Elastic films of single-crystal two-dimensional covalent organic frameworks.

The properties of polycrystalline materials are often dominated by defects; two-dimensional (2D) crystals can even be divided and disrupted by a line defect1-3. However, 2D crystals are often required to be processed into films, which are inevitably polycrystalline and contain numerous grain boundaries, and therefore are brittle and fragile, hindering application in flexible electronics, optoelectronics and separation1-4. Moreover, similar to glass, wood and plastics, they suffer from trade-off effects between mechanical strength and toughness5,6. Here we report a method to produce highly strong, tough and elastic films of an emerging class of 2D crystals: 2D covalent organic frameworks (COFs) composed of single-crystal domains connected by an interwoven grain boundary on water surface using an aliphatic bi-amine as a sacrificial go-between. Films of two 2D COFs have been demonstrated, which show Young's moduli and breaking strengths of 56.7 ± 7.4 GPa and 73.4 ± 11.6 GPa, and 82.2 ± 9.1 N m-1 and 29.5 ± 7.2 N m-1, respectively. We predict that the sacrificial go-between guided synthesis method and the interwoven grain boundary will inspire grain boundary engineering of various polycrystalline materials, endowing them with new properties, enhancing their current applications and paving the way for new applications.

MRPS16 promotes lung adenocarcinoma growth via the PI3K/AKT/Frataxin signalling axis.

Although MRPS16 is involved in cancer development, its mechanisms in developing LAUD remain unclear. Herein, qRT-PCR, WB and IHC were utilized for evaluating MRPS16 expression levels, while functional assays besides animal experiments were performed to measure MRPS16 effect on LAUD progression. Using WB, the MRPS16 effect on PI3K/AKT/Frataxin signalling pathway was tested. According to our study, MRPS16 was upregulated in LAUD and was correlated to the advanced TNM stage as well as poor clinical outcomes, which represent an independent prognostic factor. Based on functional assays, MRPS16 is involved in promoting LAUD growth, migration and invasion, which was validated further in subsequent analyses through PI3K/AKT/Frataxin pathway activation. Moreover, MRPS16-knockdown-mediated Frataxin overexpression was shown to restore the reduction in tumour cells proliferation, migration and invasion. Our results revealed that MRPS16 caused an aggressive phenotype to LAUD and was a poor prognosticator; thus, targeting MRPS16 may be effectual in LAUD treatment.

Linker-Guided Growth of Single-Crystal Covalent Organic Frameworks.

The core features of covalent organic frameworks (COFs) are crystallinity and porosity. However, the synthesis of single-crystal COFs with monomers of diverse reactivity and adjustment of their pore structures remain challenging. Here, we show that linkers that can react with a node to form single-crystal COFs can guide other linkers that form either COFs or amorphous polymers with the node to gain single-crystal COFs with mixed components, which are homogeneous on the unit cell scale with controlled ratios. With the linker-guided crystal growth method, we created nine types of single-crystal COFs with up to nine different components, which are more complex than any known crystal. The structure of the crystal adapted approximately to that of the main component, and its pore volume could be expanded up to 8.8%. Different components lead to complex and diverse pore structures and offer the possibilities to gain positive synergies, as exemplified by a bicomponent COF with 2200 and 733% SO2 uptake capacity of that of the two pure-component counterparts at 298 K and 0.002 bar. The selectivity for separation of SO2/CO2 ranges from 1230 to 4247 for flue gas based on ideal adsorbed solution theory, recording porous crystals. The bicomponent COF also exhibits a 1300% retention time of its pure-component counterparts for SO2 in a dynamic column breakthrough experiment for deep desulfurization.

Growth and Local Structures of Single Crystalline Flakes of Three-Dimensional Covalent Organic Frameworks in Water.

Due to the enormous chemical and structural diversities and designable properties and functionalities, covalent organic frameworks (COFs) hold great promise as tailored materials for industrial applications in electronics, biology, and energy technologies. They were typically obtained as partially crystalline materials, although a few single-crystal three-dimensional (3D) COFs have been obtained recently with structures probed by diffraction techniques. However, it remains challenging to grow single-crystal COFs with controlled morphology and to elucidate the local structures of 3D COFs, imposing severe limitations on the applications and understanding of the local structure-property correlations. Herein, we develop a method for designed growth of five types of single crystalline flakes of 3D COFs with controlled morphology, front crystal facets, and defined edge structures as well as surface chemistry using surfactants that can be self-assembled into layered structures to confine crystal growth in water. The flakes enable direct observation of local structures including monomer units, pore structure, edge structure, grain boundary, and lattice distortion of 3D COFs as well as gradually curved surfaces in kinked but single crystalline 3D COFs with a resolution of up to ∼1.7 Å. In comparison with flakes of two-dimensional crystals, the synthesized flakes show much higher chemical, mechanical, and thermal stability.

Acteoside inhibits high glucose-induced oxidative stress injury in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.

Diabetes retinopathy (DR) is one of the most common microvascular complications of diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience a series of functional damages, which is an important factor in promoting the progression of DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but the mechanism of ACT in DR is not completely clear. Therefore, the purpose of the present study was to explore whether ACT inhibits the damage to RPE cells in a high glucose environment through antioxidative effects to alleviate the DR process. The DR in vitro cell model was constructed by treating RPE cells with high glucose, and the DR in vivo animal model was constructed by injecting streptozotocin (STZ) into the peritoneal cavity of mice to induce diabetes. The proliferation and apoptosis of RPE cells were detected by CCK-8 and flow cytometry assays, respectively. The expression changes in Nrf2, Keap1, NQO1 and HO-1 were evaluated by qRT‒PCR, Western blot and immunohistochemistry analyses. The MDA, SOD, GSH-Px and T-AOC contents were detected by kits. The changes in ROS and nuclear translocation of Nrf2 were observed by immunofluorescence assays. HE staining was used to measure the thickness of the outer nuclear layer (ONL) of the retina, and TUNEL staining was used to detect the number of apoptotic cells in the retinas of mice. In the present study, ACT effectively ameliorated outer retina damage in diabetic mice. In high glucose (HG)-induced RPE cells, ACT treatment had the following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted the nuclear translocation and expression of Nrf2, upregulated NQO1 and HO-1 (the target genes of Nrf2) expression, decreased ROS concentration, and increased the levels of the SOD, GSH-Px and T-AOC antioxidant indicators. However, knockdown of Nrf2 reversed the above phenomena, which indicated that the protective function of ACT in HG-induced RPE cells are closely related to Nrf2. In summary, the present study demonstrated that HG-induced oxidative stress injury is inhibited by ACT in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.

Oriented Growth of Thin Films of Covalent Organic Frameworks with Large Single-Crystalline Domains on the Water Surface.

It has been a longstanding challenge to rationally synthesize thin films of organic two-dimensional (2D) crystals with large single-crystalline domains. Here, we present a general strategy for the creation of 2D crystals of covalent organic frameworks (COFs) on the water surface, assisted by a charged polymer. The morphology of the preorganized monomers underneath the charged polymer on the water surface and their diffusion were crucial for the formation of the organic 2D crystals. Thin films of 2D COFs with an average single-crystalline domain size of around 3.57 ± 2.57 µm2 have been achieved, and their lattice structure, molecular structure, and grain boundaries were identified with a resolution down to 3 Å. The swing of chain segments and lattice distortion were revealed as key factors in compensating for the misorientation between adjacent grains and facilitating error corrections at the grain boundaries, giving rise to larger single-crystalline domains. The generality of the synthesis method was further proved with three additional 2D COFs. The oriented single-crystalline domains and clear grain boundaries render the films as model materials to study the dependence of the vertical conductivity of organic 2D crystals on domain sizes and chemical structures, and significant grain boundary effects were illustrated. This study presents a breakthrough in the controlled synthesis of organic 2D crystals with structural control at the molecular level. We envisage that this work will inspire further investigation into the microstructure-intrinsic property correlation of 2D COFs and boost their application in electronics.

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma.

PURPOSE: Glaucoma is a generic term of a highly different disease group of optic neuropathies, which the leading cause of irreversible vision in the world. There are few biomarkers available for clinical prediction and diagnosis, and the diagnosis of patients is mostly delayed. METHODS: Differential gene expression of transcriptome sequencing data (GSE9944 and GSE2378) for normal samples and glaucoma samples from the GEO database were analyzed. Furthermore, based on different algorithms (Logistic Regression (LR), Random Forest (RF), lasso regression (LASSO)) two diagnostic models are constructed and diagnostic markers are screened. GO and KEGG analyses revealed the possible mechanism of differential genes in the pathogenesis of glaucoma. ROC curve confirmed the effectiveness. RESULTS: LR-RF model included 3 key genes (NAMPT, ADH1C, ENO2), and the LASSO model outputted 5 genes (IFI16, RFTN1, NAMPT, ADH1C, and ENO2), both algorithms have excellent diagnostic efficiency. ROC curve confirmed that the three biomarkers ADH1C, ENO2, and NAMPT were effective in the diagnosis of glaucoma. Next, the expression analysis of the three diagnostic biomarkers in glaucoma and control samples confirmed that NAMPT and ADH1C were up-regulated in glaucoma samples, and ENO2 was down-regulated. Correlation analysis showed that ENO2 was significantly negatively correlated with ADH1C (cor = -0.865714202) and NAMPT (cor = -0.730541227). Finally, three compounds for the treatment of glaucoma were obtained in the TCMs database: acetylsalicylic acid, 7-o-methylisomucitol and scutellarin which were applied to molecular docking with the diagnostic biomarker ENO2. CONCLUSIONS: In conclusion, our research shows that ENO2, NAMPT, and ADH1C can be used as diagnostic markers for glaucoma, and ENO2 can be used as a therapeutic target.

MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a cause of poor prognosis in several lung diseases and after lung transplantation. In LIRI, matrix metalloproteinases and pyroptosis indicators change in parallel, both of them involvement of inflammatory modulation, but it is unclear whether they are related to each other. METHODS: We analyzed the matrix metalloproteinases (MMPs) changes from RNA sequencing (RNA-Seq) data of human transplantation and rat ischemia-reperfusion lung tissues in the Group on Earth Observations (GEO) database. Then established the mouse LIRI model to validate the changes. Further, the severity of lung injury was measured after intervening the matrix metalloproteinases changes with their selective inhibitor during Lung ischemia-reperfusion. Meanwhile, lung, pyroptosis was assessed by assaying the activity of Caspase-1 and interleukin 1ß (IL-1ß) before and after intervening the matrix metalloproteinases changes. RESULTS: The RNA-Seq data revealed that matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9) mRNA expression was elevated both in human lung transplantation and rat lung ischemia-reperfusion tissues, consistent with the change in our mouse model. At the same time, the activity of Caspase-1 and IL-1ß were increased after LIRI. While, the lung injury was attenuated for the use of MMP2 and MMP9 selective inhibitor SB-3CT. Likewise, lung pyroptosis alleviated when treatment the mice with SB-3CT in LIRI. CONCLUSION: We conclude that MMP2 and MMP9 are involved in the process of LIRI, the mechanism of which is related to the promotion of lung pyroptosis.

Double Lock Label Based on Thermosensitive Polymer Hydrogels for Information Camouflage and Multilevel Encryption.

Developing extra safety encryption technologies to prevent information leakage and combat fakes is in high demand but is challenging. Herein, we propose a "double lock" strategy based on both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) polymer hydrogels for information camouflage and multilevel encryption. Two types of hydrogels were synthesized by the method of random copolymerization. The number of -CO-NH2 groups in the network structure of the hydrogels changed the enthalpic or entropic thermo-responsive hydrogels, and ultimately precisely controlled their phase transition temperature. The crosslink density of the polymer hydrogels governs the diffusion kinetics, resulting in a difference in the time for their color change. The combination of multiple LCST and UCST hydrogels in one label realized information encryption and dynamic information identification in the dimensions of both time and temperature. This work is highly interesting for the fields of information encryption, anti-counterfeiting, and smart responsive materials.

Nanoporous and Highly Thermal Conductive Thin Film of Single-Crystal Covalent Organic Frameworks Ribbons.

Nanoporous materials are widely explored as efficient adsorbents for the storage of gases and liquids as well as for effective low-dielectric materials in large-scale integrated circuits. These applications require fast heat transfer, while most nanoporous substances are thermal insulators. Here, the oriented growth of micrometer-sized single-crystal covalent organic frameworks (COFs) ribbons with nanoporous structures at an air-water interface is presented. The obtained COFs ribbons are interconnected into a continuous and purely crystalline thin film. Due to the robust connectivity among the COFs ribbons, the entire film can be easily transferred and reliably contacted with target supports. The measured thermal conductivity amounts to ∼5.31 ± 0.37 W m-1 K-1 at 305 K, which is so far the highest value for nanoporous materials. These findings provide a methodology to grow and assemble single-crystal COFs into large area ensembles for the exploration of functional properties and potentially lead to new devices with COFs thin films where both porosity and thermal conductivity are desired.

Tungsten Oxide/Reduced Graphene Oxide Aerogel with Low-Content Platinum as High-Performance Electrocatalyst for Hydrogen Evolution Reaction.

Designing cost-effective, highly active, and durable platinum (Pt)-based electrocatalysts is a crucial endeavor in electrochemical hydrogen evolution reaction (HER). Herein, the low-content Pt (0.8 wt%)/tungsten oxide/reduced graphene oxide aerogel (LPWGA) electrocatalyst with excellent HER activity and durability is developed by employing a tungsten oxide/reduced graphene oxide aerogel (WGA) obtained from a facile solvothermal process as a support, followed by electrochemical deposition of Pt nanoparticles. The WGA support with abundant oxygen vacancies and hierarchical pores plays the roles of anchoring the Pt nanoparticles, supplying continuous mass transport and electron transfer channels, and modulating the surface electronic state of Pt, which endow the LPWGA with both high HER activity and durability. Even under a low loading of 0.81 µgPt cm-2 , the LPWGA exhibits a high HER activity with an overpotential of 42 mV at 10 mA cm-2 , an excellent stability under 10000-cycle cyclic voltammetry and 40 h chronopotentiometry at 10 mA cm-2 , a low Tafel slope (30 mV dec-1 ), and a high turnover frequency of 29.05 s-1 at η = 50 mV, which is much superior to the commercial Pt/C and the low-content Pt/reduced graphene oxide aerogel. This work provides a new strategy to design high-performance Pt-based electrocatalysts with greatly reduced use of Pt.

A Robust PtNi Nanoframe/N-Doped Graphene Aerogel Electrocatalyst with Both High Activity and Stability.

Insufficient catalytic activity and stability and high cost are the barriers for Pt-based electrocatalysts in wide practical applications. Herein, a hierarchically porous PtNi nanoframe/N-doped graphene aerogel (PtNiNF-NGA) electrocatalyst with outstanding performance toward methanol oxidation reaction (MOR) in acid electrolyte has been developed via facile tert-butanol-assisted structure reconfiguration. The ensemble of high-alloying-degree-modulated electronic structure and correspondingly the optimum MOR reaction pathway, the structure superiorities of hierarchical porosity, thin edges, Pt-rich corners, and the anchoring effect of the NGA, endow the PtNiNF-NGA with both prominent electrocatalytic activity and stability. The mass and specific activity (1647 mA mgPt -1 , 3.8 mA cm-2 ) of the PtNiNF-NGA are 5.8 and 7.8 times higher than those of commercial Pt/C. It exhibits exceptional stability under a 5-hour chronoamperometry test and 2200-cycle cyclic voltammetry scanning.

High-Performance Bismuth-Doped Nickel Aerogel Electrocatalyst for the Methanol Oxidation Reaction.

Low-cost, non-noble-metal electrocatalysts are required for direct methanol fuel cells, but their development has been hindered by limited activity, high onset potential, low conductivity, and poor durability. A surface electronic structure tuning strategy is presented, which involves doping of a foreign oxophilic post-transition metal onto transition metal aerogels to achieve a non-noble-metal aerogel Ni97 Bi3 with unprecedented electrocatalytic activity and durability in methanol oxidation. Trace amounts of Bi are atomically dispersed on the surface of the Ni97 Bi3 aerogel, which leads to an optimum shift of the d-band center of Ni, large compressive strain of Bi, and greatly increased conductivity of the aerogel. The electrocatalyst is endowed with abundant active sites, efficient electron and mass transfer, resistance to CO poisoning, and outstanding performance in methanol oxidation. This work sheds light on the design of high-performance non-noble-metal electrocatalysts.

Two-Dimensional Boronate Ester Covalent Organic Framework Thin Films with Large Single Crystalline Domains for a Neuromorphic Memory Device.

Despite the recent progress in the synthesis of crystalline boronate ester covalent organic frameworks (BECOFs) in powder and thin-film through solvothermal method and on-solid-surface synthesis, respectively, their applications in electronics, remain less explored due to the challenges in thin-film processability and device integration associated with the control of film thickness, layer orientation, stability and crystallinity. Moreover, although the crystalline domain sizes of the powder samples can reach micrometer scale (up to ≈1.5 µm), the reported thin-film samples have so far rather small crystalline domains up to 100 nm. Here we demonstrate a general and efficient synthesis of crystalline two-dimensional (2D) BECOF films composed of porphyrin macrocycles and phenyl or naphthyl linkers (named as 2D BECOF-PP or 2D BECOF-PN) by employing a surfactant-monolayer-assisted interfacial synthesis (SMAIS) on the water surface. The achieved 2D BECOF-PP is featured as free-standing thin film with large single-crystalline domains up to ≈60 µm2 and tunable thickness from 6 to 16 nm. A hybrid memory device composed of 2D BECOF-PP film on silicon nanowire-based field-effect transistor is demonstrated as a bio-inspired system to mimic neuronal synapses, displaying a learning-erasing-forgetting memory process.

Highly Crystalline and Semiconducting Imine-Based Two-Dimensional Polymers Enabled by Interfacial Synthesis.

Single-layer and multi-layer 2D polyimine films have been achieved through interfacial synthesis methods. However, it remains a great challenge to achieve the maximum degree of crystallinity in the 2D polyimines, which largely limits the long-range transport properties. Here we employ a surfactant-monolayer-assisted interfacial synthesis (SMAIS) method for the successful preparation of porphyrin and triazine containing polyimine-based 2D polymer (PI-2DP) films with square and hexagonal lattices, respectively. The synthetic PI-2DP films are featured with polycrystalline multilayers with tunable thickness from 6 to 200 nm and large crystalline domains (100-150 nm in size). Intrigued by high crystallinity and the presence of electroactive porphyrin moieties, the optoelectronic properties of PI-2DP are investigated by time-resolved terahertz spectroscopy. Typically, the porphyrin-based PI-2DP 1 film exhibits a p-type semiconductor behavior with a band gap of 1.38 eV and hole mobility as high as 0.01 cm2 V-1 s-1 , superior to the previously reported polyimine based materials.

Versatile Aerogels for Sensors.

Aerogels are unique solid-state materials composed of interconnected 3D solid networks and a large number of air-filled pores. They extend the structural characteristics as well as physicochemical properties of nanoscale building blocks to macroscale, and integrate typical characteristics of aerogels, such as high porosity, large surface area, and low density, with specific properties of the various constituents. These features endow aerogels with high sensitivity, high selectivity, and fast response and recovery for sensing materials in sensors such as gas sensors, biosensors and strain and pressure sensors, among others. Considerable research efforts in recent years have been devoted to the development of aerogel-based sensors and encouraging accomplishments have been achieved. Herein, groundbreaking advances in the preparation, classification, and physicochemical properties of aerogels and their sensing applications are presented. Moreover, the current challenges and some perspectives for the development of high-performance aerogel-based sensors are summarized.

HDAC3 modulates cancer immunity via increasing PD-L1 expression in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the second leading cause of cancer-related deaths worldwide. Despite immune checkpoints based immunotherapy highlights a new therapeutic strategy and achieves a remarkable therapeutic effect in various types of malignant tumors. Pancreatic cancer is one of the non-immunogenic cancers and is resistant to immunotherapy. Programmed death ligand 1 (PD-L1) is expressed on the surface of tumor cells and its level is a key determinant of the checkpoint immunotherapy efficacy. Here, we reported that the specific inhibitor of histone deacetylase 3 (HDAC3) decreased the protein and mRNA level of PD-L1 in pancreatic cancer cells. Furthermore, we showed that HDAC3 was critical for PD-L1 regulation and positively correlated with PD-L1 in PDAC patient specimens. Finally, we demonstrated that HDAC3/signal transducer and activator of transcription 3 (STAT3) pathway transcriptionally regulated PD-L1 expression. Collectively, our data contributes to a better understanding of the function of HDAC3 in cancer immunity and the regulatory mechanism of PD-L1. More importantly, these data suggest that the HDAC3 inhibitors might be used to improve immunotherapy in pancreatic cancer.

pH and Thermo Dual-Responsive Fluorescent Hydrogel Actuator.

As one of the most important smart materials, fluorescent hydrogel actuators can produce both color and shape changes under external stimuli. In the present work, an effective approach to develop a novel fluorescent hydrogel actuator with pH and thermo dual responsiveness is proposed. Through incorporating pH-responsive perylene tetracarboxylic acid (PTCA), which is a typical fluorescent moiety with aggregation-caused quenching (ACQ) effect, into an anisotropic poly(N-isopropylacrylamide)-polyacrylamide (PNIPAm-PAAm) structure, the obtained hydrogel exhibits stable thermoresponsive shape deformation and switchable fluorescence performance upon a pH trigger. Therefore, fluorescence-quenching-based and actuation-based information can be revealed when exposed to UV light and immersed into warm water, respectively. Moreover, the thermoresponsive actuating behavior can be applied to further hide the fluorescence-quenching-based images. The present work may provide new insights into the design and preparation of novel stimuli-responsive hydrogel actuators.

Soft-Template Construction of 3D Macroporous Polypyrrole Scaffolds.

A bottom-up approach toward 3D hierarchical macroporous polypyrrole aerogels is demonstrated via soft template-directed synthesis and self-assembly of ultrathin polypyrrole nanosheets in solution, which present interconnected macropores, ultrathin walls, and large specific surface areas, thereby exhibiting a high capacity, satisfactory rate capability, and excellent cycling stability for Na-ion storage.

Toward Activity Origin of Electrocatalytic Hydrogen Evolution Reaction on Carbon-Rich Crystalline Coordination Polymers.

The fundamental understanding of electrocatalytic active sites for hydrogen evolution reaction (HER) is significantly important for the development of metal complex involved carbon electrocatalysts with low kinetic barrier. Here, the MSx Ny (M = Fe, Co, and Ni, x/y are 2/2, 0/4, and 4/0, respectively) active centers are immobilized into ladder-type, highly crystalline coordination polymers as model carbon-rich electrocatalysts for H2 generation in acid solution. The electrocatalytic HER tests reveal that the coordination of metal, sulfur, and nitrogen synergistically facilitates the hydrogen ad-/desorption on MSx Ny catalysts, leading to enhanced HER kinetics. Toward the activity origin of MS2 N2 , the experimental and theoretical results disclose that the metal atoms are preferentially protonated and then the production of H2 is favored on the MN active sites after a heterocoupling step involving a N-bound proton and a metal-bound hydride. Moreover, the tuning of the metal centers in MS2 N2 leads to the HER performance in the order of FeS2 N2 > CoS2 N2 > NiS2 N2 . Thus, the understanding of the catalytic active sites provides strategies for the enhancement of the electrocatalytic activity by tailoring the ligands and metal centers to the desired function.