Atomic imaging of zeolite-confined single molecules by electron microscopy.

Single-molecule imaging with atomic resolution is a notable method to study various molecular behaviours and interactions1-5. Although low-dose electron microscopy has been proved effective in observing small molecules6-13, it has not yet helped us achieve an atomic understanding of the basic physics and chemistry of single molecules in porous materials, such as zeolites14-16. The configurations of small molecules interacting with acid sites determine the wide applications of zeolites in catalysis, adsorption, gas separation and energy storage17-21. Here we report the atomic imaging of single pyridine and thiophene confined in the channel of zeolite ZSM-5 (ref. 22). On the basis of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM)23-25, we directly observe the adsorption and desorption behaviours of pyridines in ZSM-5 under the in situ atmosphere. The adsorption configuration of single pyridine is atomically resolved and the S atoms in thiophenes are located after comparing imaging results with calculations. The strong interactions between molecules and acid sites can be visually studied in real-space images. This work provides a general strategy to directly observe these molecular structures and interactions in both the static image and the in situ experiment, expanding the applications of electron microscopy to the further study of various single-molecule behaviours with high resolution.

A single-molecule van der Waals compass.

Single-molecule imaging is challenging but highly beneficial for investigating intermolecular interactions at the molecular level1-6. Van der Waals interactions at the sub-nanometre scale strongly influence various molecular behaviours under confinement conditions7-11. Inspired by the traditional compass12, here we use a para-xylene molecule as a rotating pointer to detect the host-guest van der Waals interactions in the straight channel of the MFI-type zeolite framework. We use integrated differential phase contrast scanning transmission electron microscopy13-15 to achieve real-space imaging of a single para-xylene molecule in each channel. A good correlation between the orientation of the single-molecule pointer and the atomic structure of the channel is established by combining the results of calculations and imaging studies. The orientations of para-xylene help us to identify changes in the van der Waals interactions, which are related to the channel geometry in both spatial and temporal dimensions. This work not only provides a visible and sensitive means to investigate host-guest van der Waals interactions in porous materials at the molecular level, but also encourages the further study of other single-molecule behaviours using electron microscopy techniques.

Atomic Imaging of Multi-Dimensional Ruddlesden-Popper Interfaces in Lead-Halide Perovskites.

Ruddlesden-Popper (RP) interface with defined stacking structure will fundamentally influence the optoelectronic performances of lead-halide perovskite (LHP) materials and devices. However, it remains challenging to observe the atomic local structures in LHPs, especially for multi-dimensional RP interface hidden inside the nanocrystal. In this work, the advantages of two imaging modes in scanning transmission electron microscopy (STEM), including high-angle annular dark field (HAADF) and integrated differential phase contrast (iDPC) STEM, are successfully combined to study the bulk and local structures of inorganic and organic/inorganic hybrid LHP nanocrystals. Then, the multi-dimensional RP interfaces in these LHPs are atomically resolved with clear gap and blurred transition region, respectively. In particular, the complex interface by the RP stacking in 3D directions can be analyzed in 2D projected image. Finally, the phase transition, ion missing, and electronic structures related to this interface are investigated. These results provide real-space evidence for observing and analyzing atomic multi-dimensional RP interfaces, which may help to better understand the structure-property relation of LHPs, especially their complex local structures.

Interaction between Single Metal Atoms and UiO-66 Framework Revealed by Low-Dose Imaging.

Atomically dispersed metals encapsulated in metal-organic frameworks (MOFs) have attracted extensive attention in catalysis and energy fields. Amino groups were considered conducive to the formation of single atom catalysts (SACs) due to the strong metal-linker interactions. Here, atomic details of Pt1@UiO-66 and Pd1@UiO-66-NH2 are revealed using low-dose integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). Single Pt atoms locate on the benzene ring of p-benzenedicarboxylic acid (BDC) linkers in Pt@UiO-66, while single Pd atoms are adsorbed by the amino groups in Pd@UiO-66-NH2. However, Pt@UiO-66-NH2 and Pd@UiO-66 show obvious clusters. Therefore, amino groups do not always favor the formation of SACs, and density functional theory (DFT) calculations indicate that a moderate binding strength between metals and MOFs is preferred. These results directly reveal the adsorption sites of single metal atoms in UiO-66 family, paving the way for understanding the interaction between single metal atoms and the MOFs.

Binary Atomic Sites Enable a Confined Bidirectional Tandem Electrocatalytic Sulfur Conversion for Low-Temperature All-Solid-State Na-S Batteries.

The broader implementation of current all-solid-state Na-S batteries is still plagued by high operation temperature and inefficient sulfur utilization. And the uncontrollable sulfur speciation pathway along with the sluggish polysulfide redox kinetics further compromise the theoretical potentials of Na-S chemistry. Herein, we report a confined bidirectional tandem electrocatalysis effect to tune polysulfide electrochemistry in a novel low-temperature (80 °C) all-solid-state Na-S battery that utilizes Na3 Zr2 Si2 PO12 ceramic membrane as a platform. The bifunctional hollow sulfur matrix consisting binary atomically dispersed MnN4 and CoN4 hotspots was fabricated using a sacrificial template process. Upon discharge, CoN4 sites activate sulfur species and catalyze long-chain to short-chain polysulfides reduction, while MnN4 centers substantially accelerate the low-kinetic Na2 S4 to Na2 S directly conversion, manipulating the uniform deposition of electroactive Na2 S and avoiding the formation of irreversible products (e.g., Na2 S2 ). The intrinsic synergy of two catalytic centers benefits the Na2 S decomposition and minimizes its activation barrier during battery recharging and then efficiently mitigate the cathodic passivation. As a result, the stable cycling of all-solid-state Na-S cell delivers an attractive reversible capacity of 1060 mAh g-1 with a high CE of 98.5 % and a high energy of 1008 Wh kgcathode -1 , comparable to the liquid electrolyte cells.

Real-Space Imaging of the Node-Linker Coordination on the Interfaces between Self-Assembled Metal-Organic Frameworks.

Surface and interface, with unique local characteristics different from bulk structure, are of great significance in various applications of metal-organic frameworks (MOFs), which should be studied by real-space imaging methods, such as electron microscopy. However, it is still challenging to atomically resolve these local structures in MOFs, because they are even more sensitive to electron irradiation. Here, we use integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM) to achieve the atomic imaging of both the metal nodes and organic linkers in UiO-66 (Zr) nanocrystals and their assembly. After adding acetic acid, we modulate the whole process of MOF assembly and observe the organic linkers at both the surfaces and twin interfaces in the chemically assembled UiO-66 (Zr) crystals by the iDPC-STEM. These results bring us a deeper understanding on the role of acid modulators that promote the MOF assembly by generating the missing-linker defects on the crystal surface.

Systematic research of H2dedpa derivatives as potent inhibitors of New Delhi Metallo-ß-lactamase-1.

New Delhi Metallo-ß-lactamase-1 (NDM-1), a Zn (II)-dependent enzyme, can catalyze the hydrolysis of almost all ß-lactam antibiotics including carbapenems, resulting in bacterial antibiotic resistance, which threatens public health globally. Based on our finding that H2dedpa is as an efficient NDM-1 inhibitor, a series of H2dedpa derivatives was systematically prepared. These compounds exhibited significant activity against NDM-1, with IC50 values 0.06-0.94 µM. In vitro, compounds 6k and 6n could restore the activity of meropenem against Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis possessing either NDM or IMP. In particular, the activity of meropenem against E. coli producing NDM-4 could be improved up to 5333 times when these two compounds were used. Time-kill cell-based assays showed that 99.9% of P. mirabilis were killed when treated with meropenem in combination with compound 6k or 6n. Furthermore, compounds 6k and 6n were nonhemolytic (HC50 > 1280 µg/mL) and showed low toxicity toward mammalian (HeLa) cells. Mechanistic studies indicated that compounds 6k and 6n inhibit NDM-1 by chelating the Zn2+ ion of the enzyme.

Silicon Carbide as a Protective Layer to Stabilize Si-Based Anodes by Inhibiting Chemical Reactions.

Developing a practical silicon-based (Si-based) anode is a precondition for high-performance lithium-ion batteries. However, the chemical reactivity of the Si renders it liable to be consumed, which must be completely understood for it to be used in practical battery systems. Here, a fresh and fundamental mechanism is proposed for the rapid failure of Si-based materials. Silicon can chemically react with lithium hexafluorophosphate (LiPF6) to constantly generate lithium hexafluorosilicate (Li2SiF6) aggregates during cycling. In addition, nanocarbon coated on silicon acts as a catalyst to accelerate such detrimental reactions. By taking advantage of the high strength and toughness of silicon carbide (SiC), a SiC layer is introduced between the inner silicon and outer carbon layers to inhibit the formation of Li2SiF6. The side reaction rate decreases significantly due to the increase in the activation energy of the reaction. Si@SiC@C maintains a specific capacity of 980 mAh g-1 at a current density of 1 A g-1 after 800 cycles with an initial Coulombic efficiency over 88.5%. This study will contribute to improved design of Si-based anode for high-performance Li-ion batteries.

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig.

Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM) layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-ß1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT). The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-ß1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Electroacupuncture at Zusanli regulates the pathological phenotype of inflammatory bowel disease by modulating the NLRP3 inflammasome pathway.

BACKGROUND: This study sought to explore the effect of electroacupuncture (EA) intervention at Zusanli (ST36) acupoint on modulating the NLRP3 inflammasome pathway for treating inflammatory bowel disease (IBD). METHODS: C57BL/6 mice were administrated with 3% dextran sulfate sodium (DSS) to construct the IBD model. DSS mice were then administrated with EA (10 Hz, 1.5 mA) at ST36 for 7 days or intragastric administration of sulfasalazine (SASP) each day during the entire course. The control group animals were administered with distilled water. Then, partial least squares discriminant analysis revealed differences in the relative content of metabolites. The pathological changes of colon and spleen tissues were observed by H&E and immunohistochemistry (IHC) staining. qPCR determined the mRNA expression levels, while ELISA and western blot analysis determined the protein expression. RESULTS: Compared with the control groups, DSS-induced decreases of body weight were reversed after EA stimulation at ST36 or SASP treatment. The DAI of DSS mice was significantly higher relative to the control groups, whereas the DAI of DSS mice were decreased after EA stimulation at ST36 or SASP treatment. The intestinal weight/length ratio increased significantly in DSS groups; however, EA at ST36 significantly improved the macroscopic/microscopic characteristics and the weight and length of the colon. EA reversed inflammation and leukocyte infiltration and normalized the elevated levels of IL-1ß, IL-18, and NLRP3. Furthermore, EA improved the expression levels of ZO-1, occludin, and claudin 1, exhibiting normalization of the colon's tight junctions. CONCLUSIONS: EA at Zusanli acupoint of colon tissue significantly improved the pathological phenotype, showing a therapeutic effect on IBD.

Atomic Imaging of the Pb Precipitation in Lead-Halide Perovskites.

The lead iodide (PbI2 ) in lead-halide perovskite (LHP) is both a positive additive for material properties and a site for the formation of device defects. Therefore, atomic-level detection of PbI2 and its derived Pb structures are crucial for understanding the performance and stability of the LHP material. In this work, the atomic imaging of the LHP, PbI2 , and Pb lattices is achieved using low-dose integrated differential phase contrast (iDPC) scanning transmission electron microscopy (STEM). Combining it with the traditional high-angle annular dark field (HAADF)-STEM, the Pb precipitation in different LHPs (CsPbI3 , CsPbBr3, and FAPbI3 ) and under different conditions (light, air, and heat) can be investigated in real space. Then, the features of Pb precipitation (positions and sizes) are visually revealed under different conditions and the stabilities of different LHPs. Meanwhile, the pathway of Pb precipitation is directly imaged and confirmed by the iDPC-STEM during an in situ heating process, supporting the detailed mechanism of Pb precipitation. These results provide the visual evidence for analyzing atomic Pb precipitation in LHPs, which helps better understand the structure-property relation induced by Pb impurity.

Rationally Integrating Charge-Transfer Cocrystal and Ni(II) Organometallics for Visualized Photo/Thermochromic Sensors.

Smart materials demonstrate fascinating responses to environmental physical/chemical stimuli, including thermal, photonic, electronic, humidity, or magnetic stimuli, which have attracted intensive interest in material chemistry. However, their limited/harsh stimuli-responsive behavior or sophisticated postprocessing leads to enormous challenges for practical applications. Herein, we rationally designed and synthesized thermochromic Ni(II) organometallic [(C2H5)2NH2]2NiCl4-xBrx via a facile mechanochemical strategy, which demonstrated a reversible switch from yellow to blue color with a tunable phase-transition temperature from 75.6 to 61.7 °C. The simple electrospinning technology was applied to fabricate thermochromic Ni(II) organometallic-based nanofiber membranes for temperature monitoring. Furthermore, the organic charge-transfer cocrystal with a wide spectral absorption of 300-1950 nm and a high-efficiency photothermal conversion was combined with thermochromic Ni(II) organometallics for the desired dual-stimuli photo/thermochromism. This work supplies a new strategy for realizing multiple stimuli-responsive applications, such as thermal/light sensor displays and information storage.

Real-space imaging for discovering a rotated node structure in metal-organic framework.

Resolving the detailed structures of metal organic frameworks is of great significance for understanding their structure-property relation. Real-space imaging methods could exhibit superiority in revealing not only the local structure but also the bulk symmetry of these complex porous materials, compared to reciprocal-space diffraction methods, despite the technical challenges. Here we apply a low-dose imaging technique to clearly resolve the atomic structures of building units in a metal-organic framework, MIL-125. An unexpected node structure is discovered by directly imaging the rotation of Ti-O nodes, different from the unrotated structure predicted by previous X-ray diffraction. The imaged structure and symmetry can be confirmed by the structural simulations and energy calculations. Then, the distribution of node rotation from the edge to the center of a MIL-125 particle is revealed by the image analysis of Ti-O rotation. The related defects and surface terminations in MIL-125 are also investigated in the real-space images. These results not only unraveled the node symmetry in MIL-125 with atomic resolution but also inspired further studies on discovering more unpredicted structural changes in other porous materials by real-space imaging methods.

Benefits of Combining Sonchus brachyotus DC. Extracts and Synbiotics in Alleviating Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease, commonly abbreviated to NAFLD, is a pervasive ailment within the digestive system, exhibiting a rising prevalence, and impacting individuals at increasingly younger ages. Those afflicted by NAFLD face a heightened vulnerability to the onset of profound liver fibrosis, cardiovascular complications, and malignancies. Currently, NAFLD poses a significant threat to human health, and there is no approved therapeutic treatment for it. Recent studies have shown that synbiotics, which regulate intestinal microecology, can positively impact glucolipid metabolism, and improve NAFLD-related indicators. Sonchus brachyotus DC., a Chinese herb, exhibits hepatoprotective and potent antioxidant properties, suggesting its potential therapeutic use in NAFLD. Our preclinical animal model investigation suggests that the synergy between Sonchus brachyotus DC. extracts and synbiotics is significantly more effective in preventing and treating NAFLD, compared to the isolated use of either component. As a result, this combination holds the potential to introduce a fresh and encouraging therapeutic approach to addressing NAFLD.

Real-Space Imaging of the Molecular Changes in Metal-Organic Frameworks under Electron Irradiation.

Electron-induced structural changes influence the characterizations of the local structure of various materials by electron microscope. However, for beam-sensitive materials, it is still challenging to detect such changes by electron microscopy, which may help us quantitatively reveal how electrons interact with materials under electron irradiation. Here, we use an emergent phase contrast technique in electron microscopy to clearly image a metal-organic framework, UiO-66 (Zr), at an ultralow electron dose and dose rate. The effects of both the dose and dose rate on the UiO-66 (Zr) structure are visualized, which induce obvious missing organic linkers. The kinetics of the missing linker based on the radiolysis mechanism are semiquantitatively expressed by the different intensities of the imaged organic linkers. Deformation of the UiO-66 (Zr) lattice after the missing linker is also observed. These observations make it possible to visually investigate the electron-induced chemistry in various beam-sensitive materials and avoid electron damage to them.

Atomically Unraveling the Structural Evolution of Surfaces and Interfaces in Metal Halide Perovskite Quantum Dots.

Revealing the local structural change of metal halide perovskites (MHPs) induced by external conditions is important to understand its performance and stability in optoelectronic applications. However, previous studies on the properties and structures of MHPs are usually limited by the spatial resolution of the probe, and it is still challenging to obtain its atomic structural information in real space. In this work, the integrated differential-phase-contrast scanning transmission electron microscopy is applied to the low-dose imaging of CsPbI3 quantum dots (QDs). In particular, the local structures in QDs, such as surfaces and interfaces, can be atomically resolved. Then, the structural evolution of CsPbI3 QDs under various external conditions can be unraveled during in situ heating or ex situ treatments, where it lose cubic shapes and fuse to larger particles. The changes in surfaces and interfaces with missing Cs ions and PbI6 octahedrons can be semi-quantitatively studied by profile analysis and bond-length measurement in images. Finally, density functional theory calculations are performed to illustrate the properties and stabilities of the different structures that are observed. These results provide atomic-scale insights into the structural evolution of QDs, which is of great importance to modify the performance of perovskite materials and devices.

In situ imaging of the atomic phase transition dynamics in metal halide perovskites.

Phase transition dynamics are an important concern in the wide applications of metal halide perovskites, which fundamentally determine the optoelectronic properties and stabilities of perovskite materials and devices. However, a more in-depth understanding of such a phase transition process with real atomic resolution is still limited by the immature low-dose electron microscopy and in situ imaging studies to date. Here, we apply an emergent low-dose imaging technique to identify different phase structures (α, ß and γ) in CsPbI3 nanocrystals during an in-situ heating process. The rotation angles of PbI6 octahedrons can be measured in these images to quantitatively describe the thermal-induced phase distribution and phase transition. Then, the dynamics of such a phase transition are studied at a macro time scale by continuously imaging the phase distribution in a single nanocrystal. The structural evolution process of CsPbI3 nanocrystals at the particle level, including the changes in morphology and composition, is also visualized with increasing temperature. These results provide atomic insights into the transition dynamics of perovskite phases, indicating a long-time transition process with obvious intermediate states and spatial distribution that should be generally considered in the further study of structure-property relations and device performance.

Development of Aromatic-Linked Diamino Acid Antimicrobial Peptide Mimics with Low Hemolytic Toxicity and Excellent Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become one of the biggest threats to public health. To develop new antibacterial agents against MRSA, a series of diamino acid compounds with aromatic nuclei linkers were designed and synthesized. Compound 8j, which exhibited low hemolytic toxicity and the best selectivity against S. aureus (SI > 2000), showed good activity against clinical MRSA isolates (MIC = 0.5-2 µg/mL). Compound 8j was able to quickly kill bacteria without inducing bacterial resistance. A mechanistic study and transcriptome analysis revealed that compound 8j can act on phosphatidylglycerol and induce the accumulation of endogenous reactive oxygen species, which can destroy bacterial membranes. Importantly, compound 8j achieved a 2.75 log reduction of MRSA count at 10 mg/kg/d in a mouse subcutaneous infection model. These findings suggested that compound 8j had the potential to be an antibacterial agent against MRSA.

Synbiotics and Gut Microbiota: New Perspectives in the Treatment of Type 2 Diabetes Mellitus.

The number of people with type 2 diabetes mellitus (T2DM) has increased sharply over the past decades. Apart from genetic predisposition, which may cause some of the diagnosed cases, an unhealthy diet and lifestyle are incentive triggers of this global epidemic. Consumption of probiotics and prebiotics to gain health benefits has become increasingly accepted by the public in recent years, and their critical roles in alleviating T2DM symptoms are confirmed by accumulating studies. Microbiome research reveals gut colonization by probiotics and their impacts on the host, while oral intake of prebiotics may stimulate existing metabolisms in the colon. The use of synbiotics (a combination of prebiotics and probiotics) can thus show a synergistic effect on T2DM through modulating the gastrointestinal microenvironment. This review summarizes the research progress in the treatment of T2DM from the perspective of synbiotics and gut microbiota and provides a class of synbiotics which are composed of lactulose, arabinose, and Lactobacillus plantarum, and can effectively adjust the blood glucose, blood lipid, and body weight of T2DM patients to ideal levels.

Modulating inherent lewis acidity at the intergrowth interface of mortise-tenon zeolite catalyst.

The acid sites of zeolite are important local structures to control the products in the chemical conversion. However, it remains a great challenge to precisely design the structures of acid sites, since there are still lack the controllable methods to generate and identify them with a high resolution. Here, we use the lattice mismatch of the intergrown zeolite to enrich the inherent Lewis acid sites (LASs) at the interface of a mortise-tenon ZSM-5 catalyst (ZSM-5-MT) with a 90° intergrowth structure. ZSM-5-MT is formed by two perpendicular blocks that are atomically resolved by integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). It can be revealed by various methods that novel framework-associated Al (AlFR) LASs are generated in ZSM-5-MT. Combining the iDPC-STEM results with other characterizations, we demonstrate that the partial missing of O atoms at interfaces results in the formation of inherent AlFR LASs in ZSM-5-MT. As a result, the ZSM-5-MT catalyst shows a higher selectivity of propylene and butene than the single-crystal ZSM-5 in the steady conversion of methanol. These results provide an efficient strategy to design the Lewis acidity in zeolite catalysts for tailored functions via interface engineering.