ABSTRACT
Bacterial double-stranded DNA (dsDNA) cytosine deaminase DddAtox-derived cytosine base editor (DdCBE) and its evolved variant, DddA11, guided by transcription-activator-like effector (TALE) proteins, enable mitochondrial DNA (mtDNA) editing at TC or HC (H = A, C, or T) sequence contexts, while it remains relatively unattainable for GC targets. Here, we identified a dsDNA deaminase originated from a Roseburia intestinalis interbacterial toxin (riDddAtox) and generated CRISPR-mediated nuclear DdCBEs (crDdCBEs) and mitochondrial CBEs (mitoCBEs) using split riDddAtox, which catalyzed C-to-T editing at both HC and GC targets in nuclear and mitochondrial genes. Moreover, transactivator (VP64, P65, or Rta) fusion to the tail of DddAtox- or riDddAtox-mediated crDdCBEs and mitoCBEs substantially improved nuclear and mtDNA editing efficiencies by up to 3.5- and 1.7-fold, respectively. We also used riDddAtox-based and Rta-assisted mitoCBE to efficiently stimulate disease-associated mtDNA mutations in cultured cells and in mouse embryos with conversion frequencies of up to 58% at non-TC targets.
Subject(s)
Gene Editing , Trans-Activators , Mice , Animals , Trans-Activators/metabolism , Cytosine , Mutation , DNA, Mitochondrial/genetics , CRISPR-Cas SystemsABSTRACT
The convergence of topology and correlations represents a highly coveted realm in the pursuit of new quantum states of matter1. Introducing electron correlations to a quantum spin Hall (QSH) insulator can lead to the emergence of a fractional topological insulator and other exotic time-reversal-symmetric topological order2-8, not possible in quantum Hall and Chern insulator systems. Here we report a new dual QSH insulator within the intrinsic monolayer crystal of TaIrTe4, arising from the interplay of its single-particle topology and density-tuned electron correlations. At charge neutrality, monolayer TaIrTe4 demonstrates the QSH insulator, manifesting enhanced nonlocal transport and quantized helical edge conductance. After introducing electrons from charge neutrality, TaIrTe4 shows metallic behaviour in only a small range of charge densities but quickly goes into a new insulating state, entirely unexpected on the basis of the single-particle band structure of TaIrTe4. This insulating state could arise from a strong electronic instability near the van Hove singularities, probably leading to a charge density wave (CDW). Remarkably, within this correlated insulating gap, we observe a resurgence of the QSH state. The observation of helical edge conduction in a CDW gap could bridge spin physics and charge orders. The discovery of a dual QSH insulator introduces a new method for creating topological flat minibands through CDW superlattices, which offer a promising platform for exploring time-reversal-symmetric fractional phases and electromagnetism2-4,9,10.
ABSTRACT
Topology1-3 and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a 'hybrid' topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a conjoined strong and higher-order topology that stabilizes a hybrid topological phase. Although momentum-space spectroscopy measurements show signs of topological surface states, real-space microscopy measurements unravel a unique geometry of topologically induced step-edge conduction channels revealed on various natural nanostructures on the surface. Using theoretical models, we show that the existence of gapless step-edge states in arsenic relies on the simultaneous presence of both a non-trivial strong Z2 invariant and a non-trivial higher-order topological invariant, which provide experimental evidence for hybrid topology. Our study highlights pathways for exploring the interplay of different band topologies and harnessing the associated topological conduction channels in engineered quantum or nano-devices.
ABSTRACT
Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.
ABSTRACT
Phytohormone signalling pathways have an important role in defence against pathogens mediated by cell-surface pattern recognition receptors and intracellular nucleotide-binding leucine-rich repeat class immune receptors1,2 (NLR). Pathogens have evolved counter-defence strategies to manipulate phytohormone signalling pathways to dampen immunity and promote virulence3. However, little is known about the surveillance of pathogen interference of phytohormone signalling by the plant innate immune system. The pepper (Capsicum chinense) NLR Tsw, which recognizes the effector nonstructural protein NSs encoded by tomato spotted wilt orthotospovirus (TSWV), contains an unusually large leucine-rich repeat (LRR) domain. Structural modelling predicts similarity between the LRR domain of Tsw and those of the jasmonic acid receptor COI1, the auxin receptor TIR1 and the strigolactone receptor partner MAX2. This suggested that NSs could directly target hormone receptor signalling to promote infection, and that Tsw has evolved a LRR resembling those of phytohormone receptors LRR to induce immunity. Here we show that NSs associates with COI1, TIR1 and MAX2 through a common repressor-TCP21-which interacts directly with these phytohormone receptors. NSs enhances the interaction of COI1, TIR1 or MAX2 with TCP21 and blocks the degradation of corresponding transcriptional repressors to disable phytohormone-mediated host immunity to the virus. Tsw also interacts directly with TCP21 and this interaction is enhanced by viral NSs. Downregulation of TCP21 compromised Tsw-mediated defence against TSWV. Together, our findings reveal that a pathogen effector targets TCP21 to inhibit phytohormone receptor function, promoting virulence, and a plant NLR protein has evolved to recognize this interference as a counter-virulence strategy, thereby activating immunity.
Subject(s)
Capsicum , Plant Diseases , Plant Growth Regulators , Plant Immunity , Plant Proteins , Receptors, Pattern Recognition , Leucine , Plant Diseases/immunology , Plant Diseases/virology , Plant Growth Regulators/metabolism , Plant Immunity/immunology , Plant Proteins/chemistry , Plant Proteins/immunology , Plant Proteins/metabolism , Receptors, Pattern Recognition/chemistry , Receptors, Pattern Recognition/immunology , Receptors, Pattern Recognition/metabolism , Innate Immunity Recognition , Capsicum/immunology , Capsicum/metabolism , Capsicum/virology , VirulenceABSTRACT
Autoluminescent plants have been genetically modified to express the fungal bioluminescence pathway (FBP). However, a bottleneck in precursor production has limited the brightness of these luminescent plants. Here, we demonstrate the effectiveness of utilizing a computational model to guide a multiplex five-gene-silencing strategy by an artificial microRNA array to enhance caffeic acid and hispidin levels in plants. By combining loss-of-function-directed metabolic flux with a tyrosine-derived caffeic acid pathway, we achieved substantially enhanced bioluminescence levels. We successfully generated eFBP2 plants that emit considerably brighter bioluminescence for naked-eye reading by integrating all validated DNA modules. Our analysis revealed that the luminous energy conversion efficiency of the eFBP2 plants is currently very low, suggesting that luminescence intensity can be improved in future iterations. These findings highlight the potential to enhance plant luminescence through the integration of biological and information technologies.
ABSTRACT
Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap-a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed 'kinetic gene clusters' whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.
Subject(s)
RNA , Transcriptome , Humans , RNA/genetics , Kinetics , Gene Expression Profiling/methods , Gene Expression Regulation , Single-Cell Analysis/methodsABSTRACT
A nematic phase breaks the point-group symmetry of the crystal lattice and is known to emerge in correlated materials. Here we report the observation of an intra-unit-cell nematic order and associated Fermi surface deformation in the kagome metal ScV6Sn6. Using scanning tunnelling microscopy and scanning tunnelling spectroscopy, we reveal a stripe-like nematic order breaking the crystal rotational symmetry within the kagome lattice itself. Moreover, we identify a set of Van Hove singularities adhering to the kagome-layer electrons, which appear along one direction of the Brillouin zone and are annihilated along other high-symmetry directions, revealing rotational symmetry breaking. Via detailed spectroscopic maps, we further observe an elliptical deformation of the Fermi surface, which provides direct evidence for an electronically mediated nematic order. Our work not only bridges the gap between electronic nematicity and kagome physics but also sheds light on the potential mechanism for realizing symmetry-broken phases in correlated electron systems.
ABSTRACT
Spatial transcriptomic (ST) clustering employs spatial and transcription information to group spots spatially coherent and transcriptionally similar together into the same spatial domain. Graph convolution network (GCN) and graph attention network (GAT), fed with spatial coordinates derived adjacency and transcription profile derived feature matrix are often used to solve the problem. Our proposed method STGIC (spatial transcriptomic clustering with graph and image convolution) is designed for techniques with regular lattices on chips. It utilizes an adaptive graph convolution (AGC) to get high quality pseudo-labels and then resorts to dilated convolution framework (DCF) for virtual image converted from gene expression information and spatial coordinates of spots. The dilation rates and kernel sizes are set appropriately and updating of weight values in the kernels is made to be subject to the spatial distance from the position of corresponding elements to kernel centers so that feature extraction of each spot is better guided by spatial distance to neighbor spots. Self-supervision realized by Kullback-Leibler (KL) divergence, spatial continuity loss and cross entropy calculated among spots with high confidence pseudo-labels make up the training objective of DCF. STGIC attains state-of-the-art (SOTA) clustering performance on the benchmark dataset of 10x Visium human dorsolateral prefrontal cortex (DLPFC). Besides, it's capable of depicting fine structures of other tissues from other species as well as guiding the identification of marker genes. Also, STGIC is expandable to Stereo-seq data with high spatial resolution.
Subject(s)
Gene Expression Profiling , Transcriptome , Humans , Transcriptome/genetics , Benchmarking , Cluster Analysis , EntropyABSTRACT
Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties. This vaccine system could self-assemble into nanoparticles with uniform size (around 50 nm) and improve antigen accumulation as well as infiltration in the lymph node to increase antigen presentation. In vivo vaccination using this system conjugated with three predicted peptide neoantigen peptides from the MC38 tumor cell line induced 100% robust CD8+ T cell responses and superior tumor clearance compared to free peptides. This POx-based vaccine carrier represents a generalizable approach to increase the availability and efficacy of screened neoantigen peptides for a personalized cancer vaccine.
Subject(s)
Antigens, Neoplasm , Cancer Vaccines , Nanoparticles , Peptides , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Cancer Vaccines/chemistry , Peptides/chemistry , Peptides/immunology , Animals , Antigens, Neoplasm/immunology , Antigens, Neoplasm/chemistry , Mice , Nanoparticles/chemistry , Humans , Cell Line, Tumor , CD8-Positive T-Lymphocytes/immunology , Oxazoles/chemistry , Polymers/chemistry , Immunotherapy/methods , NanovaccinesABSTRACT
Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.
ABSTRACT
The control of spin relaxation mechanisms is of great importance for spintronics applications as well as for fundamental studies. Layered metal-halide perovskites represent an emerging class of semiconductors with rich optical spin physics, showing potential for spintronic applications. However, a major hurdle arises in layered metal-halide perovskites with strong spin-orbit coupling, where the spin lifetime becomes extremely short due to D'yakonov-Perel' scattering and Bir-Aronov-Pikus at high carrier density. Using the circularly polarized pump-probe transient reflection technique, we experimentally reveal the important scattering for spin relaxation beyond the electron-hole exchange strength in the Dion-Jacobson (DJ)-type 2D perovskites (3AMP)(MA)n-1PbnI3n+1 [3AMP = 3-(aminomethyl)piperidinium, n = 1-4]. Despite a more than 10-fold increase in carrier concentration, the spin lifetimes for n = 3 and 4 are effectively maintained. We reveal neutral impurity and polar optical phonon scatterings as significant contributors to the momentum relaxation rate. Furthermore, we show that more octahedral distortions induce a larger deformation potential which is reflected on the acoustic phonon properties. Coherent acoustic phonon analysis indicates that the polaronic effect is crucial in achieving control over the scattering mechanism and ensuring spin lifetime protection, highlighting the potential of DJ-phase perovskites for spintronic applications.
ABSTRACT
Under the control of chiral ligand glutathione and in the presence of hexadecyltrimethylammonium bromide, Au deposition on Au seeds is known to give chiral nanostructures. We have previously shown that the protruding chiral patterns, as opposed to flat facets, are likely caused by active surface growth, where nonuniform ligand coverage could be responsible for the focused growth at a few active sites. By pushing the limit of such a growth mode, here, we use decahedral seeds to prepare homochiral nanopropellers with intricate patterns of deep valleys and protruding ridges. Control experiments show that the focused growth depends on the rates of Au deposition by changing either the seed concentration or the reductant concentration, consistent with the proposed mechanism. The dynamic growth competition between the ligand-deficient active sites and the ligand-rich surfaces gradually focuses the growth onto a few active sites, causing the expansion of grooves, squeezing of steep ridges, and a surprising 36° rotation of the pentagonal outline. The imbalanced deposition on the prochiral slopes is responsible for the tilted grooves, the twisted walls, and thus the well-separated and distorted blades, which become the origin of the chiroptical responses.
ABSTRACT
Mesenchymal stem cells (MSCs) have emerged as an indispensable source for stem cell research and preclinical studies due to their capacity for in vitro proliferation and their potential to differentiate into mesodermal lineages, particularly into osteoblasts. This capability has propelled their application in the fields of bone regeneration and osteochondral repair. Traditional methodologies for assessing the differentiation status of MSCs necessitate invasive procedures such as cell lysis or fixation. In this study, we introduce a nondestructive technique that utilizes an integrated label-free approach to evaluate the osteogenic maturation of MSC spheroid aggregates. This method employs scanning electrochemical microscopy (SECM) with a flexible probe in conjunction with a top-removable microfluidic device designed for easy SECM access. By tracking the production rate of p-aminophenol (PAP) in the generation/collection mode and assessing morphological changes via the negative feedback mode using [Ru(NH3)6]Cl3 (Ruhex), we can discern variations in the alkaline phosphatase (ALP) activity indicative of osteogenic differentiation. This innovative strategy enables the direct evaluation of osteogenic differentiation in MSC spheroids cultured within microwell arrays without necessitating any labeling procedures. The utilization of a flexible microelectrode as the probe that scans in contact mode (with probe-substrate distances potentially as minimal as 0 µm) affords enhanced resolution compared to the traditional stiff-probe technique. Furthermore, this method is compatible with subsequent molecular biology assays, including gene expression analysis and immunofluorescence, thereby confirming the electrochemical findings and establishing the validity of this integrative approach.
Subject(s)
Cell Differentiation , Mesenchymal Stem Cells , Mesenchymal Stem Cells/cytology , Humans , Osteogenesis , Spheroids, Cellular/cytology , Alkaline Phosphatase/metabolism , Electrochemical Techniques , Aminophenols/chemistry , Microscopy/methods , Cells, Cultured , Microfluidic Analytical Techniques/instrumentationABSTRACT
Accurate lipid quantification is essential to revealing their roles in physiological and pathological processes. However, difficulties in the structural resolution of lipid isomers hinder their further accurate quantification. To address this challenge, we developed a novel stable-isotope N-Me aziridination strategy that enables simultaneous qualification and quantification of unsaturated lipid isomers. The one-step introduction of the 1-methylaziridine structure not only serves as an activating group for the CâC bond to facilitate positional identification but also as an isotopic inserter to achieve accurate relative quantification. The high performance of this reaction for the identification of unsaturated lipids was verified by large-scale resolution of the CâC positions of 468 lipids in serum. More importantly, by using this bifunctional duplex labeling method, various unsaturated lipids such as fatty acids, phospholipids, glycerides, and cholesterol ester were accurately and individually quantified at the CâC bond isomeric level during the mouse brain ischemia. This study provides a new approach to quantitative structural lipidomics.
Subject(s)
Fatty Acids , Lipidomics , Mice , Animals , Lipidomics/methods , Isomerism , Fatty Acids/chemistry , Phospholipids/chemistry , GlyceridesABSTRACT
Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. And several gene loci and transporter proteins that associated with uric acid transport functions have been identified. Retinol Dehydrogenase 12 (RDH12), recognized for its role in safeguarding photoreceptors, and our study investigated the potential impact of Rdh12 mutations on other organs and diseases, particularly hyperuricemia. We assessed Rdh12 mRNA expression levels in various tissues and conducted serum biochemical analyses in Rdh12-/- mice. Compared with the wild type, significant alterations in serum uric acid levels and kidney-related biochemical indicators have been revealed. Then further analysis, including quantitative RT-PCR of gene expression in the liver and kidney, highlighted variations in the expression levels of specific genes linked to hyperuricemia. And renal histology assessment exposed mild pathological lesions in the kidneys of Rdh12-/- mice. In summary, our study suggests that Rdh12 mutations impact not only retinal function but also contribute to hyperuricemia and renal disease phenotypes in mice. Our finding implies that individuals with Rdh12 mutations may be prone to hyperuricemia and gout, emphasizing the significance of preventive measures and regular examinations in daily life.
Subject(s)
Hyperuricemia , Mice , Animals , Hyperuricemia/genetics , Uric Acid , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , PhenotypeABSTRACT
Novel 2D materials with low-symmetry structures exhibit great potential applications in developing monolithic polarization-sensitive photodetectors with small volume. However, owing to the fact that at least half of them presented a small anisotropic factor of ≈2, comprehensive performance of present polarization-sensitive photodetectors based on 2D materials is still lower than the practical application requirements. Herein, a self-driven photodetector with high polarization sensitivity using a broken-gap ReSe2/SnSe2 van der Waals heterojunction (vdWH) is demonstrated. Anisotropic ratio of the photocurrent (Imax/Imin) could reach 12.26 (635 nm, 179 mW cm-2). Furthermore, after a facile combination of the ReSe2/SnSe2 device with multilayer graphene (MLG), Imax/Imin of the MLG/ReSe2/SnSe2 can be further increased up to13.27, which is 4 times more than that of pristine ReSe2 photodetector (3.1) and other 2D material photodetectors even at a bias voltage. Additionally, benefitting from the synergistic effect of unilateral depletion and photoinduced tunneling mechanism, the MLG/ReSe2/SnSe2 device exhibits a fast response speed (752/928 µs) and an ultrahigh light on/off ratio (105). More importantly, MLG/ReSe2/SnSe2 device exhibits excellent potential applications in polarized imaging and polarization-coded optical communication with quaternary logic state without any power supply. This work provides a novel feasible avenue for constructing next-generation smart polarization-sensitive photodetector with low energy consumption.
ABSTRACT
BACKGROUND: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. METHODS: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). RESULTS: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. CONCLUSIONS: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.
Subject(s)
Encephalitis , Humans , Prognosis , Child , Encephalitis/diagnosis , Encephalitis/microbiology , Encephalitis/virology , Encephalitis/drug therapy , Child, Preschool , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Male , Female , Metagenomics/methods , Infant , High-Throughput Nucleotide Sequencing , RNA/geneticsABSTRACT
Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.
Subject(s)
Cell Differentiation , Glycogen Synthase Kinase 3 beta , Mesenchymal Stem Cells , Osteogenesis , beta Catenin , Animals , Mice , beta Catenin/metabolism , Bone Marrow Cells/metabolism , Bone Marrow Cells/cytology , Glycogen Synthase Kinase 3 beta/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Signal TransductionABSTRACT
ConspectusNanosynthesis is the art of creating nanostructures, with on-demand synthesis as the ultimate goal. Noble metal nanoparticles have wide applications, but the available synthetic methods are still limited, often giving nanospheres and symmetrical nanocrystals. The fundamental reason is that the conventional weak ligands are too labile to influence the materials deposition, so the equivalent facets always grow equivalently. Considering that the ligands are the main synthetic handles in colloidal synthesis, our group has been exploring strong ligands for new growth modes, giving a variety of sophisticated nanostructures. The model studies often involve metal deposition on seeds functionalized with a certain strong ligand, so that the uneven distribution of the surface ligands could guide the subsequent deposition.In this Account, we focus on the design principles underlying the new growth modes, summarizing our efforts in this area along with relevant literature works. The basics of ligand control are first revisited. Then, the four major growth modes are summarized as follows: (1) The curvature effects would divert the materials deposition away from the high-curvature tips when the ligands are insufficient. With ligands fully covering the seeds, the sparser ligand packing at the tips would then promote the initial nucleation thereon. (2) The strong ligands may get trapped under the incoming metal layer, thus modulating the interfacial energy of the core-shell interface. The evidence for embedded ligands is discussed, along with examples of Janus nanostructures arising from the synthetic control, including metal-metal, metal-semiconductor, and metal-C60 systems using a variety of ligands. (3) Active surface growth is an unusual mode with divergent growth rates, so that part of the emerging surface is inhibited, and the growth is focused onto a few active sites. With seeds attached to oxide substrates, the selective deposition at the metal-substrate interface produces ultrathin nanowires. The synthesis can be generally applied to grow Au, Ag, Pd, Pt, and hybrid nanowires, with straight, spiral, or helical structures, and even rapid alteration of segments via electrochemical methods. In contrast, active surface growth for colloidal nanoparticles has to be more carefully controlled. The rich growth phenomena are discussed, highlighting the role of strong ligands, the control of deposition rates, the chiral induction, and the evidence for the active sites. (4) An active site with sparse ligands could also be exploited in etching, where the freshly exposed surface would promote further etching. The result is an unusual sharpening etching mode, in contrast to the conventional rounding mode for minimized surface energy.Colloidal nanosynthesis holds great promise for scalable on-demand synthesis, providing the crucial nanomaterials for future explorations. The strong ligands have delivered powerful synthetic controls, which could be further enhanced with in-depth studies on growth mechanisms and synthetic strategies, as well as functions and properties.