Browse Articles

Structural basis underlying the autoinhibition of the formin FHOD1 and its phosphorylation-dependent activation

Chemiluminescence‐Powered Immunotherapy for Deep Tumors: Promoting PD‐L1 Degradation and Igniting Pyroptosis Through Subcellular Trafficking and Targeting

ABSTRACT Organelle‐targeted therapy represents a promising strategy for cancer therapy and immune activation. Here, we present a novel Chemiluminescence‐Powered Immunotherapy (CPIT) platform designed to induce immunogenic pyroptosis and promote PD‐L1 degradation by exploiting two key subcellular organelles—lysosomes and the endoplasmic reticulum (ER). CPIT utilizes a PD‐L1‐targeted delivery vehicle (up to 10.8 %ID/g) to facilitate PD‐L1 degradation within lysosomes (>55% efficiency) and concurrently delivers a dual‐locked chemiluminescence‐resonance energy transfer (CRET) system to the ER for localized pyroptosis. The dual‐locking mechanism ensures tumor‐selective and ER‐confined activation, maximizing oxidative damage and specifically inducing pyroptosis while minimizing off‐target toxicity. In vivo studies demonstrate remarkable tumor selectivity (due to tumor‐specific delivery plus tumor‐selective activation), robust regression of metastatic tumors, and the induction of a durable adaptive immune response. CPIT overcomes the limitation of conventional photodynamic therapy‐driven immunogenic cell death (ICD) strategies, being effective only for superficial tumors. Simultaneously, it lowers the immune activation threshold by promoting PD‐L1 degradation, addressing the challenge of T cell exhaustion common in ICD‐based cancer immunotherapies. This approach holds promise as a transformative approach to treating hard‐to‐reach malignancies and expanding the reach of immunotherapeutic strategies. The modular design of CPIT enables rapid substitution of protein‐specific ligands or alternative chemiluminescent donors, further expanding its potential for diverse cancer immunotherapy applications.

Proximity‐Driven Non‐Volatile Spin and Valley Control in a Van Der Waals Antiferromagnetic Heterostructure

ABSTRACT The integration of non‐volatile spin and valley control in 2D quantum systems remains a pivotal challenge for spintronic and valleytronic functionalities. Here, we demonstrate persistent spin and valley polarizations in a van der Waals heterostructure comprising bulk antiferromagnetic CrPS 4 and monolayer MoSe 2 , achieved via interfacial magnetic proximity effects. The 1L‐MoSe 2 /bulk‐CrPS 4 heterostructure exhibits non‐volatile hysteresis in chiral photoluminescence (PL), directly linked to the antiferromagnetic ordering of bulk‐CrPS 4 . This helicity of PL persists at zero field, enabled by the spin‐polarized charge transfer from the K valley in the MoSe 2 monolayer to the conduction band of CrPS 4 , breaking the valley degeneracy without external stimuli. Remarkably, the PL helicity switches surprisingly at a magnetic field of ∼ 0.5 T, a 17‐fold smaller than the spin‐flip field of ∼8.5 T in bulk CrPS 4 . Our work establishes bulk antiferromagnet‐based heterostructure as a robust platform for low‐energy, magnetically tunable quantum devices, bridging the gap between the transient valleytronic phenomena and practical non‐volatile applications.

Oligomerization is required for channel formation of MctB and for copper resistance of Mycobacterium tuberculosis

Recent Progress on Flexible Multimodal Sensors: Decoupling Strategies, Fabrication and Applications

ABSTRACT Flexible multimodal sensors have garnered significant attention in research areas such as electronic skin, advanced robotics, and personalized health monitoring due to their ability to leverage the complementary advantages of diverse sensing units, thereby a primary decoupling strategy exploits differences in the fundamental types of signals generated. Nevertheless, flexible multimodal sensors persistently face challenges like signal crosstalk and complex integration processes, which constrain their performance. This review delineates recent advances in flexible multimodal sensor decoupling through fundamental material design guided by physical principles, structural design, and AI‐driven signal decoupling architectures. Additionally, we explore the various applications of flexible multimodal sensors, encompassing environmental monitoring, physiological health tracking, human‐machine interaction, and robotic perception. Finally, the conclusion, challenges, and future perspectives for next‐generation flexible multimodal sensing systems are discussed.

VarLand: A pipeline to map the structural landscape of missense variants at the proteome scale

Architected Interpenetrating Phase Microlattice With Superior Vibration Attenuation and Energy Absorption Performance

ABSTRACT With the increasing demand for material performance, traditional pure materials no longer meet the stringent requirements. Interpenetrating phase composites (IPCs), composed of two or more completely interconnected constituent phases, have garnered significant attention for their extraordinary capabilities. Here, we propose a novel fabrication method for interpenetrating phase microlattices (IPMs) synthesized with a resin skeleton and flexible rubber as the secondary phase. The stress–strain curves of different types of IPMs were obtained by static compression tests, which revealed highly enhanced toughness and specific energy absorption through the combination of size effect and lattice topology design. Noncontact dynamic response measurements were used to analyze the dynamic properties of both skeletons and IPMs. By leveraging the intrinsic energy dissipation capacity of the introduced secondary soft phase, IPMs exhibited a maximum 76.3% attenuation range and a maximum 31.5 dB transmissibility loss. The average transmissibility versus structural density was compared with that of similar IPC attenuation systems, demonstrating the superior energy dissipation performance of the IPMs.

Electrostatic Ion Trapping in Organic Electrochemical Transistors for Record Neuromorphic Memory Performance

ABSTRACT Organic electrochemical transistors (OECTs) leverage the chemical tunability of polymeric semiconductors; however, their potential as memory devices remains constrained by insufficient ion retention. Previous studies on physical trapping of ions within polymer crystalline domains have generally reported memory windows below 5.3 V. Here, we achieve molecular‐level hysteresis control by designing a dual‐functional zwitterionic crosslinker that creates an electrostatic ion‐trapping channel. Its fixed anionic sulfonate group establishes a repulsive barrier to delay ion injection, while its cationic ammonium site forms a deep electrostatic trap that creates a 2.03 eV barrier, thereby stabilizing the doped state, and collectively producing pronounced hysteresis. GIWAXS under sequential biasing reveals reversible lamellar dynamics, enabled by ionic interactions among side‐chain‐tethered zwitterion units. The resulting OECTs achieve record hysteresis strength (96.4 V) and memory window (8.65 V) while maintaining an on/off ratio ∼10 6 and 86.4% conductance retention after 200,000 pulses. Moreover, the Z‐FPA scheme generalizes to other polymer semiconductors, providing a polymer‐agnostic route to high‐fidelity neuromorphic OECTs. Synaptic metrics are more symmetric; device‐informed models reach 92.87% on MNIST, and ECG reservoir computing confirms biosignal compatibility. Our findings provide key molecular insights into the material design and operating mechanisms critical for advancing next‐generation neuromorphic OECTs.

IRF1 is a context-dependent homeostatic gatekeeper of basal immunity and antiviral readiness

Environmentally Stable N‐Type Conducting Polymer with High Intrinsic Stretchability

ABSTRACT The development of flexible electronics has driven an urgent demand for conducting polymers that combine exceptional electrical performance with mechanical adaptability. In the construction of complementary circuits, integrating p‐type and n‐type conducting polymers is critical, yet developing stretchable n‐type ones has long remained a challenge. We employ the refined regulation of polymer‐polymer interaction to enhance PBFDO's intrinsic stretchability (crack‐onset strain up to 100%) and environmental stability (5‐fold stability enhancement vs. pristine PBFDO), while achieving 2265 S/cm conductivity at 100% strain with stable recovery after 1000 cycles. Building on these advancements, we have successfully developed stretchable epidermal electrophysiological electrodes and organic thermoelectric devices—each conclusively validating the material's practical utility. The epidermal electrodes enable high signal‐to‐noise ratio recording of electrophysiological signals, while the thermoelectric devices operate stably under 60% bidirectional tensile strain. This work thus establishes new fundamental principles for engineering high‐performance stretchable n‐type conducting polymers, paving the way for next‐generation flexible electronics.

Metabolic Enzyme‐Inspired Molecular Clusters for Advanced Type 2 Diabetic Complications by Alleviating Immunosuppression

ABSTRACT Type 2 diabetes mellitus is the most prevalent disease in the world, with one‐tenth of the population suffering from the disease, and the most critical challenges are its complications that induce high disability and mortality rates. The state‐of‐the‐art therapeutic agents can manage glucose but fail to prevent renal failure as well as neurodegeneration with immunosuppression. Herein, we developed a deep learning design strategy that exploits the ‘size‐fitting effect’ to engineer an atomic‐precision metal cluster for preventing diabetic complications by targeting metabolic abnormality and immunosuppression. The designed AuZn cluster achieves almost 100% α‐amylase inhibition and 88% α‐glucosidase inhibition, resulting in the normalized glycated hemoglobin and sustained glucose control. The intrinsic redox properties reduce oxidative stress damage, promoting β‐cell regeneration and metabolic stress alleviation. Consequently, the renal function, the most prevalent complications, shows that glomerular filtration can be restored to normal levels without urinary protein, while the clinical dulaglutide is not show any improvement. The key marker during early neurocognitive disorders, the amyloid precursor protein (APP) induced by complications, can be effectively suppressed, and diabetes induced organelle degeneration in neurons can be restored.

Senescence Reprogramming Unleashes Tumor Immune Surveillance via Coordinated Gene Modulation

Abstract Cellular senescence can recruit immune cells for tumor therapy through the senescence‐associated secretory phenotype (SASP). However, its therapeutic efficacy is limited by immune tolerance and the immunosuppressive tumor microenvironment (TME). Reprogramming tumor‐specific senescence through coordinated modulation of P16 INK4a and PD‐L1 enhances tumor immunogenicity and alleviates immunosuppression. To achieve this, a target‐enhanced gene delivery nanoparticle is engineered using the urokinase plasminogen activator receptor (uPAR) as a senescence‐specific targeting ligand, combined with a telomerase reverse transcriptase (TERT) promoter and a nuclear localization signal‐microtubule‐associated sequence (NLS‐MTAS) peptide. This system efficiently induces tumor‐specific senescence through cell‐cycle arrest and promotes the chemotactic recruitment of cytotoxic immune cells. In vivo, the nanoparticle induces a robust anti‐tumor response without causing systemic toxicity and significantly enhances the therapeutic efficacy of αCTLA‐4 immune checkpoint blockade in subcutaneous, lung metastasis, postoperative recurrence, and spontaneous tumor models. This study emphasizes the therapeutic potential of reprogramming tumor‐specific senescence to improve targeted gene delivery and immunotherapy outcomes, offering a viable approach for the treatment of immunologically “cold” tumors.

A luminescent reporter assay to quantify SORL1 ectodomain shedding and retromer-dependent endosome recycling activity

Mesoscale Magnetostructural Phase Separation in Fe‐deficient Fe ₅ GeTe ₂

Abstract 2D Van der Waals ferromagnet Fe 5‐x GeTe 2 (F5GT) is promising for spintronic applications due to its high Curie temperature, layered structure, and ability to host complex magnetic textures. However, the origin of its sample‐dependent magnetic anisotropy remains unclear, hindering control of its magnetic behavior. Here, spatially resolved cryogenic scanning transmission electron microscopy (STEM) is used to correlatively map magnetism, lattice structure, and chemistry across atomic‐to‐micron scales. This is revealed that only mesoscale, not nanoscale, inclusions of a Fe‐deficient secondary phase significantly modify magnetic behavior, establishing a previously unrecognized critical length scale. This phase separation, induced by quenching, leads to in‐plane magnetic anisotropy, while slow cooling confines separation to a few nanometers and preserves out‐of‐plane anisotropy. These findings reconcile prior inconsistencies and establish a predictive framework for tuning magnetism in F5GT through thermal processing, with broader implications for controlling anisotropy in other 2D magnetic materials.

Gene expression analysis and proximity labeling reveal post-transcriptional functions of the yeast RNA polymerase II regulator Def1

High Performance 4.6 V LiCoO ₂ Cathode Materials Enabled by Surface Lattice Modulation

ABSTRACT Charging the cathode of LiCoO 2 (LCO) to higher voltages, typically 4.6 V, is able to increase reversible capacity, but meanwhile raises serious stability issues. Here, through a decomposition‐induced reconstruction (DIR) process, we demonstrate the possibility of modulating the surface lattice of LCO with high precision in depth control, thereby enabling the 4.6 V LCO cathode to have both high capacity and structural integrity. Following the precise construction of a conformal Y(OH)CO 3 nanoshell, a sintering process induces the hydrocarbonate decomposition, which releases CO 2 to transform the layered structure of the LCO crust into rock‐salt‐like lattices, forming a renovated surface with high electrochemical and mechanical stability. The prepared LCO cathode delivers a high reversible capacity of 215.8 mAh g −1 at 0.1 C with an extraordinary capacity retention of 93.0% after 100 cycles at 4.6 V. The much‐improved stability is meanwhile manifested by cyclability test at 1 C (85.5% vs 13.6% of pristine LCO after 500 cycles), as well as tests at harsh conditions. Our results highlight the essential role played by the surface chemistry in addressing the stability issue of high voltage LCO cathode, and provide useful guidelines for the development of lithium‐ion batteries with higher energy density.

Polarimetric Photodetector with Ultrahigh‐Sensitivity and Polarity Reverse Based on Quasi‐1D Semimetal (TaSe ₄ ) ₂ I/2D MoTe ₂ Heterojunction

Abstract Polarimetric photodetectors, capable of resolving both intensity and polarization states of light, are pivotal for advanced multispectral imaging and target recognition. Examples have been demonstrated for applications such as autonomous vehicle lidar systems and polarization‐based biomedical imaging, where accurate polarization information improves target detection and contrast. However, conventional polarimetric detectors are constrained by complicated optical components and single‐band polarization resolution. Here, a mixed‐dimensional heterojunction strategy is proposed that synergizes the unique optoelectronic properties and giant anisotropy of quasi‐1D Weyl semimetal with 2D semiconductor 2H‐MoTe 2 , achieving great dark current suppression and dual‐band polarization‐spectrum detection through interfacial band engineering. The (TaSe 4 ) 2 I/2H‐MoTe 2 photodetectors demonstrate high‐performance broadband operation (395–2200 nm) with a detectivity of 2.1×10 12 Jones, responsivity of 40 A W −1 , and quantum efficiency exceeding 11400%, setting a new benchmark for comprehensive performance in phototransistors. Notably, the intrinsic wavelength‐dependent dichroic inversion of (TaSe 4 ) 2 I enables the orthogonal polarization response polarity reversal between the visible (532 nm) and infrared (1550 nm) bands. Note that dual‐band polarization imaging is successfully achieved, which can be used for multispectral interference identification. This work demonstrates a feasible strategy by constructing mixed‐dimensional semimetal/semiconductor heterojunctions toward future ultrahigh‐sensitivity and broadband polarimetric detectors.

Ultrahigh Cell Density 3D Bioprinting by Acoustic Fluids‐mediated Stereolithography

Abstract Dense cell populations and their complex structures are the essentials of physiologically functional solid organs, but their biomimetic construction is challenging. Here, an ultrahigh cell density (UHCD) bioprinting system is presented for fabricating organ‐analogous intricate architectures based on an acoustic fluids‐mediated stereolithography (ASL) technique. The ASL can achieve cell aggregation on a prepolymerized solid–liquid interface with densities comparable to native tissues through focused surface acoustic waves‐induced vortices. Meanwhile, the ASL‐based UHCD bioprinting shows reduced light scattering in each ultrathin layer printing process, reaching cell densities of 1 billion cells mL −1 . Additionally, by incorporating an acoustic‐assisted medium exchange system, the ASL facilitates the bioprinting of multicellular components in arbitrary architectures. Based on these features, ASL's capability in fabricating structure‐mimetic liver tissue models with regenerative functionalities is demonstrated. It is believed that the ASL technique achieves breakthroughs in UHCD bioprinting, opening new avenues in the development of artificial tissue and organ engineering.

The divergent roles of tryptophans W354 and W217 in OCT1 transport: Similar localization, distinct functions

Flexible and Robust Metasurface‐Based Wearable Sensor for Intelligent Human Monitoring

ABSTRACT Wearable sensors enabling noninvasive healthcare monitoring encounter significant challenges in preserving signal integrity under motion artifacts and mechanical deformation. Here, we present for the first time a wearable sensor that integrates topologically protected flexible metasurface technology, combining topological photonics with AI‐enhanced sensing technology to enable multifunctional human monitoring. This intelligent system harnesses electromagnetic wave‐body interactions to precisely capture cardiopulmonary dynamics, effectively overcoming the limitations of conventional wearable sensors in dynamic conditions. Specifically, the topological design of the sensor ensures stable operational performance even in bent or fractured states, while deep learning algorithms facilitate robust extraction of personalized biometric features to simultaneously achieve multiple healthcare functions, including vital sign monitoring, activity recognition, and individual identification. Experimental results demonstrate the system's capability for real‐time health assessment across diverse scenarios, from exercise to rest states. By combining adaptive wearability with intelligent signal processing, this platform represents a transformative approach to next‐generation smart healthcare systems, advancing applications from chronic disease management to AI‐driven personalized healthcare.