Imaging of Single Molecular Behaviors Under Bifurcated Three-Centered Hydrogen Bonding.

The mechanism for interaction and bonding of single guest molecules with active sites fundamentally determines the sorption and subsequent catalytic processes occurring in host zeolitic frameworks. However, no real-space studies on these significant issues have been reported thus far, since atomically visualizing guest molecules and recognizing single Al T-sites in zeolites remain challenging. Here, we atomically resolved single thiophene probes interacting with acid T-sites in the ZSM-5 framework to study the bonding behaviors between them. The synergy of bifurcated three-centered hydrogen bonds and van der Waals interactions can "freeze" the near-horizontal thiophene and make it stable enough to be imaged. By combining the imaging results with simulations, direct atomic observations enabled us to precisely locate the single Al T-sites in individual straight channels. Then, we statistically found that the thiophene bonding probability of the T11 site is 15 times higher than that of the T6 site. For different acid T-sites, the variation in the interaction synergy changes the inner angle of the host-guest O-H⋅⋅⋅S hydrogen bond, thereby affecting the stability of the near-horizontal thiophene and leading to considerable bonding inhomogeneities.

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.

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.

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.

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.

In situ imaging of the sorption-induced subcell topological flexibility of a rigid zeolite framework.

The crystallographic pore sizes of zeolites are substantially smaller than those inferred from catalytic transformation and molecular sieving capabilities, which reflects flexible variation in zeolite opening pores. Using in situ electron microscopy, we imaged the straight channels of ZSM-5 zeolite with benzene as a probe molecule and observed subcell flexibility of the framework. The opening pores stretched along the longest direction of confined benzene molecules with a maximum aspect change of 15%, and the Pnma space group symmetry of the MFI framework caused adjacent channels to deform. This compensation maintained the stability and rigidity of the overall unit cell within 0.5% deformation. The subcell flexibility originates mainly from the topologically soft silicon-oxygen-silicon hinges between rigid tetrahedral SiO4 units, with inner angles varying from 135° to 153°, as confirmed by ab initio molecular dynamics simulations.

Resolving atomic SAPO-34/18 intergrowth architectures for methanol conversion by identifying light atoms and bonds.

The micro-structures of catalyst materials basically affect their macro-architectures and catalytic performances. Atomically resolving the micro-structures of zeolite catalysts, which have been widely used in the methanol conversion, will bring us a deeper insight into their structure-property correlations. However, it is still challenging for the atomic imaging of silicoaluminophosphate zeolites by electron microscopy due to the limits of their electron beam sensitivity. Here, we achieve the real-space imaging of the atomic lattices in SAPO-34 and SAPO-18 zeolites, including the Al-O-P atoms and bonds, by the integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). The spatial distribution of SAPO-34 and SAPO-18 domains in SAPO-34/18 intergrowths can be clearly resolved. By changing the Si contents and templates in feed, we obtain two SAPO-34/18 catalysts, hierarchical and sandwich catalysts, with highly-mixed and separated SAPO-34 and SAPO-18 lattices respectively. The reduced diffusion distances of inside products greatly improve the catalytic performances of two catalysts in methanol conversion. Based on the observed distributions of lattices and elements in these catalysts, we can have a preliminary understanding on the correlation between the synthesis conditions and structures of SAPO-34/18 intergrowth catalysts to further modify their performances based on unique architectures.

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.

Intermittent theta burst stimulation (iTBS) combined with working memory training to improve cognitive function in schizophrenia: study protocol for a randomized controlled trial.

BACKGROUND: Working memory deficit is one of the most critical complex cognitive impairments in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy, but not still unsatisfactory. Intermittent theta burst stimulation (iTBS), which has recently been used in clinical practice, may have faster and stronger effects comparing the traditional model (10-Hz high-frequency rTMS). A large number of studies have showed that rTMS, especially iTBS, can enhance the neural plasticity of the brain, and cognitive training can improve the cognitive function of schizophrenia. Is there any facilitation effect of iTBS add on cognitive training (such as working memory training, WMT) on cognitive function enhancement in schizophrenia is still unknown. METHODS/DESIGN: The proposed study is designed of a double-center, double-blinded, randomized controlled trial that will include 200 schizophrenia patients between 18 and 45 years of age. The patients will be randomized to four groups, i.e., the study group (iTBS+WMT), WMS control group (iTBS+ Simple Response Training (SRT)), iTBS control group (sham iTBS+WMT), and placebo control (sham iTBS+SRT). The patients will receive 3 min 20 s of real or sham stimulation, followed by a short 1-2-min rest and 40 min of WMT training or SRT immediately. Neuropsychological and clinical symptom assessments, with functional and structural MRI, will be performed on baseline, post-treatment, and 3- and 6-month follow-up periods. The primary outcome is cognitive function measured by the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are changes in neuroplasticity, as measured by MRI and other behavioral assessments. DISCUSSION: The aim of our study is to explore the facilitation effects of iTBS added on WMT in improving cognitive function of schizophrenia. That means, patients with schizophrenia will benefit more in cognitive function improvement from the combination training mode of "preheating (iTBS stimulation changes the neural activity of working memory-related brain regions) and ironning (working memory training)." And the long-term effects of this combined training model will be assessed at a 6-month follow-up period. In case of a significant improvement of working memory with a prolonged effect, the iTBS combined with WMT protocol could be considered as a first-line clinical protocol in schizophrenia treatment. More broadly, the potential for increased universality and efficiency of rTMS with the iTBS model to enhance the neural plasticity of the brain should have a more positive effect on cognitive function in schizophrenia. TRIAL REGISTRATION: chictr.org.cn ChiCTR1900023405 . Registered on 25 May 2019.

Enhanced production of aromatics from propane with a temperature-shifting two-stage fluidized bed reactor.

A temperature-shifting two-stage fluidized bed reactor technology was used to convert propane and its intermediate products into aromatics. The first stage served for the aromatization of propane with a Ga/ZSM-5 catalyst at 570 °C. The second stage served for the alkylation of the intermediates of olefins at 300 °C. The increased yield of aromatics was attributed to the effective transformation of C2-C3 olefins as well as due to the suppression of the hydrogen transfer effect of the olefins.

RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein.

Mutations in cartilage oligomeric matrix protein (COMP), a large extracellular glycoprotein expressed in musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death and loss of growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor growth plate abnormalities, normal growth and longevity. This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias. We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA. A panel of shRNAs directed against COMP was tested. One shRNA (3B) reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels. The activity of the shRNA against COMP mRNA was maintained for up to 10 weeks. We also demonstrate that this treatment reduced ER stress. Moreover, we show that reducing steady state levels of COMP mRNA alleviates intracellular retention of other extracellular matrix proteins associated with the pseudoachondroplasia cellular pathology. These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.

An inducible cartilage oligomeric matrix protein mouse model recapitulates human pseudoachondroplasia phenotype.

Cartilage oligomeric matrix protein (COMP) is a pentameric extracellular protein expressed in cartilage and other musculoskeletal tissues. Mutations in the COMP gene cause pseudoachondroplasia (PSACH), a severe dwarfing condition that has a growth plate chondrocyte pathology. PSACH is characterized by intracellular retention of COMP and other extracellular matrix (ECM) proteins, which form an ordered matrix within large rough endoplasmic reticulum cisternae. This accumulation is cytotoxic and causes premature chondrocyte cell death, thereby depleting chondrocytes needed for normal long bone growth. Research to define the underlying molecular mechanisms of PSACH has been hampered by the lack of a suitable model system. In this study, we achieved robust expression of human mutant (MT) or wild-type (WT) COMP in mice by using a tetracycline-inducible promoter. Normal growth plate distribution of ECM proteins was observed in 1-month-old WT-COMP and C57BL\6 control mice. In contrast, the structure of the MT-COMP growth plate recapitulated the findings of human PSACH growth plate morphology, including (1) retention of ECM proteins, (2) intracellular matrix formation in the rER cisternae, and (3) increased chondrocyte apoptosis. Therefore, we have generated the first mouse model to show extensive intracellular retention of ECM proteins recapitulating the human PSACH disease process at the cellular level.