Publications
330 results found
Zhang Y, Yan J, Hou X, et al., 2023, STING Agonist-Derived LNP-mRNA Vaccine Enhances Protective Immunity Against SARS-CoV-2., Nano Lett, Vol: 23, Pages: 2593-2600
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.
Du S, Li W, Zhang Y, et al., 2023, Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice., Adv Sci (Weinh), Vol: 10
Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.
Colby R, Williams REA, Carpenter DL, et al., 2023, Identifying and imaging polymer functionality at high spatial resolution with core-loss EELS., Ultramicroscopy, Vol: 246
Electron energy loss spectroscopy (EELS) is a proven tool for probing materials chemistry at high spatial resolution. Core-loss EELS fine structure should allow measurement of local polymer chemistry. For organic materials, sensitivity to radiolysis is expected to limit the resolution achievable with EELS: but core-loss EELS has proven difficult at any resolution, yielding inconsistent spectra that compare unfavorably with theoretically analogous x-ray absorption spectra. Many of the previously identified shortcomings should not be limiting factors on modern equipment. This study establishes that EELS can generate identifiable carbon K-edge spectra for a range of common polymer types and chemistry, and demonstrates fine structure features matching prior x-ray absorption spectra. EELS fine structure features broaden intuitively with the instrument's energy resolution, and beam-induced features are readily differentiated by collecting spectra at a series of doses. The results are demonstrated with spectrum images of a model polymer blend, and used to estimate practical pixel sizes that can be used for mapping core-loss EELS as a function of electron dose.
Rincon-Benavides MA, Mendonca NC, Cuellar-Gaviria TZ, et al., 2023, Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure, Advanced Therapeutics, Vol: 6
Vasculogenic cell therapies have emerged as a powerful tool to increase vascularization and promote tissue repair/regeneration. Current approaches to cell therapies, however, rely mostly on progenitor cells, which pose significant risks (e.g., uncontrolled differentiation, tumorigenesis, and genetic/epigenetic abnormalities). Moreover, reprogramming methodologies used to generate induced endothelial cells (iECs) from induced pluripotent stem cells rely heavily on viral vectors, which pose additional translational limitations. This work describes the development of engineered human extracellular vesicles (EVs) capable of driving reprogramming-based vasculogenic therapies without the need for progenitor cells and/or viral vectors. EVs are derived from primary human dermal fibroblasts (HDFs), and are engineered to pack transcription factor genes/transcripts of ETV2, FLI1, and FOXC2 (EFF). In addition to EFF, the engineered EVs are also loaded with transcripts of angiogenic factors (e.g., VEGF-A, VEGF-KDR, FGF2). In vitro and in vivo studies indicate that such EVs effectively transfected HDFs and drive direct conversions towards iECs within 714 days. Finally, wound healing studies in mice indicate that engineered EVs lead to improved wound closure and vascularity. Altogether, these results show the potential of engineered human vasculogenic EVs to drive direct reprogramming processes of somatic cells towards iECs, and facilitate tissue repair/regeneration.
Wang B, McComb DW, 2023, Phase imaging in scanning transmission electron microscopy using bright-field balanced divergency method., Ultramicroscopy, Vol: 245
We introduce a phase imaging mechanism for scanning transmission electron microscopy that exploits the complementary intensity changes of transmitted disks at different scattering angles. For scanning transmission electron microscopy, this method provides a straightforward, dose-efficient, and noise-robust phase imaging, from atomic resolution to intermediate length scales, as a function of scattering angles and probe defocus. At atomic resolution, we demonstrate that the phase imaging using the method can detect both light and heavy atomic columns. Furthermore, we experimentally apply the method to the imaging of nanoscale magnetic phases in FeGe samples. Compared with conventional methods, phase retrieval using the new method has higher effective spatial resolution and robustness to non-phase background contrast. Our method complements traditional phase imaging modalities in electron microscopy and has the potential to be extended to other scanning transmission techniques and to characterize many emerging material systems.
Brennan MC, Veghte DP, Ford BR, et al., 2023, Photolysis of Mixed Halide Perovskite Nanocrystals, ACS Energy Letters, Pages: 2150-2158
Colloidal mixed halide perovskite nanocrystals (NCs) irreversibly degrade when exposed to ultraviolet-visible irradiation. Here, mixed halide perovskite NC photolysis is tracked via mass spectrometry, electron microscopy, and photoluminescence. The data shows continuous wave ultraviolet-visible irradiation causes the heavier halides within the alloy to sublimate. This ultimately transforms CsPb(I1-xBrx)3 and CsPb(Cl1-xBrx)3 (x ≈ 0.50) NCs into CsPbBr3 and CsPbCl3 NCs, respectively. Time-resolved mass spectrometry demonstrates real-time desorption of volatile halide species (e.g., I2(g)/HI(g)) during irradiation. Energy-dispersive X-ray spectroscopy confirms near complete expulsion of I- from CsPb(I1-xBrx)3 and Br- from CsPb(Cl1-xBrx)3 NCs. Electron diffraction and cathodoluminescence establish lattice contractions and emission blueshifts consistent with formation of single halide perovskites from parent mixed halide alloys. Finally, increasing photolysis rates at higher temperatures follow an Arrhenius relationship with an effective activation energy of ∼62 kJ mol-1 for CsPb(I1-xBrx)3 NCs (x ≈ 0.50). Altogether, this work provides important insight into the photolysis of colloidal perovskite NC alloys.
Sternlicht H, McComb DW, Padture NP, 2022, Interaction of ytterbium pyrosilicate environmental-barrier-coating ceramics with molten calcia-magnesia-aluminosilicate glass: Part II, Interfaces, Acta Materialia, Vol: 241, ISSN: 1359-6454
Interfaces in as-processed β-Yb2Si2O7 environmental barrier coating (EBC) ceramics, and those after high-temperature (1500 °C) interaction with a calcia-magnesia-aluminosilicate (CMAS) glass from Part I are studied in further detail using high-resolution transmission electron microscopy (HRTEM), annular dark field scanning TEM (ADF STEM) and high-angle ADF (HAADF) STEM. Disconnections are detected, or inferred, at twin and general grain-boundaries and also at phase boundaries. Grain-boundary and facet planes are found to be aligned parallel to {110} planes of β-Yb2Si2O7. When detected, step planes are also found to be aligned parallel to β-Yb2Si2O7 {110} planes. At the same time, the dislocation component has major projections aligned parallel to {110} planes of β-Yb2Si2O7. As such, both the step and the dislocation components of the disconnections are anisotropic. The tendency of the grain-boundary and facet planes at interfaces in the system to align parallel to β-Yb2Si2O7{110} planes, both before and after CMAS-interaction, is discussed. The chemistry of grain-boundaries in the vicinity of the disconnections is found to be non-stoichiometric, but this by itself cannot account for the extended contrast variations along twin boundaries. Thus, contrast variations along grain boundaries are associated mainly with the presence of disconnections and associated strain, as well as long-range distortions in the unit cells in twin boundaries. These anisotropic disconnections are associated with the mechanisms of grain-boundary and phase-boundary migration, and thus, they have implications on the evolution of microstructures in this system. Combined insights from Part I and this Part II elucidate the nature of the interfaces in β-Yb2Si2O7 EBC ceramic and the mechanisms of CMAS glass penetration.
Hettiaratchy EC, Wang B, Dheenan A, et al., 2022, Quantitative x-ray diffraction analysis of strain and interdiffusion in β-Ga<inf>2</inf>O<inf>3</inf>superlattices of μ -Fe<inf>2</inf>O<inf>3</inf>and β-(Al<inf>x</inf>Ga<inf>1-x</inf>)<inf>2</inf>O<inf>3</inf>, Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films, Vol: 40, ISSN: 0734-2101
Superlattices composed of either monoclinic μ-Fe2O3 or β-(AlxGa1-x)2O3 with β-Ga2O3 spacers are grown on (010) β-Ga2O3 substrates using plasma-assisted molecular beam epitaxy. High-resolution x-ray diffraction data are quantitatively fit using commercial dynamical x-ray diffraction software (LEPTOS) to obtain layer thicknesses, strain, and compositions. The strain state of β-(AlxGa1-x)2O3 and μ-Fe2O3 superlattices as characterized using reciprocal space maps in the symmetric (020) and asymmetric (420) diffraction conditions indicates coherent growths that are strained to the (010) β-Ga2O3 lattice. β-(AlxGa1-x)2O3 and μ-Fe2O3 superlattices grown at hotter substrate temperatures result in crystal structures with better coherency and reduced defects compared to colder growths. The growth rate of μ-Fe2O3 is ∼2.6 nm/min at Tsub = 700 °C and drops to ∼1.6 nm/min at Tsub = 800 °C due to increased Fe interdiffusion at hotter substrate temperatures. Scanning transmission electron microscopy data of a μ-Fe2O3 superlattice grown at Tsub = 700 °C confirm that there is significant diffusion of Fe atoms into β-Ga2O3 layers.
Sternlicht H, McComb DW, Padture NP, 2022, Interaction of ytterbium pyrosilicate environmental-barrier-coating ceramics with molten calcia-magnesia-aluminosilicate glass: Part I, Microstructures, Acta Materialia, Vol: 241, ISSN: 1359-6454
Ytterbium pyrosilicate (or disilicate; β-Yb2Si2O7) is a promising ceramic for environmental barrier coatings (EBCs) for ceramic-matrix composite (CMC) components in the hot-section of gas-turbine engines. In addition to the various requirements an EBC must satisfy, it must be resistant to high-temperature attack by calcia-magnesia-aluminosilicates (CMASs) ingested by the engine in the form of sand, dust, ash, etc. Here, the microstructures of dense, polycrystalline β-Yb2Si2O7 EBC ceramics, before and after high-temperature (1500 °C) interaction with a representative CMAS glass, are characterized, primarily using scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), and electron energy loss spectroscopy (EELS). Since actual EBCs are dense and polycrystalline, sintered pellets of EBC ceramics serve as acceptable proxies for such basic studies. It is confirmed that the CMAS glass wets certain grain boundaries in β-Yb2Si2O7 ceramics, and the mechanisms associated with the penetration of the CMAS glass are elucidated. It is also found that secondary-phase inclusions, that are ubiquitously present in these ceramics, but rarely characterized, are either rounded or faceted. The relatively large, partially-faceted ones are invariably attached to the grain boundaries, and can contain crystalline X2-Yb2SiO5 and Yb2O3, and amorphous SiO2 secondary phases primarily. However, after high-temperature CMAS interaction, these inclusions become occluded within β-Yb2Si2O7 grains, and are filled with Yb-containing CMAS glass. All these new findings contribute towards the broader understanding of β-Yb2Si2O7/CMAS interactions, with implications for the design of EBC microstructures and approaches to mitigate CMAS-induced degradation in EBCs. The accompanying Part II paper presents results from extensive characterization at the atomistic level, and addresses the anisotropic nature of the interfaces in the system, as well as defec
Liu Q, Hoefer N, Berkbigler G, et al., 2022, Strong CO2 Chemisorption in a Metal-Organic Framework with Proximate Zn-OH Groups., Inorg Chem, Vol: 61, Pages: 18710-18718
A novel Zn benzotriazolate metal-organic framework (MOF), [Zn9(OAc)6(bbtm)6] (1, bbtm2- = bis(benzotriazolyl)methanone, OAc- = acetate), has been synthesized and structurally characterized using micro-crystal electron diffraction. The framework contains 12-connected nonanuclear Zn clusters with Zn-OAc groups separated by short intercluster Zn···Zn distances of 6.06 Å. Postsynthetic OAc-/OH- ligand exchange followed by thermal activation generates 1a-OH, which adsorbs CO2 at very low pressures (1.37 mmol/g at 2.5 mbar) and requires an unusually high desorption temperature (>160 °C). Diffuse reflectance IR Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations have been used to interrogate the CO2 binding mechanism in 1a-OH. The formation of unsymmetric bridging carbonate ligands within the Zn···Zn pockets accompanied by strong hydrogen bonding of the carbonate with a neighboring zinc aqua ligand explains the remarkably strong CO2 affinity of 1a-OH.
Yan J, Zhang Y, Du S, et al., 2022, Nanomaterials-Mediated Co-Stimulation of Toll-Like Receptors and CD40 for Antitumor Immunity., Adv Mater, Vol: 34
Toll-like receptors (TLRs) and CD40-related signaling pathways represent critical bridges between innate and adaptive immune responses. Here, an immunotherapy regimen that enables co-stimulation of TLR7/8- and CD40-mediated pathways is developed. TLR7/8 agonist resiquimod (R848) derived amino lipids, RAL1 and RAL2, are synthesized and formulated into RAL-derived lipid nanoparticles (RAL-LNPs). The RAL2-LNPs show efficient CD40 mRNA delivery to DCs both in vitro (90.8 ± 2.7%) and in vivo (61.3 ± 16.4%). When combined with agonistic anti-CD40 antibody, this approach can produce effective antitumor activities in mouse melanoma tumor models, thereby suppressing tumor growth, prolonging mouse survival, and establishing antitumor memory immunity. Overall, RAL2-LNPs provide a novel platform toward cancer immunotherapy by integrating innate and adaptive immunity.
Pavlović RZ, Zhiquan L, Finnegan TJ, et al., 2022, Closed Aromatic Tubes-Capsularenes., Angew Chem Int Ed Engl, Vol: 61
In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase-shaped molecular baskets 4-7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of 4, 6 and 7 change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5-trioxane (1 H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes 1 (0.7×0.9 nm), 8 (0.7×1.1 nm;) and 9 (0.7×1.4 nm;) characterized by X-Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices.
Ma D, Deng B, Sun C, et al., 2022, The Mechanical Microenvironment Regulates Axon Diameters Visualized by Cryo-Electron Tomography., Cells, Vol: 11
Axonal varicosities or swellings are enlarged structures along axon shafts and profoundly affect action potential propagation and synaptic transmission. These structures, which are defined by morphology, are highly heterogeneous and often investigated concerning their roles in neuropathology, but why they are present in the normal brain remains unknown. Combining confocal microscopy and cryo-electron tomography (Cryo-ET) with in vivo and in vitro systems, we report that non-uniform mechanical interactions with the microenvironment can lead to 10-fold diameter differences within an axon of the central nervous system (CNS). In the brains of adult Thy1-YFP transgenic mice, individual axons in the cortex displayed significantly higher diameter variation than those in the corpus callosum. When being cultured on lacey carbon film-coated electron microscopy (EM) grids, CNS axons formed varicosities exclusively in holes and without microtubule (MT) breakage, and they contained mitochondria, multivesicular bodies (MVBs), and/or vesicles, similar to the axonal varicosities induced by mild fluid puffing. Moreover, enlarged axon branch points often contain MT free ends leading to the minor branch. When the axons were fasciculated by mimicking in vivo axonal bundles, their varicosity levels reduced. Taken together, our results have revealed the extrinsic regulation of the three-dimensional ultrastructures of central axons by the mechanical microenvironment under physiological conditions.
Hsu YH, Trout A, Bartlett JD, et al., 2022, MMP20-Ablated Induced Aberrant Mineralization in Early Secretory Enamel, Microscopy and Microanalysis, Vol: 28, Pages: 1356-1358, ISSN: 1431-9276
Trout AH, Kurfman SW, Shi Y, et al., 2022, Probing the structure of vanadium tetracyanoethylene using electron energy-loss spectroscopy, APL Materials, Vol: 10
The molecule-based ferrimagnetic semiconductor vanadium tetracyanoethylene (V[TCNE]x, x ≈ 2) has garnered interest from the quantum information community due to its excellent coherent magnonic properties and ease of on-chip integration. Despite these attractive properties, a detailed understanding of the electronic structure and mechanism for long-range magnetic ordering have remained elusive due to a lack of detailed atomic and electronic structural information. Previous studies via x-ray absorption near edge spectroscopy and the extended x-ray absorption fine structure have led to various proposed structures, and in general, V[TCNE]x is believed to be a three-dimensional network of octahedrally coordinated V2+, each bonded to six TCNE molecules. Here, we elucidate the electronic structure, structural ordering, and degradation pathways of V[TCNE]x films by correlating calculations of density functional theory (DFT) with scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) of V[TCNE]x films. Low-loss EELS measurements reveal a bandgap and an excited state structure that agree quantitatively with DFT modeling, including an energy splitting between apical and equatorial TCNE ligands within the structure, providing experimental results directly backed by theoretical descriptions of the electronic structure driving the robust magnetic ordering in these films. Core-loss EELS confirms the presence of octahedrally coordinated V+2 atoms. Upon oxidation, changes in the C1s-π∗ peak indicate that C=C of TCNE is preferentially attacked. Furthermore, we identify a relaxation of the structural ordering as the films age. These results lay the foundation for a more comprehensive and fundamental understanding of magnetic ordering and dynamics in these classes of metal-ligand compounds.
Hassan A, Kennedy WJ, Koerner H, et al., 2022, Probing Changes in the Electronic Structure and Chemical Bonding of Ti<inf>3</inf>C<inf>2</inf>MXene Sheets with Electron Energy-Loss Spectroscopy, Microscopy and Microanalysis, Vol: 28, Pages: 1750-1751, ISSN: 1431-9276
Cheng S, Wang B, Lyalin I, et al., 2022, Atomic layer epitaxy of kagome magnet Fe<inf>3</inf>Sn<inf>2</inf>and Sn-modulated heterostructures, APL Materials, Vol: 10
Magnetic materials with kagome crystal structure exhibit rich physics, such as frustrated magnetism, skyrmion formation, topological flat bands, and Dirac/Weyl points. Until recently, most studies on kagome magnets have been performed on bulk crystals or polycrystalline films. Here, we report the atomic layer molecular beam epitaxy synthesis of high-quality thin films of topological kagome magnet Fe3Sn2. The structural and magnetic characterization of Fe3Sn2 on epitaxial Pt(111) identifies highly ordered films with c-plane orientation and an in-plane magnetic easy axis. Studies on the local magnetic structure by anomalous Nernst effect imaging reveal in-plane oriented micrometer size domains. Superlattice structures consisting of Fe3Sn2 and Fe3Sn are also synthesized by atomic layer molecular beam epitaxy, demonstrating the ability to modulate the sample structure at the atomic level. The realization of high-quality films by atomic layer molecular beam epitaxy opens the door to explore the rich physics of this system and investigate novel spintronic phenomena by interfacing Fe3Sn2 with other materials.
Liu J-Q, Zhang C, Zhang X, et al., 2022, Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy., J Control Release, Vol: 345, Pages: 306-313
Cytokines are important immunotherapeutics with approved drugs for the treatment of human cancers. However, systemic administration of cytokines often fails to achieve adequate concentrations to immune cells in tumors due to dose-limiting toxicity. Thus, developing localized therapy that directly delivers immune-stimulatory cytokines to tumors may improve the therapeutic efficacy. In this study, we generated novel lipid nanoparticles (LNPs) encapsulated with mRNAs encoding cytokines including IL-12, IL-27 and GM-CSF, and tested their anti-tumor activity. We first synthesized ionizable lipid materials containing di-amino groups with various head groups (DALs). The novel DAL4-LNP effectively delivered different mRNAs in vitro to tumor cells and in vivo to tumors. Intratumoral injection of DAL4-LNP loaded with IL-12 mRNA was most potent in inhibiting B16F10 melanoma tumor growth compared to IL-27 or GM-CSF mRNAs in monotherapy. Furthermore, intratumoral injection of dual DAL4-LNP-IL-12 mRNA and IL-27 mRNA showed a synergistic effect in suppressing tumor growth without causing systematic toxicity. Most importantly, intratumoral delivery of IL-12 and IL-27 mRNAs induced robust infiltration of immune effector cells, including IFN-γ and TNF-α producing NK and CD8+ T cells into tumors. Thus, intratumoral administration of DAL-LNP loaded with IL-12 and IL-27 mRNA provides a new treatment strategy for cancer.
Ortega-Pineda L, Sunyecz A, Salazar-Puerta AI, et al., 2022, Designer Extracellular Vesicles Modulate Pro-Neuronal Cell Responses and Improve Intracranial Retention., Adv Healthc Mater, Vol: 11
Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1, Brn2, and Myt1l (ABM) are found to show enhanced neuron-specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro-neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM-loaded designer EVs can be a promising platform nanotechnology to drive pro-neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.
Wang B, Bagués N, Liu T, et al., 2022, Extracting weak magnetic contrast from complex background contrast in plan-view FeGe thin films., Ultramicroscopy, Vol: 232
The desire to design and build skyrmion-based devices has led to the need to characterize magnetic textures in thin films of functional materials. This can usually be achieved through the Lorentz transmission electron microscopy (LTEM) and the Lorentz scanning transmission electron microscopy (LSTEM) in thin film cross-section and single crystal specimens. However, direct imaging of the magnetic texture in plan-view samples of thin (< 50 nm) films has proved to be challenging due to the complex "background" contrast associated with the microstructure and defects, as well as contributions from bending of the specimens. Using a mechanically polished 35 nm plan-view FeGe thin film, we have explored three methods to extract magnetic contrast from the complex background contrast observed; (1) background subtraction in defocused LTEM images, (2) frequency filtered CoM-DPC reconstructed from LSTEM datasets and 3) registration of 4D-STEM datasets acquired at different tilt angles. Using these methods, we have successfully implemented real space imaging of both the helical phase and skyrmion phase. The ability to understand nanoscale magnetic behavior from plan-view thin films is a fundamental step towards development of highly integrated spin electronics.
Li W, Zhang X, Zhang C, et al., 2021, Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy., Nat Commun, Vol: 12
Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.
Zhao W, Zeng C, Yan J, et al., 2021, Construction of Messenger RNA (mRNA) Probes Delivered By Lipid Nanoparticles to Visualize Intracellular Protein Expression and Localization at Organelles., Adv Mater, Vol: 33
Organelles are specialized compartments, where various proteins reside and play crucial roles to maintain essential cellular structures and functions in mammalian cells. A comprehensive understanding of protein expressions and subsequent localizations at each organelle is of great benefit to the development of organelle-based therapies. Herein, a set of single or dual organelle labeling messenger RNAs (SOLAR or DOLAR) is designed as novel imaging probes, which encode fluorescent proteins with various organelle localization signals. These mRNA probes enable to visualize the protein localizations at different organelles and investigate their trafficking from ribosomal machinery to specific organelles. According to the in vitro results, SOLAR probes show organelle targeting capabilities consistent with the design. Moreover, DOLAR probes with different linkers display distinct targeting properties depending on different organelle localization signals. Additionally, these mRNA probes also exhibit organelle labeling ability in vivo when delivered by lipid nanoparticles (LNPs). Therefore, these mRNA-based probes provide a unique tool to study cell organelles and may facilitate the design of organelle-based therapies.
Wang B, Wu P-K, Bagués Salguero N, et al., 2021, Stimulated Nucleation of Skyrmions in a Centrosymmetric Magnet., ACS Nano, Vol: 15, Pages: 13495-13503
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.
Liu Y, Lee Y-U, Yi T, et al., 2021, Surgery and Sample Processing for Correlative Imaging of the Murine Pulmonary Valve., J Vis Exp
The underlying causes of heart valve related-disease (HVD) are elusive. Murine animal models provide an excellent tool for studying HVD, however, the surgical and instrumental expertise required to accurately quantify the structure and organization across multiple length scales have stunted its advancement. This work provides a detailed description of the murine dissection, en bloc staining, sample processing, and correlative imaging procedures for depicting the heart valve at different length scales. Hydrostatic transvalvular pressure was used to control the temporal heterogeneity by chemically fixing the heart valve conformation. Micro-computed tomography (µCT) was used to confirm the geometry of the heart valve and provide a reference for the downstream sample processing needed for the serial block face scanning electron microscopy (SBF-SEM). High-resolution serial SEM images of the extracellular matrix (ECM) were taken and reconstructed to provide a local 3D representation of its organization. µCT and SBF-SEM imaging methods were then correlated to overcome the spatial variation across the pulmonary valve. Though the work presented is exclusively on the pulmonary valve, this methodology could be adopted for describing the hierarchical organization in biological systems and is pivotal for the structural characterization across multiple length scales.
Trout AH, Hodge KL, Scudder M, et al., 2021, Low-Pressure Induced Disproportionation of Barium Distannide, Journal of Physical Chemistry C, Vol: 125, Pages: 15496-15502, ISSN: 1932-7447
Barium distannide (BaSn2), a potential precursor for stannene, is predicted to be a topological insulator. However, little is known about BaSn2 as the material is extremely air-sensitive. Here we present, for the first time, characterization of BaSn2 by scanning/transmission electron microscopy. We use advanced imaging and spectroscopy techniques to show disproportionation of BaSn2 particles into β-Sn + BaxSny. X-ray diffraction analysis confirms that this disproportionation is driven by exposure to a low-pressure environment.
Liu Y, Feng X, Liu H, et al., 2021, On the shape and structure of the murine pulmonary heart valve., Sci Rep, Vol: 11
Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. Results to date suggest that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.
Bartlett JD, Smith CE, Hu Y, et al., 2021, MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations., Sci Rep, Vol: 11
Dental enamel forms extracellularly as thin ribbons of amorphous calcium phosphate (ACP) that initiate on dentin mineral in close proximity to the ameloblast distal membrane. Secreted proteins are critical for this process. Enam-/- and Ambn-/- mice fail to form enamel. We characterize enamel ribbon formation in wild-type (WT), Amelx-/- and Mmp20-/- mouse mandibular incisors using focused ion beam scanning electron microscopy (FIB-SEM) in inverted backscatter mode. In Amelx-/- mice, initial enamel mineral ribbons extending from dentin are similar in form to those of WT mice. As early enamel development progresses, the Amelx-/- mineral ribbons develop multiple branches, resembling the staves of a Japanese fan. These striking fan-shaped structures cease growing after attaining ~ 20 µm of enamel thickness (WT is ~ 120 µm). The initial enamel mineral ribbons in Mmp20-/- mice, like those of the Amelx-/- and WT, extend from the dentin surface to the ameloblast membrane, but appear to be fewer in number and coated on their sides with organic material. Remarkably, Mmp20-/- mineral ribbons also form fan-like structures that extend to ~ 20 µm from the dentin surface. However, these fans are subsequently capped with a hard, disorganized outer mineral layer. Amelogenin cleavage products are the only matrix components absent in both Amelx-/- and Mmp20-/- mice. We conclude that MMP20 and amelogenin are not critical for enamel mineral ribbon initiation, orientation, or initial shape. The pathological fan-like plates in these mice may form from the lack of amelogenin cleavage products, which appear necessary to form ordered hydroxyapatite.
Hettiaratchy EC, Jamison JS, Wang B, et al., 2020, Interface-induced ferromagnetism in μ-Fe<inf>2</inf>O<inf>3</inf>/β-Ga<inf>2</inf>O<inf>3</inf>superlattices, Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films, Vol: 38, ISSN: 0734-2101
Superlattices of antiferromagnetic μ-Fe2O3 and diamagnetic β-Ga2O3 are grown by plasma-assisted molecular beam epitaxy on (010) oriented β-Ga2O3 substrates in which ferromagnetism emerges above room temperature. To investigate the suspected interface origin of the ferromagnetic phase, identical superlattice structures are grown at various substrate temperatures and beam fluxes. Atomic-resolution scanning transmission electron microscopy images confirm the registry of μ-Fe2O3 to the β-Ga2O3 layers in these superlattices. Atomic force microscopy and high-resolution x-ray diffraction are used to examine the growth morphology and characterize the superlattice interface roughness. The saturation magnetization of the ferromagnetic phase is observed to increase strongly with the interface roughness. Conversely, smoother superlattices exhibit a weaker ferromagnetic response and a higher density of paramagnetic moments along with evidence of superparamagnetic clusters. These findings are consistent with the interface origin for the ferromagnetic response in these superlattices. The demonstration of an interface magnetic phase in nearly lattice-matched monoclinic Fe2O3/Ga2O3 opens the door to ultrawide bandgap heterostructure-engineered magnetoelectronic devices, where ferromagnetic switching of the interface phase can be incorporated into high-field devices.
Zhang X, Zhao W, Nguyen GN, et al., 2020, Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing., Sci Adv, Vol: 6
Messenger RNA (mRNA) therapeutics have been explored to treat various genetic disorders. Lipid-derived nanomaterials are currently one of the most promising biomaterials that mediate effective mRNA delivery. However, efficiency and safety of this nanomaterial-based mRNA delivery remains a challenge for clinical applications. Here, we constructed a series of lipid-like nanomaterials (LLNs), named functionalized TT derivatives (FTT), for mRNA-based therapeutic applications in vivo. After screenings on the materials, we identified FTT5 as a lead material for efficient delivery of long mRNAs, such as human factor VIII (hFVIII) mRNA (~4.5 kb) for expression of hFVIII protein in hemophilia A mice. Moreover, FTT5 LLNs demonstrated high percentage of base editing on PCSK9 in vivo at a low dose of base editor mRNA (~5.5 kb) and single guide RNA. Consequently, FTT nanomaterials merit further development for mRNA-based therapy.
Hou X, Zhang X, Zhao W, et al., 2020, Author Correction: Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis., Nat Nanotechnol, Vol: 15
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.