Browse Articles

Selective <i>Para</i> ‐Functionalization of Aromatic C(sp ² )─H Bonds via Atomically Dispersed Photocatalysis

ABSTRACT Direct functionalization of aromatic C─H bonds is crucial in organic synthesis due to their wide applications in pharmaceutical chemistry and materials engineering, yet precise site selectivity remains challenging. Traditional methods often rely on electrophilic aromatic substitution or transition metal catalysis with directing group strategies, which can result in product mixtures or require pre‐installed functional groups. In this respect, recent advances using single‐atom catalysts (SACs) are promising due to their enhanced reactivity and selectivity. This study introduces a robust catalytic system for undirected para ‐C─H functionalization of electron‐rich arenes by using an atomically dispersed copper‐based photocatalyst. The method bypasses the requirement of pre‐installed directing groups, achieving site‐selective functionalization through an η 2 interaction with arenes under mild conditions, with a broad substrate scope, and excellent catalyst recyclability. Furthermore, this approach offers a novel method for incorporating functional groups into complex drug molecules, which is crucial in the synthesis of pharmaceuticals and natural products.

Aerodynamic barriers to inhaled furosemide delivery during dyspnoea revealed by experimental and computational modelling

Abstract Inhaled furosemide shows potential for relieving refractory dyspnoea, yet clinical trials have yielded inconsistent results. We hypothesise this failure stems from a “Dyspnoea Paradox”, where high inspiratory flows create an aerodynamic barrier. We evaluated furosemide delivery using a vibrating mesh nebuliser under simulated dyspnoeic conditions (tidal volume 1.39 L, frequency 28.6 min⁻¹). The study integrated standard Pharmacopoeial characterisation, in vitro deposition in a realistic human airway replica, and computational modelling (Large Eddy Simulation and Multiple-Path Particle Dosimetry). While standard tests indicated optimal aerodynamic properties (MMAD 3.03 μm), realistic modelling revealed a critical barrier. Both experimental and computational results showed excessive deposition in the upper parts of the airways, caused by a “Laryngeal Jet” that increases inertial impaction and turbulent dispersion. Standard Pharmacopoeial methods thus yield false-positive predictions of delivery efficiency for dyspnoeic patients. We propose a mechanistic hypothesis that rapid inhalation associated with air hunger filters out a significant portion of the therapeutic dose before it reaches the target tracheobronchial receptors, which may partially explain the inconsistent clinical outcomes. Clinical strategies must therefore shift from dose escalation to flow-governed delivery or shape-optimised carriers to overcome this aerodynamic filtration.

Programmable Chimeric Antigen Receptor T Cell Circuits With DNA Computing for Precision Tumor Therapy

ABSTRACT Chimeric antigen receptor (CAR) T cells, a promising cancer therapeutics, still face challenges in safety and efficacy due to the incapability to precisely regulate T cell activation. Here we develop a DNA‐logic CAR (DL‐CAR) system that enables programmable targeting and precise ablation of tumors with specific antigen combination patterns. The DL‐CAR system is engineered using HaloTag as an extracellular domain for DNA conjugation, which allows controlling the assembly of tumor‐targeting aptamers for universal and combinatorial antigen recognition via DNA logic computation. DL‐CAR‐T cells are shown to be capable of targeting tumor cells with different antigens and controlling the CAR circuit through AND, OR, and INHIBIT Boolean logic for specific T‐cell activation and cytolysis. The DL‐CAR system demonstrated high efficacy for tumor eradication in mouse models, with the AND‐, OR‐, and INHIBIT‐gated computation affording enhanced selectivity for tumors with specific antigen combinations. DL‐CAR may provide a new paradigm to develop programmable CAR‐T circuits for precision cancer therapy.

Genome-wide association mapping and haplotype analysis reveal the genetic architecture of sodicity tolerance in bread wheat (Triticum aestivum L.)

A spatially adaptive synthetic vegetation index for monitoring ecosystem changes in climatically heterogeneous basins

Abstract The vegetation in climatically heterogeneous regions exhibits significant spatial variability and temporal succession characteristics. It is crucial to obtain consistent vegetation characteristics in this region over time. Traditional single indices such as NDVI (Normalized Difference Vegetation Index), LAI (Leaf Area Index), and NPP (Net Primary Productivity) each have their own advantages, but they often show inconsistent trends when applied to complex vegetation. To effectively capture spatial heterogeneity and enhance the ecological interpretability, we propose a Dynamic Spatially Variable Weighted Synthesis Vegetation Index (DWS-SVI). Based on four Global Land Surface Satellite Dataset (GLASS) vegetation parameters (FVC (Fractional Vegetation Cover), LAI, NDVI, and NPP) and land cover types, this method employs the CRITIC method to perform dynamic weighting and generate continuous weight surfaces, ultimately synthesizing a comprehensive vegetation index at the pixel level. It combines “global trend and local adaptation” by integrating spatial heterogeneity modeling and multi-variable dynamic weighting, thereby overcoming the limitations of traditional methods in terms of spatial heterogeneity and ecological interpretability. Results show that over the past two decades, more than 69.4% of the area in the YRB has witnessed a significant improvement in vegetation conditions. The improvement was most notable in the summer, and it was mainly attributed to the improvement in the temperature and humidity conditions in this region. Compared with a single indicator, the DWS-SVI index can reflect the coordinated evolution of ecosystem structure and function, and can effectively suppress the observation errors caused by the bias of a single vegetation index, especially the “false greening” signals in transition zones and arid areas. Furthermore, the dominant factor map constructed based on DWS-SVI further reveals the differentiated driving mechanisms of ecosystems such as farmland, grassland, and forest, demonstrating that it has superior interpretability. This study provides a transferable framework for constructing spatially adaptive vegetation indices, enabling more reliable monitoring of ecosystem changes in large river basins and other climatically heterogeneous regions.

Discovery of Perilloxazole Pseudo‐Natural Products Yields a New Sterol Biosynthesis Inhibitor Chemotype

ABSTRACT Pseudo‐natural products (PNPs) are new arrangements of natural product (NP) fragments, creating chemical spaces that extend beyond those explored by nature and are unattainable via known biosynthetic pathways. Herein, we establish the design principles for agrochemically‐active PNPs based on characteristic pesticide features. We systematically applied this strategy to discover PNP agricultural fungicides, opening up a broad new avenue for developing novel NP‐derived pesticides. We designed perilloxazole PNPs by integrating cyclohexene and isoxazoline fragments. Cheminformatics analysis demonstrates that perilloxazole PNPs combine the advantageous properties of NPs and pesticides. Biological evaluation reveals that perilloxazole represents a new chemotype of sterol biosynthesis inhibitor with low toxicity to non‐target organisms, providing a foundation for the discovery of superior green fungicides. Perilloxazole PNPs exhibit notable control efficacy against major crop diseases that cause severe agricultural losses, holding broad application prospects and high market potential.

Cross-modal attentive fusion network for tri-modal lesion growth prediction

Topological Engineering From Non‐Emissive Chiral Metallomacrocycle to Interlocked Architecture for Strong Circularly Polarized Luminescence

ABSTRACT Interlocked architectures are crucial for stabilizing specific conformations to achieve superior performance. Herein, we proposes a vacant π‐site recombination strategy to achieve significant luminescence enhancement through topological engineering from non‐emissive chiral metallomacrocycles ( R / S ‐Au 4 ) to highly circularly polarized luminescence (CPL) catenanes ( R / S ‐Au 8 ). The dynamical structural transformation of metallomacrocycles ( R / S ‐Au 4 ) to catenanes ( R / S ‐Au 8 ) was monitored by 1 H and 31 P NMR spectroscopy. Excited state dynamics and theoretical studies revealed that the increase of heavy atom effect in catenanes ( R / S ‐Au 8 ) effectively increases spin‐orbit coupling constant from 4.03 ( R ‐Au 4 ) to 48.22 cm −1 ( R ‐Au 8 ), facilitating the intersystem crossing between S 1 and T 1 . While R / S ‐Au 4 with flexible metallocyclic structures tend to rapidly relax the excited states through thermally vibrational processes, interlocked structures of R / S ‐Au 8 lead to better rigidity, thus effectively suppressing non‐radiative deactivation and facilitating radiative T 1 →S 0 relaxation, thus achieving highly efficient CPL with ca. 39% quantum yield in solution. Solution‐processed circularly polarized organic light‐emitting diodes (CP‐OLEDs) based on R / S ‐Au 8 attain high‐efficiency deep‐red circularly polarized electroluminescence (CPEL) peaked at 685 nm, with external quantum efficiency (EQE) of 9.9% and electroluminescence asymmetric factor of ± 2.2 × 10 −3 . In any case, this upgrading approach from discrete macrocycles to interlocked architectures opens a new avenue for developing high‐performance emitting materials and devices.

Impedance study of the charge leakage phenomenon in ITO-free graphene-super-yellow light-emitting diode

Abstract The construction of hybrid organic-inorganic systems is usually aimed at increasing the electrical conductivity and modifying the work function of transparent and conductive electrodes. Here, we describe the fabrication and photoelectrical studies of a light-emitting diode incorporating graphene/molybdenum oxide as an anode and poly(para-phenylene vinylene) copolymer as an organic emitting layer. We observed increased hole injection from the anode relative to electron injection from the cathode, as well as undesirable hole-electron recombination at the graphene-polymer interface responsible for a significant charge leakage. Modeling the multilayer structure of organic light emitting diodes using electrical equivalent circuits based on the results of impedance spectroscopy measurements, we analyzed the electronic processes in the graphene/metal-oxide/organic layer junction. We developed a complex mathematical model to analyze and interpret impedance data. The original method that we present here provides a way to monitor the charge density of the main charge carriers as well as the leaked ones. The work paves the way towards understanding the interface charge transport phenomena in multilayer systems, in particular polymer light-emitting diodes.

Realization of fermionic Laughlin state on a quantum processor

Abstract Strongly correlated topological phases of matter are central to modern condensed matter physics and quantum information technology but often challenging to probe and control in material systems. The experimental difficulty of accessing these phases has motivated the use of engineered quantum platforms for simulation and manipulation of exotic topological states. Among these, the Laughlin state stands as a cornerstone for topological matter, embodying fractionalization, anyonic excitations, and incompressibility. Although its bosonic analogs have been realized on programmable quantum simulators, a genuine fermionic Laughlin state has yet to be demonstrated on a quantum processor. Here, we realize the ν  = 1/3 fermionic Laughlin state on IonQ’s trapped-ion quantum computer using an efficient and scalable Hamiltonian variational ansatz with 369 two-qubit gates on a 16-qubit circuit. Employing symmetry-verification error mitigation, we extract key observables that characterize the Laughlin state, including correlation hole, bulk-edge correspondence, and topological entanglement entropy, with strong agreement to exact diagonalization benchmarks. This work demonstrates an end-to-end workflow to simulate material-intrinsic topological orders and provides a starting point to explore its dynamics and excitations on digital quantum processors.

Multiple‐Bonding and Lability: Study of an Anionic Vanadium Alumanyl

ABSTRACT An anionic vanadium alumanyl complex is prepared by a reaction of neutral vanadocene and an alumanyl anion. Single‐crystal XRD revealed a significantly contracted V–Al bond relative to that of the neutral congener. Theoretical calculations using IBO and QTAIM analysis attributed this contraction to enhanced multiple‐bonding character based on the d‐p π‐backdonation from V to Al. Magnetic data confirms the S  = 1/2 spin state of this anion, with EPR spectroscopy displaying relatively strong coupling between the V‐centered unpaired electron and the 27 Al nucleus. Furthermore, V K ‐edge XANES and XPS data revealed the oxidation states of the V and Al centers, highlighting the reduced nature of both metal centers. Reactivity studies revealed the dissociation of the anionic alumanyl ligand from the V center even in the presence of the multiple V─Al bond character, in stark contrast to the reactivity of the neutral analogue, as supported by a DFT‐based mechanistic study.

Adaptive multi-robot formation control using distributed audio-visual sensing and bluetooth communication networks

Abstract This paper introduces a new method for distributed multi-robot formation control, in which the emphasis is placed on combining audio-visual inter-agent sensing with Bluetooth communication. We recommend a hierarchical control, which would include a local formation controller and centralized control for ESP32-based robots. The scheme is based on a two thread architecture with audio processing and display during video playback without sacrificing synchronous motor output. To dynamically change robot positioning, we’ve developed an adaptive formation system that uses acoustic signatures and visual landmarks obtained in situ. In a time-division multiple access protocol developed for low-latency between robots, communication is carried out by Bluetooth. Experiments have shown that with a line, wedge, and circle, and keeping the shape to within ±15 cm rms error is possible. When control loop frequencies are maintained above 50 Hz, the device achieves audio packet delivery rates of 92% percent. The distributed sensing reduces individual robot energy costs by approximately 34% compared to traditional architectures, measured at 8.2 W versus 12.5 W per robot for the centralized baseline. The system successfully tolerates temporary sensor occlusions of up to 2 seconds through dead-reckoning supported by acoustic observations; extended occlusions are acknowledged as a limitation that accumulates dead-reckoning drift. Field experiments show that the robot swarms of 3 to 12 units are able to be deployed safely, and that the platform can withstand communication disruptions, short-term sensor occlusions, and dynamic challenges.

Gene dependency-informed inference of response to targeted cancer therapies

Bioinspired Molecular Engineering of IRE1‐Gated DNAzymes for Self‐Adaptive Bidirectional Modulation of ER Stress

ABSTRACT Precise regulation of endoplasmic reticulum (ER) stress signaling in cancer remains a central challenge for nucleic acid–based therapeutics, largely due to their inability to discriminate ER‐stressed malignant cells and non‐stressed normal cells. Here we report an ER stress–responsive regulatory platform that couples the disease‐associated endoribonuclease activity of inositol‐requiring enzyme 1 (IRE1) to the conditional activation of DNA‐based effectors. By rationally grafting an X‐box binding protein 1 ( XBP1 )‐mimetic stem–loop “gate” onto canonical DNAzymes (IR‐Dz), we generate constructs that remain catalytically inert under basal IRE1 activity but are activated upon ER stress–induced IRE1 cleavage. The resulting IR‐Dz mediates cell‐selective c‐MYC silencing in ER‐stressed cancer cells, thereby attenuating ER stress while sparing normal counterparts. Redirecting IR‐Dz to IRE1 mRNA achieves the opposite outcome—self‐silencing of IRE1 and amplification of ER stress in tumor cells. This modular architecture can be adapted to other nucleic‐acid modalities, such as antisense oligonucleotides. By establishing IRE1 as an endogenous molecular trigger for spatially and contextually precise activation of nucleic acid effectors, our study introduces a general strategy for programmable, condition‐dependent gene regulation and dynamic modulation of ER stress signaling in cancer.

Knowledge-graph-guided diffusion for culturally authentic modernization and animation of heritage patterns

System-level integration of halide perovskite optoelectronics for its commercial deployment

Hydrogen Isotope Exchange in Pyridine Catalyzed by an Iron(II) Imido Complex: Counterion‐Directed Regioselectivity

ABSTRACT High‐spin ( S = 2) iron(II) imido complexes [Ph 2 B( t BuIm) 2 Fe═NDipp]M (M = Li + , K + , K(18‐c‐6) + ) are catalysts for the hydrogen isotope exchange (HIE) reaction with pyridine as the substrate. As dictated by the counter‐cation, these complexes catalyze site‐selective α ‐, α , β , γ ‐, and β , γ ‐deuteration of pyridine. Experimental and computational mechanistic investigations reveal the critical role of the counter‐cation in catalysis, which activates the substrate, facilitates deuteration, and dictates HIE regioselectivity. The stoichiometric reaction of pyridine with [Ph 2 B( t BuIm) 2 Fe═NDipp]Li affords the catalytically active bis(2‐pyridyl) complex [Ph 2 B( t BuIm) 2 Fe(2‐Py) 2 Li(THF) 2 ]. By maintaining coordination to the substrate during the catalytic cycle, Li + preorganizes pyridine for regioselective α ‐deuteration by this catalyst. On the other hand, [Ph 2 B( t BuIm) 2 Fe═NDipp]K reacts with pyridine to afford the 2‐pyridyl amido complex [Ph 2 B( t BuIm) 2 Fe(2‐Py)NHDipp] − , which has been structurally characterized with [K(18‐c‐6)(THF) 2 ] + and [K(dibenzo‐18‐c‐6)(THF) 2 ] + counterions. As dictated by the size of the counter‐cation, [Ph 2 B( t BuIm) 2 Fe═NDipp] − catalyzes regioselective α , β , γ ‐ and β , γ ‐deuteration of pyridine. Here, the counter‐cation stabilizes the appropriate pyridyl regioisomer for the selectivity‐determining deuteration step.

The cost-effectiveness of inventory reserves for preventing drug shortages in Germany: a health-economic evaluation

Abstract Based on a recent legislative change in Germany, maintaining a six-month inventory reserve for pharmaceuticals has become the primary strategy used by the German government to prevent shortages and stockouts. This study aimed to estimate the number of drug shortages preventable under the medicines stockpiling mandate and to determine the maximum stockpiling duration that remains cost-effective. The study adopted the perspective of the German social health insurance and analyzed a publicly available database containing information on all past drug shortages in Germany from the first entry in 2012 to May 2023 (n = 2768). The proportion of preventable drug shortages was estimated as a function of inventory duration. Additionally, secondary data were used to ascertain the costs associated with inventory carrying (including storage, capital, and expiration costs) and the gain in quality-adjusted life years (QALYs) resulting from avoiding relevant shortages of medication packages. Maintaining a six-month inventory could prevent approximately 70% of drug shortages. The empirical analysis revealed a diminishing incremental benefit of extending the drug supply duration, leading to an increasing marginal cost-per-QALY ratio. Based on a health opportunity cost–based cost-effectiveness threshold, the cost-effective upper limit of inventory duration under the current assumptions was approximately 922 days. This estimate was particularly sensitive to assumptions about FIFO (“first in, first out”) warehouse procedures, number of drug shortages, and the valuation of health gains. This study indicates that Germany’s recently introduced six-month inventory mandate could substantially reduce drug shortages and deliver good value for money, with a very high probability of cost-effectiveness across the willingness-to-pay thresholds examined in the sensitivity analysis. However, key uncertainties—especially around FIFO procedure compliance, health opportunity costs, and the clinical consequences of shortages—warrant ongoing monitoring and periodic reassessment as new evidence becomes available.

From “synthetic” to defined microbial communities for clearer terminology

Reactant‑Transporting Metal‐Support Interaction for Lattice Carbonate‑to‑Methane Catalysis

ABSTRACT As a core concept of heterogeneous catalysis, metal‐support interactions are pivotal controlling activity, selectivity, and stability via electronic and geometric effects. Here, we report a reactant‑transporting form of metal support interaction (MSI), named as strong metal‐reactive support interaction (SMRSI) where Pt/H 2 directly hydrogenates lattice carbonate in calcite to CH 4 with ≤ 415 °C onset and ∼98% selectivity (390–510°C). Because lattice carbon in carbonate minerals constitutes Earth's largest carbon reservoir, enabling low‑temperature lattice–carbonate conversion offers a catalytic lever to accelerate the slow carbon cycle (ACC) complementary to fast carbon cycle (FCC)‑based CO 2 management. Operando techniques show a permeable amorphous interphase that dynamically encapsulates Pt, transports CO 3 2− to active sites, and crystallizes into Ca(OH) 2 , thereby sustaining a mobile triple‑phase boundary, where carbonate‑derived *CO intermediate was hydrogenated to CH 4 . It is resolved that a low‑temperature interfacial CO 2 release is diagnostic of boundary decomposition. Kinetics separate a CO 3 2− ‑diffusion‑limited solid‑state path at low temperatures from a high‑temperature route akin to gaseous‑CO 2 hydrogenation. The hydrogenated solid is re‐carbonated by CO 2 , regenerating CaCO 3 and retaining selectivity over cycles. Conceptually, the SMRSI extends MSI from electronic/geometric tuning to reactant transport, illustrating how moving solid‐solid@gas interfaces mediate transformations of solid reactants.