An In-Situ-Tag-Generation Proximity Labeling Technology for Recording Cellular Interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Interception Proximity Labeling for Interrogating Cell Efflux Microenvironment.

The difficulty in elucidating the microenvironment of extracellular H2O2 efflux has led to the lack of a critical extracellular link in studies of the mechanisms of redox signaling pathways. Herein, we mounted horseradish peroxidase (HRP) to glycans expressed globally on the living cell surface and constructed an interception proximity labeling (IPL) platform for H2O2 efflux. The release of endogenous H2O2 is used as a "physiological switch" for HRP to enable proximity labeling. Using this platform, we visualize the oxidative stress state of tumor cells under the condition of nutrient withdrawal, as well as that of macrophages exposed to nonparticulate stimuli. Furthermore, in combination with a proteomics technique, we identify candidate proteins at the invasion interface between fungal mimics (zymosan) and macrophages by interception labeling of locally accumulated H2O2 and confirm that Toll-like receptor 2 binds zymosan in a glycan-dependent manner. The IPL platform has great potential to elucidate the mechanisms underlying biological processes involving redox pathways.

Cell-Selective Multifunctional Surface Covalent Reconfiguration Using Aptamer-Enabled Proximity Catalytic Labeling.

Cell surface engineering provides access to custom-made cell interfaces with desirable properties and functions. However, cell-selective covalent labeling methods that can simultaneously install multiple molecules with different functions are scarce. Herein, we report an aptamer-enabled proximity catalytic covalent labeling platform for multifunctional surface reconfiguration of target cells in mixed cell populations. By conjugating peroxidase with cell-selective aptamers, the probes formed can selectively bind target cells and catalyze target-cell-localized covalent labeling in situ. The universal applicability of the platform to different phenol-modified functional molecules allows us to perform a variety of manipulations on target cells, including labeling, tracking, assembly regulation, and surface remodeling. In particular, the platform has the ability of multiplexed covalent labeling, which can be used to install two mutually orthogonal click reactive molecules simultaneously on the surface of target cells. We thus achieve "multitasking" in complex multicellular systems: programming and tracking specific cell-cell interactions. We further extend the functional molecules to carbohydrates and perform ultrafast neoglycosylation on target living cells. These newly introduced sugars on the cell membrane can be recognized and remodeled by a glycan-modifying enzyme, thus providing a method package for cell-selective engineering of the glycocalyx.

Giant oscillatory Gilbert damping in superconductor/ferromagnet/superconductor junctions.

Interfaces between materials with differently ordered phases present unique opportunities for exotic physical properties, especially the interplay between ferromagnetism and superconductivity in the ferromagnet/superconductor heterostructures. The investigation of zero- and π-junctions has been of particular interest for both fundamental physical science and emerging technologies. Here, we report the experimental observation of giant oscillatory Gilbert damping in the superconducting niobium/nickel-iron/niobium junctions with respect to the nickel-iron thickness. This observation suggests an unconventional spin pumping and relaxation via zero-energy Andreev bound states that exist not only in the niobium/nickel-iron/niobium π-junctions but also in the niobium/nickel-iron/niobium zero-junctions. Our findings could be important for further exploring the exotic physical properties of ferromagnet/superconductor heterostructures and potential applications of ferromagnet π-junctions in quantum computing, such as half-quantum flux qubits.

Evidence for anisotropic spin-triplet Andreev reflection at the 2D van der Waals ferromagnet/superconductor interface.

Fundamental symmetry breaking and relativistic spin-orbit coupling give rise to fascinating phenomena in quantum materials. Of particular interest are the interfaces between ferromagnets and common s-wave superconductors, where the emergent spin-orbit fields support elusive spin-triplet superconductivity, crucial for superconducting spintronics and topologically-protected Majorana bound states. Here, we report the observation of large magnetoresistances at the interface between a quasi-two-dimensional van der Waals ferromagnet Fe0.29TaS2 and a conventional s-wave superconductor NbN, which provides the possible experimental evidence for the spin-triplet Andreev reflection and induced spin-triplet superconductivity at ferromagnet/superconductor interface arising from Rashba spin-orbit coupling. The temperature, voltage, and interfacial barrier dependences of the magnetoresistance further support the induced spin-triplet superconductivity and spin-triplet Andreev reflection. This discovery, together with the impressive advances in two-dimensional van der Waals ferromagnets, opens an important opportunity to design and probe superconducting interfaces with exotic properties.

An inorganic prodrug, tellurium nanowires with enhanced ROS generation and GSH depletion for selective cancer therapy.

Organic prodrugs have been widely reported to avoid side effects and have been applied for precise tumor therapy in recent years. However, inorganic nano-prodrugs with localized generation of toxic products in the tumor have not been reported. Herein, we report an inorganic nano-prodrug, tellurium nanowires (TeNWs), that generate toxic TeO6 6- triggered by hydrogen peroxide (H2O2) for highly selective cancer chemotherapy. Bovine serum albumin and dextran conjugate coated TeNWs, with a length of ∼82 nm and a width of ∼7 nm, showed high stability in physiological medium. The interaction between TeNWs and intracellular H2O2 produces toxic TeO6 6- molecules greatly enhanced ROS generation, and the reaction product, verified as TeO6 6-, would react with glutathione (GSH) and thus decrease intracellular GSH levels, which greatly increases ROS levels in the tumor. Importantly, TeNWs selectively kill cancer cells by caspase-independent autophagic death and apoptosis, as well as exerting an immune response, while not affecting normal cells due to the high H2O2 levels in cancer cells. Moreover, after the sequential reaction with H2O2 and GSH, TeNWs were dissociated into small molecules and could be rapidly and completely removed from the body. Both in vitro and in vivo experiments indicate that TeNWs are a promising inorganic nano-prodrug that exerts good selective therapeutic effects on tumors.

Observation of Interfacial Antiferromagnetic Coupling between Magnetic Topological Insulator and Antiferromagnetic Insulator.

Inducing magnetic orders in a topological insulator (TI) to break its time reversal symmetry has been predicted to reveal many exotic topological quantum phenomena. The manipulation of magnetic orders in a TI layer can play a key role in harnessing these quantum phenomena toward technological applications. Here we fabricated a thin magnetic TI film on an antiferromagnetic (AFM) insulator Cr2O3 layer and found that the magnetic moments of the magnetic TI layer and the surface spins of the Cr2O3 layers favor interfacial AFM coupling. Field cooling studies show a crossover from negative to positive exchange bias clarifying the competition between the interfacial AFM coupling energy and the Zeeman energy in the AFM insulator layer. The interfacial exchange coupling also enhances the Curie temperature of the magnetic TI layer. The unique interfacial AFM alignment in magnetic TI on AFM insulator heterostructures opens a new route toward manipulating the interplay between topological states and magnetic orders in spin-engineered heterostructures, facilitating the exploration of proof-of-concept TI-based spintronic and electronic devices with multifunctionality and low power consumption.

Dirac surface state-modulated spin dynamics in a ferrimagnetic insulator at room temperature.

This work demonstrates markedly modified spin dynamics of magnetic insulator (MI) by the spin momentum-locked Dirac surface states of the adjacent topological insulator (TI), which can be harnessed for spintronic applications. As the Bi concentration x is systematically tuned in 5-nm-thick (Bi x Sb1-x )2Te3 TI films, the weight of the surface relative to bulk states peaks at x = 0.32 when the chemical potential approaches the Dirac point. At this concentration, the Gilbert damping constant of the precessing magnetization in 10-nm-thick Y3Fe5O12 MI films in the MI/TI heterostructures is enhanced by an order of magnitude, the largest among all concentrations. In addition, the MI acquires additional strong magnetic anisotropy that favors the in-plane orientation with similar Bi concentration dependence. These extraordinary effects of the Dirac surface states distinguish TI from other materials such as heavy metals in modulating spin dynamics of the neighboring magnetic layer.

Experimental signatures of spin superfluid ground state in canted antiferromagnet Cr2O3 via nonlocal spin transport.

Spin superfluid is a novel emerging quantum matter arising from the Bose-Einstein condensate (BEC) of spin-1 bosons. We demonstrate the spin superfluid ground state in canted antiferromagnetic Cr2O3 thin film at low temperatures via nonlocal spin transport. A large enhancement of the nonlocal spin signal is observed below ~20 K, and it saturates from ~5 down to 2 K. We show that the spins can propagate over very long distances (~20 µm) in such spin superfluid ground state and that the nonlocal spin signal decreases very slowly as the spacing increases with an inverse relationship, which is consistent with theoretical prediction. Furthermore, spin superfluidity has been investigated in the canted antiferromagnetic phase of the (11[Formula: see text]0)-oriented Cr2O3 film, where the magnetic field dependence of the associated critical temperature follows a 2/3 power law near the critical point. The experimental demonstration of the spin superfluid ground state in canted antiferromagnet will be extremely important for the fundamental physics on the BEC of spin-1 bosons and paves the way for future spin supercurrent devices, such as spin-Josephson junctions.

Role of Oxygen in Ionic Liquid Gating on Two-Dimensional Cr2Ge2Te6: A Non-oxide Material.

Ionic liquid gating can markedly modulate a material's carrier density so as to induce metallization, superconductivity, and quantum phase transitions. One of the main issues is whether the mechanism of ionic liquid gating is an electrostatic field effect or an electrochemical effect, especially for oxide materials. Recent observation of the suppression of the ionic liquid gate-induced metallization in the presence of oxygen for oxide materials suggests the electrochemical effect. However, in more general scenarios, the role of oxygen in the ionic liquid gating effect is still unclear. Here, we perform ionic liquid gating experiments on a non-oxide material: two-dimensional ferromagnetic Cr2Ge2Te6. Our results demonstrate that despite the large increase of the gate leakage current in the presence of oxygen, the oxygen does not affect the ionic liquid gating effect on  the channel resistance of Cr2Ge2Te6 devices (<5% difference), which suggests the electrostatic field effect as the mechanism on non-oxide materials. Moreover, our results show that ionic liquid gating is more effective on the modulation of the channel resistances compared to the back gating across the 300 nm thick SiO2.