that contribute to photoperiodic polyphenisms. This Review presents the current understanding of how light is detected and represented in the vertebrate central nervous system and highlights phenotypic variation in photoperiod responses in amniotes. The Review provides future directions for addressing gaps in understanding how photoperiodic polyphenisms are involved in adaptations to changing environments.
Mechanical stress is the most important factor affecting the progression of osteoarthritis (OA), but the mechanism linking mechanical stress to transcriptional repression remains elusive. Here, the study finds that mechanical stress induced epigenetic changes that can serve as therapeutic targets for osteoarthritis. By using Piezo1 conditional knockout (Col2a1CreERT; Piezo1flox/flox) mice, it was found that Piezo1 activation by excessive mechanical stress can trigger chromatin remodeling via cytoskeletal force transmission, promoting the histone demethylase Kdm5c-mediated epigenetic silencing. Kdm5c in turn erases H3K4me3 marks from promoters of cartilage-anabolic genes Col2a1 and Runx3, silencing their expression. Genetic ablation of Kdm5c rescues mechanical stress-induced cartilage degradation. Through drug repurposing, the study identifies telmisartan as a direct Kdm5c inhibitor that blocks this pathway and demonstrates disease-modifying efficacy in mouse OA models and human cartilage explants. These results establish the Piezo1-Kdm5c axis as a fundamental driver of OA and position telmisartan as a mechano-epigenetic therapy with immediate translational potential.
Dark matter particles with sufficiently large interactions with ordinary matter can scatter in the Earth's atmosphere and crust before reaching an underground detector. This Earth-shielding effect can induce a directional dependence in the dark matter flux, leading to a sidereal daily modulation in the signal rate. We perform a search for such a modulation using data from the SENSEI experiment, targeting MeV-scale dark matter. We achieve nearly an order-of-magnitude improvement in sensitivity over previous direct-detection bounds for dark-matter masses below ∼1  MeV, assuming the standard halo model with a Maxwell-Boltzmann velocity distribution, and restrict the amplitude of a general daily modulation signal to be below 6.8  e/g/d.
The sequence-specific recognition of double-stranded DNA by biocompatible molecules is fundamental to molecular medicine and synthetic biology. Triplex-forming oligonucleotides (TFOs) enable programmable major groove recognition via Hoogsteen base pairing; however, the limited repertoire of natural nucleobases imposes strict constraints on target sequences and parallel motif triplexes require acidic conditions for stability. Here, we have expanded the triplex recognition space using nucleobases from an artificially expanded genetic information system (AEGIS). Through a systematic evaluation of 120 base triad combinations, we identify at least 12 modular triads that can be combined interchangeably to target duplex DNA containing standard, damaged, or synthetic base pairs with nanomolar affinity at neutral pH. We further demonstrate the versatility of this expanded recognition code by detecting oxidative lesions or AEGIS base pairs in enzymatically assembled duplex constructs using both chemically and enzymatically synthesized TFOs. This generalized framework provides a robust platform for precision gene-targeting, molecular sensing, and nucleic acid nanotechnology.