Ferroptosis, an iron-dependent non-apoptotic cell death mode, has emerged as a promising strategy for tumor therapy, yet the direct delivery of iron-based nanomedicines will inevitably trigger marked anaphylactic reactions in normal tissues. Non-ferrous nanomedicines have thus attracted ever-increasing attentions, while their rational designs, functional exploitations and therapeutic mechanism clarifications remain great challenges. Herein, we report a palladium-tungsten oxide/carbon (Pd-WO2.90/C, PWC) nanomedicine via a green, facile and high-efficiency fabrication strategy. In response to the tumor microenvironment (TME, such as mild acidity, overexpressed peroxide (H2O2) and glutathione (GSH)), PWC exhibits intrinsic catalase (CAT)-like activity and triggers the generation of multiple reactive oxygen species (ROS) including hydroxyl radical (•OH), singlet oxygen (1O2) and carbon free radical (•C). More importantly, PWC achieves ferroptosis-like tumor regression with enhanced specificity and meanwhile efficiently induces immunogenic cell death (ICD) in tumor cells without inducing iron-related adverse reactions in normal tissues. Mechanistically, PWC depletes intracellular GSH to inactivate glutathione peroxidase 4 (GPX4), promotes lipid peroxidation (LPO) accumulation, and simultaneously triggers multi-Radical burst to amplify oxidative stress, collectively driving ferroptosis-like cell death. Furthermore, the PWC-induced ICD elicits robust anti-tumor immune responses, which further suppresses tumor growth and metastasis. In vitro and in vivo experiments consistently validate the superior anti-tumor efficacy and excellent biocompatibility of PWC, and the in-depth exploration of its therapeutic mechanism. This work not only develops a non-ferrous nanomedicine for efficient ferroptosis-like therapy and ICD induction, but also offers a versatile design paradigm for the development of next-generation non-ferrous nanomedicines.
Hexagonal MnTe is a prototypical semiconducting altermagnet whose properties are heavily influenced by intrinsic disorder, yet how the resulting diverse transport regimes shape its magnetotransport behavior remains to be clarified alongside the role of relativistic spin-orbit coupling (SOC). Here, we present a systematic study of the anisotropic magnetoresistance (AMR), planar Hall effect (PHE), and nonlinear transport in MnTe bulk single crystals. Below the Néel temperature (TN 304 K), the emergence of high-order harmonics in AMR and PHE within the high-temperature metallic regime reveals the interplay of magnetic order, crystalline symmetry, and SOC. At relatively lower temperatures, the disappearance of higher-order symmetries coincides with a transport crossover into the hopping conduction regime, suggesting that carrier localization diminishes the transport sensitivity to the Fermi-surface topology. In addition, we detect distinct second-order nonlinear Hall signals, providing evidence for a macroscopic inversion-asymmetric response in altermagnetic MnTe. Extending the investigations into the localized regime provides key insights into the subtle role of disorder and SOC in macroscopic charge transport. Our work thus underscores the necessity of exploring magnetotransport across diverse conducting regimes to comprehensively understand altermagnetic properties.
On-policy distillation (OPD) has become a core technique in the post-training of large language models, yet its training dynamics remain poorly understood. This paper provides a systematic investigation of OPD dynamics and mechanisms. We first identify that two conditions govern whether OPD succeeds or fails: (i) the student and teacher should share compatible thinking patterns; and (ii) even with consistent thinking patterns and higher scores, the teacher must offer genuinely new capabilities beyond what the student has seen during training. We validate these findings through weak-to-strong reverse distillation, showing that same-family 1.5B and 7B teachers are distributionally indistinguishable from the student's perspective. Probing into the token-level mechanism, we show that successful OPD is characterized by progressive alignment on high-probability tokens at student-visited states, a small shared token set that concentrates most of the probability mass (97
T cell receptor (TCR)-T cell therapy is effective for solid tumors, yet identifying potent, specific TCRs for tumor antigens is challenging. Conventional affinity maturation may cause fatal off-target toxicity. Catch bonds play a crucial role in mechanosensory receptor signaling, including the TCR, but their formation and potential to mitigate the challenges of TCR-T remain unclear. Here, we demonstrate that histidine scanning can identify TCR hotspots capable of forming additional catch bonds, which can be randomized to create TCR libraries for screening low-affinity, higher-potency variants. Mechanistically, histidine facilitates the formation of hydrogen bonds and salt bridges and fortifies the intracellular signaling cascade. Using this approach, we engineered different TCRs specific for various antigens, without off-target toxicity or on-target toxicity. Our findings introduce a universal method of engineering low-affinity, high-potency TCRs for safe TCR-T cell therapy, without requiring the structure for designing TCR libraries. Additionally, histidine scanning can be broadly applied to other mechanosensory ligand-recep tor systems.
Self-generated spin-orbit torque (SOT) in magnetic materials has emerged as a promising pathway for efficient magnetization control without external spin current sources. Here, we unveil an alternative mechanism for deterministic SOT polarity control based on inversion symmetry engineering via ferromagnet (Co) thickness gradients in [Co/Pt](p) multilayers with the repeating periods p. Unlike conventional approaches relying on spin Hall effect asymmetry in heavy metals, we modulate the spatial profile of spin current absorption and reflection across the stack, creating a net damping-like SOT driven by gradient-induced imbalanced spin accumulation. By inverting the Co gradient, we achieved polarity-reversed perpendicular magnetization switching, demonstrating that the SOT originates from structural symmetry breaking within the ferromagnetic layers. Second harmonic measurements confirm robust SOT switching efficiencies up to 294 Oe cm(2) MA(-1), along with enhanced thermal stability and scalability beyond bilayer systems. Our findings establish the symmetry-governed design principle for spin transport, enabling tunable and thickness-robust spintronic devices.
