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Effective cancer immunotherapy is usually blocked by immunosuppressive factors in the tumour microenvironment, resulting in tumour promotion, metastasis and recurrence. Here we combine lipid nanoparticle–mRNA formulations and dendritic cell therapy (named CATCH) to boost the cancer–immunity cycle via progressive steps to overcome the immunosuppressive tumour microenvironment. Multiple types of sugar-alcohol-derived lipid nanoparticles are conceived to modulate the cancer–immunity cycle. First, one type of lipid nanoparticle containing CD40 ligand mRNA induces robust immunogenic cell death in tumoural tissues, leading to the release of tumour-associated antigens and the expression of CD40 ligand. Next, dendritic cells engineered by another type of lipid nanoparticle encapsulating CD40 mRNA are adoptively transferred, which are then activated by the CD40 ligand molecules in tumoural tissues. This promotes the secretion of multiple cytokines and chemokines, and the upregulation of co-stimulatory molecules on dendritic cells, which are crucial for reprogramming the tumour microenvironment and priming the T-cell responses. After dendritic cells present tumour-associated antigens to T cells, all the above stepwise events contribute to boosting a potent tumour-specific T-cell immunity that eradicates established tumours, suppresses distal lesions and prevents tumour rechallenge.

Systems with flat bands are ideal for studying strongly correlated electronic states and related phenomena. Among them, kagome-structured metals such as CoSn have been recognized as promising candidates due to the proximity between the flat bands and the Fermi level. A key next step will be to realize epitaxial kagome thin films with flat bands to enable tuning of the flat bands across the Fermi level via electrostatic gating or strain. Here, we report the band structures of epitaxial CoSn thin films grown directly on the insulating substrates. Flat bands are observed by using synchrotron-based angle-resolved photoemission spectroscopy (ARPES). The band structure is consistent with density functional theory (DFT) calculations, and the transport properties are quantitatively explained by the band structure and semiclassical transport theory. Our work paves the way to realize flat band-induced phenomena through fine-tuning of flat bands in kagome materials.

Tumor-associated immune cells play a crucial role in cancer progression. Myeloid-derived suppressor cells (MDSCs), for example, are immature innate immune cells that infiltrate the tumor to exert immunosuppressive activity and protect cancer cells from the host's immune system and/or cancer-specific immunotherapies. While tumor-associated immune cells have emerged as a promising therapeutic target, efforts to counter immunosuppression within the tumor niche have been hampered by the lack of approaches that selectively target the immune cell compartment of the tumor, to effectively eliminate “tumor-protecting” immune cells and/or drive an “anti-tumor” phenotype. Here we report on a novel nanotechnology-based approach to target tumor-associated immune cells and promote “anti-tumor” responses in a murine model of breast cancer. Engineered extracellular vesicles (EVs) decorated with ICAM-1 ligands and loaded with miR-146a and Glut1, were biosynthesized (in vitroor in vivo) and administered to tumor-bearing mice once a week for up to 5 weeks. The impact of this treatment modality on the immune cell compartment and tumor progression was evaluated viaRT-qPCR, flow cytometry, and histology. Our results indicate that weekly administration of the engineered EVs (i.e., ICAM-1-decorated and loaded with miR-146a and Glut1) hampered tumor progression compared to ICAM-1-decorated EVs with no cargo. Flow cytometry analyses of the tumors indicated a shift in the phenotype of the immune cell population toward a more pro-inflammatory state, which appeared to have facilitated the infiltration of tumor-targeting T cells, and was associated with a reduction in tumor size and decreased metastatic burden. Altogether, our results indicate that ICAM-1-decorated EVs could be a powerful platform nanotechnology for the deployment of immune cell-targeting therapies to solid tumors.

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Understanding the dynamics of skyrmion nucleation and manipulation is important for applications in spintronic devices. In this contribution, the spin textures at magnetic domain-boundaries stimulated by application of in-plane magnetic fields in a centrosymmetric kagome ferromagnet, Fe3Sn2, with thickness gradient are investigated using Lorentz transmission electron microscopy. Switching of the in-plane magnetic field is shown to induce a reversible transformation from magnetic stripes to skyrmions, or vice versa, at the interface between differently oriented domains. Micromagnetic simulations combined with experiments reveal that the rotatable anisotropy and thickness dependence of the response to the external in-plane field are the critical factors for the skyrmion formation. In addition, it is shown that the helicity of skyrmions can also be controlled using this dynamic process. The results suggest that magnetic materials with rotatable anisotropy are potential skyrmionic systems and provides a different approach for nucleation and manipulation of skyrmions in spintronic devices.

Barium distannide (BaSn2), a potential precursor for stannene, is predicted to be a topological insulator. However, little is known about BaSn2as the material is extremely air-sensitive. Here we present, for the first time, characterization of BaSn2by scanning/transmission electron microscopy. We use advanced imaging and spectroscopy techniques to show disproportionation of BaSn2particles into β-Sn + BaxSny. X-ray diffraction analysis confirms that this disproportionation is driven by exposure to a low-pressure environment.

Topological magnetic textures such as skyrmions are being extensively studied for their potential application in spintronic devices. Recently, low-damping ferrimagnetic insulators (FMI) such as Tm3Fe5O12have attracted significant interest as potential candidates for hosting skyrmions. Here, we report the detection of the spin-Hall topological Hall effect (SH-THE) in Pt/Tm3Fe5O12and Pt/Y3Fe5O12bilayers grown on various orientations of Gd3Ga5O12substrates as well as on epitaxial buffer layers of Y3Sc2Al3O12, which separates the FMI from the substrate without sacrificing the crystal quality. The presence of SH-THE in all of the bilayers and trilayers provides evidence that rare-earth ions in either the FMI or substrate may not be critical for inducing an interfacial Dzyaloshinskii–Moriya interaction that is necessary to stabilize magnetic textures. Additionally, the use of substrates with various crystal orientations alters the magnetic anisotropy, which shifts the temperatures and strength of the SH-THE.

Transition metal complexes capable of photoinduced spin crossover have been widely investigated because of their potential to enable ultrafast optical control of information processing. However, any real application of photoswitchable molecules requires that spin crossover be paired with additional functionality such as long-range magnetic order. Important advances combining these functions are notably reported for a number of bimetallic Prussian Blue analogues; however, to date, PBA-based magnetic photoswitches can only operate below 150 K due to loss of magnetic order. In contrast, cobalt ferrite is a ferrimagnetic semiconductor with a Curie temperature of 790 K and extremely favorable magnetic properties by comparison to state-of-the-art PBAs. The mixed valence electronic structure of cobalt ferrite is reminiscent of cobalt–iron PBA, which is a well-known photoswitch. To investigate the potential for photoswitching in this material, we employ transient XUV spectroscopy to probe charge and spin dynamics with element-specific resolution on the femtosecond time scale. Results show that 400 nm light excites a metal-to-metal charge transfer transition, which drives the crossover of high-spin Co2+to low-spin Co3+with a time constant of 405 ± 29 fs and an internal quantum efficiency of unity. This result establishes the existence of efficient photoswitching in a new class of robust ferrimagnetic spinel ferrites.

Sepsis, a condition caused by severe infections, affects more than 30 million people worldwide every year and remains the leading cause of death in hospitals1,2. Moreover, antimicrobial resistance has become an additional challenge in the treatment of sepsis3, and thus, alternative therapeutic approaches are urgently needed2,3. Here, we show that adoptive transfer of macrophages containing antimicrobial peptides linked to cathepsin B in the lysosomes (MACs) can be applied for the treatment of multidrug-resistant bacteria-induced sepsis in mice with immunosuppression. The MACs are constructed by transfection of vitamin C lipid nanoparticles that deliver antimicrobial peptide and cathepsin B (AMP-CatB) mRNA. The vitamin C lipid nanoparticles allow the specific accumulation of AMP-CatB in macrophage lysosomes, which is the key location for bactericidal activities. Our results demonstrate that adoptive MAC transfer leads to the elimination of multidrug-resistant bacteria, including Staphylococcus aureusand Escherichia coli, leading to the complete recovery of immunocompromised septic mice. Our work provides an alternative strategy for overcoming multidrug-resistant bacteria-induced sepsis and opens up possibilities for the development of nanoparticle-enabled cell therapy for infectious diseases.

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In this age of global warming, the automotive industry is seeking to minimize the energy required to manufacture and operate its products without sacrificing performance and safety or increasing cost. Toward this end, whether cars and trucks are powered by internal-combustion engines or batteries, lowering vehicle weight is a major contributor to reducing energy consumption by increasing fuel efficiency. “The industry is driven by fuel efficiency,” said David Matlock of the Colorado School of Mines, who has helped develop advanced high-strength steels (AHSSs) used in autos.

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Alternations of collagen and mineral at the molecular level may have a significant impact on the strength and toughness of bone. In this study, scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS) were employed to study structural and compositional changes in bone pathology at nanometer spatial resolution. Tail tendon and femoral bone of osteogenesis imperfecta murine(oim, brittle bone disease) and wild type (WT) mice were compared to reveal defects in the architecture and chemistry of the collagen and collagen-mineral composite in the oimtissue at the molecular level. There were marked differences in the substructure and organization of the collagen fibrils in the oimtail tendon; some regions have clear fibril banding and organization, while in other regions fibrils are disorganized. Malformed collagen fibrils were loosely packed, often bent and devoid of banding pattern. In bone, differences were detected in the chemical composition of mineral in oimand WT. While mineral present in WT and oimbone exhibited the major characteristics of apatite, examination in EELS of the fine structure of the carbon K ionization edge revealed a significant variation in the presence of carbonate in different regions of bone. Variations have been also observed in the fine structure and peak intensities of the nitrogen K-edge. These alterations are suggestive of differences in the maturation of collagen nucleation sites or cross-links. Future studies will aim to establish the scale and impact of the modifications observed in oimtissues. The compositional and structural alterations at the molecular level cause deficiencies at larger length scales. Understanding the effect of molecular alterations to pathologic bone is critical to the design of effective therapeutics.

Aurivillius structured Bi6Ti3Fe1.5Mn0.5O18(B6TFMO) has emerged as a rare room temperature multiferroic, exhibiting reversible magnetoelectric switching of ferroelectric domains under cycled magnetic fields. This layered oxide presents exceptional avenues for advancing data storage technologies owing to its distinctive ferroelectric and ferrimagnetic characteristics. Despite its immense potential, a comprehensive understanding of the underlying mechanisms driving multiferroic behavior remains elusive. Herein, we employ atomic resolution electron microscopy to elucidate the interplay of octahedral tilting and atomic-level structural distortions within B6TFMO, associating these phenomena with functional properties. Fundamental electronic features at varying bonding environments within this complex system are scrutinized using electron energy loss spectroscopy (EELS), revealing that the electronic nature of the Ti4+cations within perovskite BO6octahedra is influenced by position within the Aurivillius structure. Layer-by-layer EELS analysis shows an ascending crystal field splitting (Δ) trend from outer to center perovskite layers, with an average increase in Δ of 0.13 ± 0.06 eV. Density functional theory calculations, supported by atomic resolution polarization vector mapping of B-site cations, underscore the correlation between the evolving nature of Ti4+cations, the extent of tetragonal distortion and ferroelectric behavior. Integrated differential phase contrast imaging unveils the position of light oxygen atoms in B6TFMO for the first time, exposing an escalating degree of octahedral tilting toward the center layers, which competes with the magnitude of BO6tetragonal distortion. The observed octahedral tilting, influenced by B-site cation arrangement, is deemed crucial for juxtaposing magnetic cations and establishing long-range ferrimagnetic order in multiferroic B6TFMO.

Since the approval of the lipid nanoparticles (LNP)-mRNA vaccines against the SARS-CoV-2 virus, there has been an increased interest in the delivery of mRNA through LNPs. However, current LNP formulations contain PEG lipids, which can stimulate the generation of anti-PEG antibodies. The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration. Given the widespread deployment of the COVID-19 vaccines, the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components. In this study, we investigated a series of polysarcosine (pSar) lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems. We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.

Electrical detection of topological magnetic textures such as skyrmions is currently limited to conducting materials. Although magnetic insulators offer key advantages for skyrmion technologies with high speed and low loss, they have not yet been explored electrically. Here, we report a prominent topological Hall effect in Pt/Tm3Fe5O12bilayers, where the pristine Tm3Fe5O12epitaxial films down to 1.25 unit cell thickness allow for tuning of topological Hall stability over a broad range from 200 to 465 K through atomic-scale thickness control. Although Tm3Fe5O12is insulating, we demonstrate the detection of topological magnetic textures through a novel phenomenon: “spin-Hall topological Hall effect” (SH-THE), where the interfacial spin–orbit torques allow spin-Hall-effect generated spins in Pt to experience the unique topology of the underlying skyrmions in Tm3Fe5O12. This novel electrical detection phenomenon paves a new path for utilizing a large family of magnetic insulators in future skyrmion technologies.

The creation of 2D van der Waals materials with ferromagnetism above room temperature is an essential goal toward their practical utilization in spin-based applications. Recent studies suggest that intercalating lithium in exfoliated flakes of the ferromagnet Fe3–xGeTe2induces a nonzero magnetization at T∼ 300 K. However, the nanoscale nature of such experiments precludes precise observations of structural and chemical changes upon intercalation. Here, we report the preparation of sodium-intercalated NaFe2.78GeTe2as well as the investigation into its structure and magnetic properties. Sodium readily intercalates into the van der Waals gap, as revealed by synchrotron X-ray diffraction. Concurrently, the Fe2.78GeTe2layer becomes heavily charge doped and strained via chemical pressure, yet retains its structure and ferromagnetic transition temperature of ∼140 K. However, we observe the presence of a ferromagnetic amorphous iron germanide impurity over a wide range of synthetic conditions, leading to room-temperature magnetization. This work highlights the importance of strain and electronic control for manipulating the Curie temperature in 2D ferromagnets, while emphasizing the need for careful chemical analysis when exploring phenomena in exfoliated layers.

Here we demonstrate a new monoclinic iron oxide phase (μ-Fe2O3), epitaxially stabilized by growth on (010) β-Ga2O3. Density functional theory (DFT) calculations find that the lattice parameters of freestanding μ-Fe2O3are within ∼1% of those of β-Ga2O3, and that its energy of formation is comparable to that of naturally abundant Fe2O3polytypes. A superlattice of μ-Fe2O3/β-Ga2O3is grown by plasma assisted molecular beam epitaxy, with resulting high-resolution X-ray diffraction (XRD) measurements indicating that the μ-Fe2O3layers are lattice-matched to the substrate. The measured out-of-plane (b) lattice parameter of 3.12 ± 0.4 Å is in agreement with the predicted lattice constants and atomic-resolution scanning transmission electron microscopy (STEM) images confirm complete registry of the μ-Fe2O3layers with β-Ga2O3. Finally, DFT modeling predicts that bulk μ-Fe2O3is antiferromagnetic, while the interface region between μ-Fe2O3and β-Ga2O3leads to ferromagnetic coupling between interface Fe3+cations selectively occupying tetrahedral positions. Magnetic hysteresis persisting to room temperature is observed via SQUID measurements, consistent with the computationally predicted interface magnetism.

Skyrmion imaging and electrical detection via topological Hall (TH) effect are two primary techniques for probing magnetic skyrmions, which hold promise for next-generation magnetic storage. However, these two kinds of complementary techniques have rarely been employed to investigate the same samples. We report the observation of nanoscale skyrmions in SrIrO3/SrRuO3(SIO/SRO) bilayers in a wide temperature range from 10 to 100 K. The SIO/SRO bilayers exhibit a remarkable TH effect, which is up to 200% larger than the anomalous Hall (AH) effect at 5 K, and zero-field TH effect at 90 K. Using variable-temperature, high-field magnetic force microscopy (MFM), we imaged skyrmions as small as 10 nm, which emerge in the same field ranges as the TH effect. These results reveal a rich space for skyrmion exploration and tunability in oxide heterostructures.

Controlling magnetism with electric field directly or through strain-driven piezoelectric coupling remains a key goal of spintronics. Here, we demonstrate that giant piezomagnetism, a linear magneto-mechanic coupling effect, is manifest in antiperovskite Mn3NiN, facilitated by its geometrically frustrated antiferromagnetism opening the possibility of new memory device concepts. Films of Mn3NiN with intrinsic biaxial strains of ±0.25% result in Néel transition shifts up to 60 K and magnetization changes consistent with theory. Films grown on BaTiO3display a striking magnetization jump in response to uniaxial strain from the intrinsic BaTiO3structural transition, with an inferred 44% strain coupling efficiency and a magnetoelectric coefficient α (where α = dB/dE) of 0.018 G cm/V. The latter agrees with the 1000-fold increase over Cr2O3predicted by theory. Overall, our observations pave the way for further research into the broader family of Mn-based antiperovskites where yet larger piezomagnetic effects are predicted to occur at room temperature.

Abstract

Lipid nanoparticle (LNP)-mediated delivery of messenger RNA (mRNA) COVID-19 vaccines has provided large-scale immune protection to the public. To elicit a robust immune response against SARS-CoV-2 infections, antigens produced by mRNAs encoding SARS-CoV-2 Spike glycoprotein need to be efficiently delivered and presented to antigen-presenting cells such as dendritic cells (DCs). As concurrent innate immune stimulation can facilitate the antigen presentation process, a library of non-nucleotide STING agonist-derived amino lipids (SALs) was synthesized and formulated into LNPs for mRNA delivery. SAL12 lipid nanoparticles (SAL12-LNPs) were identified as most potent in delivering mRNAs encoding the Spike glycoprotein (S) of SARS-CoV-2 while activating the STING pathway in DCs. Two doses of SAL12 S-LNPs by intramuscular immunization elicited potent neutralizing antibodies against SARS-CoV-2 in mice.

There is a diverse family of palladium selenide compounds, including semiconducting orthorhombic PdSe2(O-PdSe2) and monoclinic PdSe2(M-PdSe2), which are unusual among transition-metal dichalcogenides as they are composed of diselenide dianions Se22–. Thus far, the solution syntheses of materials with Se–Se bonds typically require the in situ reduction of Se precursors. Here, we explore the use of electrochemically precise reactions between Na2Se2and a Pd2+source, Na2PdCl4, as a solution-phase route to selectively form different PdSe2polymorphs in the absence of surfactants. By altering the reactant molar ratios and time, we map out a synthetic phase space diagram that shows how to create a wide variety of palladium selenide phases. With increasing Se22–/Pd2+molar ratios, regions are identified where Pd17Se15, M-PdSe2, and O-PdSe2exist as the dominant or exclusive thermodynamic product. Additionally, we discover Pd3Se10, a superatomic crystal composed of Pd6Se20cube-shaped clusters held together by van der Waals forces, which forms as a kinetic product under short reaction times. In total, the use of the diselenide dianion precursor allows for the selective solution-phase synthesis of M-PdSe2or O-PdSe2, as well as the discovery of a previously unreported palladium selenide phase.

The discovery of new families of exfoliatable 2D crystals that have diverse sets of electronic, optical, and spin–orbit coupling properties enables the realization of unique physical phenomena in these few-atom-thick building blocks and in proximity to other materials. Herein, using NaSn2As2as a model system, we demonstrate that layered Zintl phases having the stoichiometry ATt2Pn2(A = group 1 or 2 element, Tt = group 14 tetrel element, and Pn = group 15 pnictogen element) and feature networks separated by van der Waals gaps can be readily exfoliated with both mechanical and liquid-phase methods. We identified the symmetries of the Raman-active modes of the bulk crystals viapolarized Raman spectroscopy. The bulk and mechanically exfoliated NaSn2As2samples are resistant toward oxidation, with only the top surface oxidizing in ambient conditions over a couple of days, while the liquid-exfoliated samples oxidize much more quickly in ambient conditions. Employing angle-resolved photoemission spectroscopy, density functional theory, and transport on bulk and exfoliated samples, we show that NaSn2As2is a highly conducting 2D semimetal, with resistivities on the order of 10–6Ω·m. Due to peculiarities in the band structure, the dominating p-type carriers at low temperature are nearly compensated by the opening of n-type conduction channels as temperature increases. This work further expands the family of exfoliatable 2D materials to layered van der Waals Zintl phases, opening up opportunities in electronics and spintronics.

A multilayered film of BaTiO3/SrTiO3was grown on a LaAlO3substrate using dual-target pulsed laser deposition technique. High-resolution scanning transmission electron microscopy observations show that the nine unit-cell BaTiO3layer and the three unit-cell SrTiO3layer are alternatively arranged in the epitaxial film where a sharp interface exists between the BaTiO3and SrTiO3layers. Electron energy-loss spectroscopy analysis demonstrates that the O-Kedge spectra of SrTiO3and BaTiO3layers are quite distinct; in particular, the energy-loss peak at 547 eV in the SrTiO3spectrum splits into two peaks in the BaTiO3spectrum. The multiple-scattering calculations of O-Kedge spectra for BaTiO3and SrTiO3agree well with the experimental results. The low-energy region (<542 eV) of the O-Kedge spectra for both BaTiO3and SrTiO3is mainly caused by the hybridization of the O 2p with Ti 3d orbitals. The splitting peaks between 542 and 552 eV in the O-Kedge spectra of BaTiO3are attributed to its complex crystal structure including two unequal oxygen sites and low site symmetry.

The degradation of intermediate temperature solid oxide fuel cell (ITSOFC) cathodes has been identified as a major issue limiting the development of ITSOFCs as high efficiency energy conversion devices. In this work, the effect of Cr poisoning on (La0.6Sr0.4)0.95(Co0.2Fe0.8)O3-δ(LSCF6428), a particularly promising ITSOFC cathode material, was investigated on symmetrical cells using electrochemical impedance spectroscopy and multiscale structural/chemical analysis by advanced electron and ion microscopy. The systematic combination of bulk and high-resolution analysis on the same cells allows, for the first time, direct correlation of Cr induced performance degradation with subtle and localized structural/chemical changes of the cathode down to the atomic scale. Up to 2 orders of magnitude reduction in conductivity, oxygen surface exchange rate, and diffusivity were observed in Cr poisoned LSCF6428 samples. These effects are associated with the formation of nanometer size SrCrO4; grain boundary segregation of Cr; enhanced B-site element exsolution (both Fe and Co); and reduction in the Fe valence, the latter two being related to Cr substitution in LSCF. The finding that significant degradation of the cathode happens before obvious microscale change points to new critical SOFC degradation mechanisms effective at the nanometer scale and below.

Electron channeling contrast imaging (ECCI) is a nondestructive diffraction-based scanning electron microscopy (SEM) technique that can provide microstructural analysis similar to transmission electron microscopy (TEM). However, because ECCI is performed within an SEM and requires little to no sample preparation, such analysis can be accomplished in a fraction of the time. Like TEM, ECCI can be used to image a variety of extended defects and enables the use of standard invisibility criteria to provide further defect characterization (e.g., Burgers vector determination). Here, we use ECCI to characterize various extended defects, including threading dislocations, misfit dislocations, and stacking faults, in heteroepitaxial GaP/Si(1 0 0) samples. We also present applications for which ECCI is particularly well suited compared with conventional methods. First, misfit dislocations are surveyed via ECCI across the radius of a 4-in GaP/Si wafer, yielding a proof-of-concept rapid (~3 h) approach to large-area defect characterization. Second, by simply wet etching away a portion of a thick epitaxial GaP-on-Si layer, we use ECCI to image specific targeted interfaces within a heterostructure. Both of these applications are prime examples of how ECCI is a compelling alternative to TEM in circumstances where the required sample preparation would be prohibitively time-consuming or difficult.

Functionalized Extracellular Vesicles In article number 2100805by Natalia Higuita‐Castro and co‐workers, designer extracellular vesicles (EVs) are manufactured via non‐viral engineering of donor cells through electroporation. Designer EVs are packed with plasmid DNA, mRNA, and protein content. Transfecting donor cells with expression plasmids for membrane proteins can be used to tailor the surface decoration of the EVs. Pro‐neurogenic designer EVs drive neurogenesis and improve targeting of neuronal tissue, in vitro and in vivo.