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S‐Nitrosothiols as Thiol‐Protecting Groups for Controlled Thiol‐Maleimide Crosslinking of Homogeneous Soft Hydrogels
ABSTRACT The thiol‐maleimide Michael‐type addition is used in bioconjugation and hydrogel crosslinking for its chemoselectivity and rapid kinetics under physiological conditions. However, this same reactivity limits its use for soft hydrogels, as gelation often proceeds faster than precursor mixing, leading to spatially heterogeneous networks. Here, S‐nitrosothiols (RSNOs) are introduced as thiol‐protecting groups that suppress premature thiol‐maleimide coupling and enable homogeneous mixing of polymer precursors prior to on‐demand crosslinking. Despite common assumptions about RSNO instability, RSNO‐modified 4‐arm polyethylene glycol (PEGSNO) is stable in aqueous solution for months at 4°C protected from light. The nucleophiles sodium ascorbate or sodium thiosulfate (STS) trigger thiol regeneration and controlled crosslinking with maleimide‐modified PEG. The resulting hydrogels are homogeneous with Young's moduli tunable across a physiologically relevant range by independently varying nucleophile identity, concentration, or polymer content. In a cell‐adhesive system based on maleimide‐modified cold water fish skin gelatin, STS‐triggered gelation supports 3D cell encapsulation, with cytocompatibility depending on formulation and cell type, while matrix stiffness is tuned through polymer content and STS concentration. This work establishes RSNO chemistry as a previously unexplored strategy for controlled thiol‐maleimide crosslinking, enabling reproducible, homogeneous network formation, with potential for dual‐function materials coupling network formation with local reactive nitrogen species delivery.
Realization of Air‐Stable Two‐Dimensional Superconductor Nb <sub>2</sub> Pd <sub>3</sub> Te <sub>5</sub> With Quasi‐One‐Dimensional Pair Density Modulation
ABSTRACT Two‐dimensional (2D) superconductors provide a fertile platform for exploring reduced‐dimensional superconductivity and emergent quantum phenomena. Incorporating quasi‐one‐dimensional (quasi‐1D) structural motifs into 2D superconductors offers a powerful route to engineer strong electronic anisotropy, enabling unconventional superconducting states and anisotropic superconducting transport functionalities. However, such systems remain rarely realized. Here we report the realization of a 2D superconductor Nb 2 Pd 3 Te 5 , exhibiting an intrinsic quasi‐1D pair density modulation. Monolayer and bilayer Nb 2 Pd 3 Te 5 is synthesized via van‐der‐Waals epitaxy. Using ultralow‐temperature scanning tunneling microscopy/spectroscopy, we observe the quasi‐1D crystal structure and superconductivity below ∼0.6 K with a pronounced quasi‐1D pair density modulation. Remarkably, both monolayer and bilayer Nb 2 Pd 3 Te 5 show strong air stability. Our findings establish atomically 2D Nb 2 Pd 3 Te 5 as a robust and promising platform for exploring novel low‐dimensional quantum phenomena and anisotropy‐enabled superconducting devices.
Photothermal‐Photoelectric Synergistic Management in High‐Entropy Alloys for Full‐Spectrum Solar CO <sub>2</sub> ‐to‐CH <sub>4</sub> Conversion
ABSTRACT Current photothermocatalysts, characterized by inadequate photogenerated electrons for accelerating reaction kinetics as well as excessive demand for high light intensity, face major obstacles to practical application. In this study, a heteroarchitectured photothermocatalyst is presented by integrating the FeCoNiCuCr (FCNCuCr) high‐entropy alloys (HEAs) photothermal layer, the Al doped ZnO (AZO) photoelectric layer, and the thermal radiation blocking component of chromium‐plated glass (Cg). The obtained Cg/FCNCuCr/AZO photothermocatalyst exhibits an unprecedented CO 2 ‐to‐CH 4 conversion performance, with CH 4 yield reaching 5082.9 µmol g −1 h −1 , which is 14 and 4 times that obtained from pristine FCNCuCr HEAs and Cg/FCNCuCr, respectively, surpassing the state‐of‐the‐art photothermocatalysts and photocatalysts for gas‐solid atmospheric pressure CO 2 conversion with H 2 O supplied as proton source. Thanks to effective photothermal management, the Cg/FCNCuCr/AZO heteroarchitectured photothermocatalyst achieves full‐spectrum solar absorption by minimizing thermal radiation, thereby realizing excellent photothermal conversion capability. Meanwhile, the sputtered AZO photoelectric layer is integrated to establish an interfacial Schottky barrier, harnessing the photoelectric synergy, and further reducing the reaction barrier for CO 2 ‐to‐CH 4 conversion. The present photothermal‐photoelectric synergistic management strategy enlightens the design of high‐performance photothermocatalysts for solar driven CO 2 conversion.
Structure‐Engineered Nanoporous Vanadium Oxide Memristors for Reconfigurable Synapse–Neuron Integration and Synergistic Robotic Motion
ABSTRACT Neuromorphic sensory‐to‐motor interfaces require compact devices that can combine nonvolatile synaptic weight storage with volatile neuronal firing, yet these functions typically rely on distinct material and circuit mechanisms. Here, we report a structure‐engineered VO y /nanoporous VO x heterostructure that enables electrically selectable nonvolatile and volatile switching within a vanadium oxide memristor platform. Annealing‐induced interfacial diffusion and oxidation produce an asymmetric stack comprising a crystalline VO y layer that supports threshold insulator‐to‐metal transition dynamics and an oxygen‐vacancy‐rich nanoporous VO x region that promotes filamentary conductance modulation. In a 16 × 16 crossbar array, identically fabricated cells are reconfigured either as artificial synapses exhibiting multilevel retention and analog long‐term potentiation/depression or as artificial neurons producing relaxation‐oscillator spiking and diverse neuronal response features. By pairing two cells as a one‐synapse–one‐neuron unit, the programmed synaptic conductance modulates the neuronal firing frequency and measured current‐spike amplitude, thereby linking analog weight storage with spike‐based signal generation. Using measured device characteristics, a hardware‐informed spiking neural network recognizes rock–paper–scissors images with high accuracy, and its output commands are coupled to a memristive synergistic motor system that drives a robotic hand to generate counter‐gestures. These results suggest that structure‐engineered nanoporous vanadium oxide memristors can serve as reconfigurable building blocks for neuromorphic sensory‐to‐motor interfaces.
Synergistic Bidirectional Crystallization for High‐Performance Perovskite Solar Cells
ABSTRACT Traditional n‐i‐p perovskite solar cells (PSCs) have achieved remarkable power conversion efficiencies exceeding 26%, yet their performance and stability remain critically bottlenecked by interfacial voids and detrimental trap states at the buried interface. These structural anomalies fundamentally originate from the conventional top‐down crystallization process, where a rapidly formed top crust induces a solvent blockade effect, trapping residual solvents that subsequently evaporate to leave detrimental buried voids. Here, we overcome this kinetic limitation via a synergistic bidirectional crystallization strategy, enabled by a dual‐functional molecular linker, diethyl phosphoramidate (DAPE). By strongly anchoring to the SnO 2 substrate and chemically bridging perovskite precursors, DAPE induces a synchronous bottom‐up growth front that complements the anti‐solvent‐induced top‐down crystallization. This kinetically reconstructed process maintains open solvent‐evasion channels, effectively eliminating the solvent blockade to yield a dense, void‐free interface. Consequently, the optimized devices exhibit relaxed residual stress and minimized non‐radiative recombination, achieving a champion power conversion efficiency of 26.25% with superior operational stability. Our work underscores the vital role of regulating crystallization kinetics to eliminate physical interfacial anomalies, offering useful insights for the further development of efficient n‐i‐p PSCs.
Janus Nanozyme With Programmable Catalytic Switching for Adaptive Therapy of Diabetic Wounds
ABSTRACT Diabetic wound healing requires dynamic bidirectional regulation of reactive oxygen species (ROS). Herein, guided by density functional theory (DFT) calculations, we propose a programmable strategy to engineer catalytic pathways via an intimate heterointerface in Janus‐structured Cu‐Ag nanoparticles (CuAg‐J). Theoretical simulations reveal that the unique Cu‐Ag heterointerface induces a charge transfer to oxygen intermediates, enabling spontaneous formation of reactive species and pH‑switchable catalytic activity. Under acidic conditions, CuAg‐J exhibits peroxidase (POD)‐like activity ( K m = 0.19 mM, V max = 0.38 µM/s) for antibacterial ROS generation. Under neutral conditions, it displays superoxide dismutase (SOD)‐like and catalase (CAT)‐like activities ( K m = 9.48 mM, V max = 6.88 µM/s) for ROS scavenging and oxygen production. In an infected diabetic wound model, this bidirectional ROS regulation effectively breaks the oxidative stress–hypoxia–inflammation vicious cycle, significantly accelerating healing and achieving 92.04% wound closure by Day 14. This study not only presents a high‐performance nanozyme but also provides a new design rationale for engineering intelligent catalytic materials capable of autonomous function switching in response to dynamic microenvironmental conditions.
Triboelectric Tactile Sensors for Embodied Intelligence: Design, Performances, and Applications
ABSTRACT Embodied intelligence is driving artificial intelligence from digital reasoning toward real physical interaction, while tactile perception capabilities lag behind algorithmic advances and have become a critical bottleneck restricting the practical implementation of robotic closed‐loop interaction. We propose that triboelectric event‐driven tactile sensing can serve as a tactile information acquisition strategy for embodied intelligence. With its distinctive characteristics of mechanically triggered output and self‐powered operation, it provides a new route to overcoming the limitations of signal acquisition, transmission, and power supply in complex environments and under high‐density deployment. Based on this perspective, this review centers on triboelectric event‐driven tactile sensing and systematically discusses the implementation pathways of triboelectric tactile sensors for embodied intelligence from four aspects: the conversion mechanisms from tactile events to electrical signals, material and structural design, key deployment performance, and embodied interactive applications. Particular emphasis is placed on revealing the intrinsic relationships among design strategies, deployment capabilities, and scenario adaptability. Finally, this review further discusses the key challenges and future directions that must still be addressed for triboelectric event‐driven tactile sensing to advance from device‐level performance optimization toward an event‐driven system‐level perception paradigm.
Multiscale Ion Transport Optimization in High‐Mass‐Loading Cathodes for Aqueous Zinc‐Ion Batteries
ABSTRACT High‐mass‐loading cathodes are essential for translating aqueous zinc‐ion batteries (AZIBs) from laboratory demonstrations to practically relevant energy‐storage devices because they increase the fraction of electrochemically active materials and thereby improve device‐level energy density. However, increasing cathode loading and thickness simultaneously aggravates charge transport limitations, electrolyte infiltration insufficiency, and structural degradation, leading to severe polarization, poor active‐material utilization, and rapid performance decay. In this review, we present a multiscale framework for understanding and optimizing high‐mass‐loading AZIB cathodes, spanning the microscale, mesoscale, and macroscale. At the microscale, we discussed how doping, vacancy, and interlayer‐spacing modulation regulate electronic structure, Zn 2+ diffusion, and structural stability of active materials. At the mesoscale, we examine pore architecture, cathode components, and fabrication strategies, with emphasis on porosity, tortuosity, electrolyte accessibility, and integrated charge transport in thick cathodes. At the macroscale, we highlight the importance of electrode balancing and electrolyte management for translating material‐level advances into practical cell performance. We further outline emerging directions, including operando characterization, cross‐scale modeling, data‐driven materials discovery, and scalable manufacturing. By connecting material chemistry, electrode architecture, and device integration, this review provides a coherent roadmap for the rational design of high‐mass‐loading cathodes and the development of energy‐dense, commercially relevant AZIB systems.
Elastomeric 3D‐Printed Microenvironments Enable Nanonewton Force Measurements in Healthy and Diseased Human Pluripotent Stem Cell‐Derived Neuroepithelial Cells
ABSTRACT During neural development, cells generate and respond to mechanical forces within their microenvironment while they migrate and differentiate. These forces are central to the development of the human brain, as they are transduced into intracellular signals that regulate key neurobiological processes and may be involved in pathological processes. However, measurement of such forces in the nanonewton (nN) range within a three‐dimensional (3D) microenvironment remains technically challenging and computationally intensive. Here, we present a solution to this challenge, based on elastomeric 3D microstructures fabricated via two‐photon polymerization (2PP) and a tailored wet‐etching process. The resulting free‐standing beam architectures enable the quantification of nN forces exerted by pluripotent stem cell‐derived neuroepithelial progenitor cells. We characterized the morphology of the cells and the forces they exerted using live‐cell confocal imaging microscopy, scanning electron microscopy (SEM), supported by an in‐house routine for intensity‐based deflection measurements with sub‐pixel resolution, and atomic force microscopy (AFM). Using this platform, we precisely quantified neuronal traction forces down to 1.2 nN from both healthy neural cells and those carrying a TSC2 gene mutation linked to tuberous sclerosis complex (TSC). The proposed elastomeric microenvironment paves the way for investigating cytoskeletal mechanics, neuromechanobiology in 3D, and for developing in vitro disease treatment models.
Stress Transfer Within Microphase‐Separated Structures: A Post‐Synthetic Strategy to Impart Mechanoresponsiveness to Block Copolymer Materials
ABSTRACT Mechanoresponsive polymers, which exhibit changes in properties such as color in response to mechanical stimuli, have attracted increasing attention for smart materials. Among various design strategies, mechanophore‐incorporated systems are widely used approaches that enable precise molecular‐level design and control; however, this approach often suffers from complicated synthesis and limited applicability to existing materials such as block copolymers, which have found widespread industrial use as high‐performance materials. Here, we present a post‐synthetic strategy enabled by exploiting microphase‐separated structures to impart mechanochromism to existing polymer systems while retaining the advantages of mechanophore‐based approaches. By exploiting the microphase‐separated structure of styrene–butadiene–styrene (SBS) block copolymers, blending with polystyrene bearing a tetraarylsuccinonitrile (TASN) mechanophore enables domain‐selective localization of the mechanophore within the rigid domains without chemical modification of the host polymer. The resulting materials exhibit fluorescence upon tensile deformation originating from force‐induced TASN cleavage, demonstrating mechanoactivation even under minimal deformation of the hard domains. The mechanoresponse is governed by the molecular weight and content of the mechanophore‐containing polystyrene. Importantly, bulk mechanical properties are preserved and can even be enhanced. This strategy establishes a scalable platform for integrating mechanochemical functionality into existing polymer systems.
Entropy Modulation Boosted Ultra–Broadband Electromagnetic Wave Absorption of Si(Zr,Hf,Ta,Ti,Nb)BCN Ceramics
ABSTRACT SiMBCN ceramics containing one or multiple metallic elements are synthesized via chemical modification of polyborosilazane using one to five metal alkylamino compounds with an equimolar ratio (i.e., M = Zr, Hf, Ta, Ti, and/or Nb). The effects of the number and types of metallic elements on the local lattice distortion, microstructure, dielectric properties, and electromagnetic wave absorption (EMA) performance are systematically investigated via experiments and ab initio calculations. These results show that increasing the number of metallic elements remarkably increases the local lattice distortion and suppresses the crystallization of the ceramics, which strongly affects the dielectric properties, showing a significant entropy effect. Particularly, the SiZrHfTaTiNbBCN ceramics remain in nearly amorphous state even after annealing at 1600°C for 5 h. Under the synergistic effect of annealing temperature and entropy engineering, the SiZrHfNbBCN ceramic develops a unique microstructure consisting of a ZrHfNbCN/Si 3 N 4 /C free core with abundant interfaces and a low‐dielectric β‐Si 3 N 4 ‐based shell. This microstructure balances the impedance matching and dielectric loss, resulting in an ultra‐broad effective absorption bandwidth at 1.90 mm (7.65 GHz), which is superior to all previously reported polymer‐derived ceramics (PDCs) at thickness < 2 mm and therefore presents a significant advance in ceramic‐based EMA materials for high‐temperature applications.
Organic n‐Type Molecule Mediated Crystallization Regulation for Sn‐Pb Perovskite Solar Cells
ABSTRACT Narrow‐bandgap Sn‐Pb perovskites have showcased great potential for constructing tandem perovskite solar cells (PSCs). However, Sn 2 + in Sn‐Pb PSCs is readily oxidized to Sn 4 + , and such B‐site Sn 4 + will introduce excess positive charge and causes severe p‐type self‐doping, which pins the Fermi level and aggravates non‐radiative recombination. Additionally, the Sn‐based component crystallizes far more rapidly than that of Pb, resulting in unbalanced Sn‐Pb crystallization. To address these challenges, we develop a novel n‐type molecule NDBH as perovskite additive. This molecule offers three key advantages: prevents the oxidation of Sn 2 + through chelation and blocks oxygen ingress along grain boundaries; balances the crystallization rates of Sn‐Pb perovskite by selectively chelating Sn 2 + ; modifies the perovskite surface to be more n‐type. With this organic n‐type molecule, the inverted Sn‐Pb PSCs achieve power conversion efficiency (PCE) of 24.11%. The devices also exhibited remarkable long‐term stability, retaining over 90% of their initial efficiency after 600 h of maximum power point (MPP) tracking. This approach of designing multifunctional n‐type molecules offers a new perspective for enhancing the efficiency and stability of Sn‐Pb PSCs.
Data‐Driven Materials Science for Energy‐Sustainable Applications
ABSTRACT Materials science is underpinned by structure‐property relationships that govern the function of a material. These relationships can be encoded into algorithms and integrated into machine‐learning models that enable the prediction of materials and their cognate properties. However, machine‐learning models are largely being trained on computed data owing to a worldwide shortage of real‐world (experimental) datasets. This review describes how to capture and collate experimental data from scientific literature using artificial‐intelligence (AI) methods to produce materials‐domain‐specific datasets or language models. Their application in AI‐driven enquiries that facilitate progress in energy‐sustainable materials science is then illustrated via six case studies that cover: training machine‐learning models, data‐driven materials discovery, optimizing manufacturing processes, mapping phases of materials, forecasting materials‐centric research trends, and classifying types of materials using automated prompt engineering. The future of materials‐domain‐specific datasets, language models, and decision‐making workflows using AI agents is then envisioned for the energy sector. The intrinsic challenges of accessing historical dark data in materials science are then described and contrasted with timely opportunities for leveraging massive amounts of experimental data from laboratories in going forwards; by exploiting electronic‐lab notebooks, high‐throughput experiments, and digital‐twin technologies. These opportunities are illustrated for energy‐sustainable materials science, especially the photovoltaic and battery industries.
Lignin Mimicking Protein Methylation Augments the Efficacy of FOLFOX Chemotherapy by Anchoring Thymidylate Synthase
ABSTRACT FOLFOX has served as the standard chemotherapy regimen for advanced stages, specifically in the treatment of pancreatic, colorectal, and bladder cancers. However, the issues of excessive toxicity and prolonged treatment cycles persist. To address this limitation, we developed a novel methylated amino acid‐modified lignin inspired by biological methylation, creating a pH‐responsive charge‐reversal drug delivery system for FOLFOX chemotherapy. This system stabilizes thymidylate synthase (TS) and combines with deoxyuridine monophosphate (dUMP) to demonstrate significantly improved therapeutic outcomes of FOLFOX against colorectal cancer (CRC). The FOLFOX‐loaded nanodrug showed targeted antitumor activity against CRC and induced tumor cell death through multiple mechanisms, including apoptosis, necrosis, cell cycle regulation, DNA damage, and reactive oxygen species generation. Furthermore, the nano‐formulation activated immune responses to enhance chemotherapeutic potency and effectively reducing renal toxicity associated with chemotherapy drugs. These findings suggest that protein methylation‐mimicked lignin could be a valuable addition to current first‐line chemotherapy options and holds promise for enhancing chemotherapy against solid tumors.
Engineered Chiroplasmonic Nanointerfaces Enable High‐Dissymmetry Circularly Polarized Electrochemiluminescence From Achiral Luminophores
ABSTRACT Circularly polarized electrochemiluminescence (CP‐ECL) provides an emerging route to encode chiral information into electrochemically generated light, but current strategies largely rely on intrinsically chiral luminophores, limiting molecular diversity, device integration, and dissymmetry‐factor amplification. Here, a strategy based on engineered chiroplasmonic nanointerfaces is developed for high‐dissymmetry CP‐ECL from achiral luminophores. In this design, luminophores are spatially confined around helicoid Au nanocrystals within a nanoscale plasmonic environment, and the resulting hybrid nanocrystals are assembled into monolayer films to couple chiroplasmonic near fields with electrochemically generated excited states. Using Ru(bpy) 3 2+ as a model achiral ECL luminophore, the helicoid Au@SiO 2 ‐Ru nanocrystal monolayer electrode produces mirror‐image CP‐ECL responses with a high dissymmetry factor of |g CP‐ECL | ≈ 1.1. Control experiments and electromagnetic simulations reveal a synergistic mechanism in which chiroplasmonic near‐field induction predominantly breaks the emission symmetry, whereas circular‐polarization‐dependent extinction further amplifies the far‐field circular polarization contrast. Extension to another achiral ECL luminophore suggests that this strategy may be applicable beyond the Ru(bpy) 3 2+ system. By enabling circular polarization without requiring intrinsically chiral luminophores, this approach can be readily integrated with established achiral ECL chemistries and devices, offering opportunities for chiral sensing, electrochemiluminescent photonics, and optical information encoding.
Nuclear Pore Mechanotransduction in Oncology: A Structural Axis of Vulnerability for Targeted Intervention
ABSTRACT Nuclear pore complexes (NPCs) are massive protein assemblies that gate the nuclear envelope to regulate nucleocytoplasmic transport. Beyond their canonical role as conduits, NPCs act as mechanosensitive regulators that translate cytoskeletal, extracellular, and lamina‐derived forces into transport decisions coupled to cellular state. In malignancy, NPCs undergo extensive remodeling—marked by protein overexpression, hyperpermeability, and compromised scaffold integrity. While these alterations drive invasion and transcriptional plasticity, they simultaneously expose a lethal mechanical vulnerability; transformed cells become critically dependent on this altered NPC state. We propose the “nuclear mechanostat” as a testable conceptual framework in which NPC barrier stringency and nuclear mechanics are reciprocally coupled. Through the lenses of dilation, elastic deformation, and structural memory, we synthesize existing evidence and develop the hypothesis that pharmacological disruption of the permeability barrier or scaffold architecture erodes nuclear resilience. Because cancer cells operate near a mechanical failure threshold, targeting these conserved mechanotransducers reveals a pan‐cancer axis of vulnerability, opening new frontiers for precision oncology.
Ultrathin 2D Multivariate Hydrogen‐Bonded Organic Framework Nanosheets for Fluorescent DNA Sensing
ABSTRACT The multivariate strategy is generally incompatible with densely packed structures, as this approach typically requires porous frameworks to manage the steric demands of incorporated functional groups. Without sufficient free volume, the frameworks are prone to structural transformations driven by steric hindrance. Here, we demonstrate that this limitation can be overcome by exploiting an interaction hierarchy in hydrogen‐bonded organic frameworks (HOFs), where strong directional charge‐assisted hydrogen bonds define the framework while weaker interactions accommodate steric perturbations. This enables the extension of the multivariate strategy to densely packed systems, yielding multivariate HOFs with well‐defined structures and tailored functionalities. Specifically, a carboxylate‐amidinium‐based layered HOF (HOF‐FAFU‐4) was synthesized as a prototype platform. It enables the integration of diverse building blocks and precise tuning of the spatial arrangement of functional groups. Benefiting from their layered structure, these materials can be further exfoliated into ultrathin 2D nanosheets, thereby enhancing the accessibility of functional sites. These ultrathin 2D nanosheets serve as fluorescent sensing platforms for DNA detection, achieving a limit of detection (LOD) of 8.1 pM and demonstrating broad generality for multiple DNA analytes. This work not only broadens the scope of the multivariate strategy but also expands the structural diversity and applicability of HOFs.
Nonorthogonal Polarization‐Multiplexed and Detachable Diffractive Processors
ABSTRACT Polarization multiplexing provides an elegant route for parallel all‐optical processing, yet its intrinsic orthogonality fundamentally limits channel capacity and interlayer interaction in diffractive systems. We present a detachable diffractive processor that leverages nonorthogonal polarization multiplexing to overcome these bottlenecks. The processor features a convolutional‐like architecture composed of detachable diffractive layers, enabling global and interlayer function multiplexing with accelerated training and expanded versatility. Experimentally, we realize 12 independent functions—4 classifiers and 8 holograms—across 4 polarization‐decoupled channels in a dual‐layer system and extend to 18 channels supporting 6 classifiers and 36 holograms using a triple‐layer configuration. Furthermore, we demonstrate a multi‐level optical encryption framework that combines image transformation and holographic generation. This work establishes a scalable framework for multifunctional diffractive computing, enabling compact processors, high‐capacity holography, and secure optical information technologies.
Functional integrity of mesolimbic-hippocampal circuits is associated with anhedonia in individuals with early life stress
Anhedonia reflects a transdiagnostic deficit in a range of processes that impact reward and motivation. While human neuroimaging has mainly focused on striatal-related alterations in anhedonia, animal models suggest hippocampal [HPC] novelty processing regulates mesolimbic dopamine activity, implicating mesolimbic-HPC alterations in anhedonia. Childhood trauma, which disproportionately impacts HPC structure and function, may exacerbate this vulnerability. The present study of 37 males and 55 females examined whether HPC alterations interact with childhood trauma to predict anhedonia in humans. Using fMRI in a sample enriched for anhedonia, we assessed three HPC-related processes: resting-state connectivity with mesolimbic targets in the ventral tegmental area [VTA] and nucleus accumbens [NAc], task-based HPC novelty response, and task-based HPC modulation of VTA activation reflecting novelty-evoked facilitation of target detection. Significant interactions emerged for anticipatory anhedonia: reduced HPC-NAc connectivity, reduced novelty response, and weaker HPC→VTA modulation were each associated with greater anticipatory anhedonia among individuals with high childhood trauma. Moreover, LASSO regression confirmed these interactions as unique predictors. These findings suggest that early life adversity interacts with alterations in HPC-mesolimbic signaling to contribute to individual differences in anhedonia, highlighting the HPC as a potential target of motivation-related deficits in striatum. Significance Statement The ability to process rewarding stimuli and initiate goal-directed behavior is critical for human functioning. While human neuroimaging has highlighted the role of striatal function in these processes, animal evidence suggests that hippocampal modulation of mesolimbic dopamine signaling is critical for motivated behavior. The present study translates this framework to humans, demonstrating that hippocampal-mesolimbic functional integrity interacts with childhood trauma to predict individual differences in anticipatory anhedonia (i.e., impairments in one's ability to anticipate and pursue rewards). These findings implicate the hippocampus as a potential upstream contributor to motivational deficits and highlight early life stress as a key context in which mesolimbic circuit dysfunction becomes behaviorally relevant.
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.3
This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix I and Appendix II). Updates are published regularly and can be found on the ASCO Publications website .