Unit-cell-thick zeolitic imidazolate framework films for membrane application.

Zeolitic imidazolate frameworks (ZIFs) are a subset of metal-organic frameworks with more than 200 characterized crystalline and amorphous networks made of divalent transition metal centres (for example, Zn2+ and Co2+) linked by imidazolate linkers. ZIF thin films have been intensively pursued, motivated by the desire to prepare membranes for selective gas and liquid separations. To achieve membranes with high throughput, as in ångström-scale biological channels with nanometre-scale path lengths, ZIF films with the minimum possible thickness-down to just one unit cell-are highly desired. However, the state-of-the-art methods yield membranes where ZIF films have thickness exceeding 50 nm. Here we report a crystallization method from ultradilute precursor mixtures, which exploits registry with the underlying crystalline substrate, yielding (within minutes) crystalline ZIF films with thickness down to that of a single structural building unit (2 nm). The film crystallized on graphene has a rigid aperture made of a six-membered zinc imidazolate coordination ring, enabling high-permselective H2 separation performance. The method reported here will probably accelerate the development of two-dimensional metal-organic framework films for efficient membrane separation.

Pseudorabies virus kinase UL13 phosphorylates H2AX to foster viral replication.

The DNA damage response (DDR) pathway is critical for maintaining genomic integrity and sustaining organismal development. Viruses can either utilize or circumvent the DDR to facilitate their replication. Pseudorabies virus (PRV) infection was shown to induce apoptosis via stimulating DDR. However, the underlying mechanisms have not been fully explored to date. This study showed that PRV infection robustly activates the ATM and DNA-PK signaling pathways shortly after infection. However, inhibition of ATM, but not DNA-PK, could dampen PRV replication in cells. Importantly, we found that PRV-encoded serine/threonine kinase UL13 interacts with and subsequently phosphorylates H2AX. Furthermore, we found that UL13 deletion largely attenuates PRV neuroinvasiveness and virulence in vivo. In addtion, we showed that UL13 contributes to H2AX phosphorylation upon PRV infection both in vitro and in vivo, but does not affect ATM phosphorylation. Finally, we showed that knockdown of H2AX reduces PRV replication, while this reduction can be further enhanced by deletion of UL13. Taken together, we conclude that PRV-encoded kinase UL13 regulates DNA damage marker γH2AX and UL13-mediated H2AX phosphorylation plays a pivotal role in efficient PRV replication and progeny production.

Mechanochemistry of Metal-Organic Frameworks under Pressure and Shock.

ConspectusMetal-organic framework solids (MOFs) are synthetic nanoporous materials that have drawn intense efforts in synthesis and characterization of chemical properties, most notably for their ability to adsorb liquids and gases. They are constructed as "node-spacer" nanostructured materials: metal centers (ions or clusters) connected by organic linkers (commonly containing carboxylate or imidazolate groups) to form crystalline, extended, often highly nanoporous structures. MOFs exhibit a variety of advantages over conventional porous materials: rationally designed synthesis of desired crystal structures and crystal engineering become feasible; great synthetic versatility and ease of incorporating different chemical functionalities are realized; and the use of lightweight organic linkers allows for ultrahigh surface area and porosity previously not accessible to conventional materials (i.e., zeolites and porous carbon). As a consequence, MOFs show great promise for a rapidly expanding collection of applications such as gas storage, separations, catalysis, sensing, and drug delivery.The mechanochemistry of MOFs and their response to shock waves, which we discuss in this Account, have been only partially explored. Mechanochemistry, the connection between the mechanical and the chemical worlds, has ancient origins. Rubbing sticks together to start a fire is mechanochemistry. Only in the past decade or so, however, has mechanochemistry gained a notable focus in the chemical community. In the following discussion, we present a general introduction to the complex mechanochemical behavior of MOFs both under quasi-static compression and under shock loading created by high-speed impact. During elastic deformation, MOFs undergo reversible structural or phase transitions. Plastic deformation of MOFs can result in mechanochemistry and can permanently modify the crystal structure, the pore dimensions and configuration, and the chemical bonding. The large energies required to induce bond rearrangement during plastic deformation suggest an interesting potential of MOFs for shock wave mitigation applications.MOFs are promising materials for shock energy dissipation because of the high density of nanopores which can absorb shock energy as they collapse. We have recently developed a platform to assess shock wave energy attenuation by MOFs and other powdered materials. It uses a tabletop laser-driven flyer plate to impact MOF samples at velocities of up to 2.0 km/s. The pressure of the shock waves that break out from the MOF sample can be measured by photon Doppler velocimetry. By measuring the shock profiles of MOF layers with different thicknesses, we can determine the shock pressure attenuation by the MOF layer. We have identified the two-wave structure of shocks in MOFs caused by nanopore collapse. Electron micrographs of recovered shocked MOFs show distinct zones in the shocked material corresponding to shock powder compaction, nanopore collapse, and chemical bond destruction.

PRV UL13 inhibits cGAS-STING-mediated IFN-ß production by phosphorylating IRF3.

Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky's disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-ß production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-ß secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS-STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS-STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-ß gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS-STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-ß gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS-STING-mediated IFN-ß production by phosphorylating IRF3.

Shock Wave Energy Absorption in Metal-Organic Framework.

Recent investigations into the mechanical properties and mechanochemical reactions of metal-organic frameworks (MOFs) have suggested the potential for energy dissipation by multiple mechanisms. Although the possibility of efficient multifunctional shock dissipation by MOFs was suggested by static high pressure studies, there is little known about MOFs under shock compression. Here, we measure the attenuation of shock wave by the MOF denoted zeolitic-imidazolate framework (ZIF-8) in its desolvated, porous state. We find that shock wave dissipation by ZIF-8 occurred by multiple processes: powder compaction, nanopore-collapse, and chemical bond-breakage. The shock energy absorbance in ZIF-8 is proportional to ZIF-8 thickness, allowing the prediction of the thickness of MOF layer needed to attenuate shock waves to a desired lower energy. Compared with PMMA, often used as a standard, ZIF-8 attenuates 7 times more shock energy per unit mass for impacts at a lower velocity of 0.75 km/s and 2.5 times more at a higher velocity of 1.6 km/s. This research illustrates how to improve the ability to attenuate shock waves for personnel and equipment protection by engineering multifunctionality into the shock wave absorbing armor material.

Energy Storage during Compression of Metal-Organic Frameworks.

Practical applications of metal-organic framework (MOF) materials require an in-depth understanding of their mechanical properties. We have investigated the mechanical properties and energy absorption behavior of single crystals of four isostructural UiO-type MOFs under uniaxial compression. In situ nanocompression experiments were used to measure the mechanical behavior of individual MOF nanocrystals under compression within a transmission electron microscope. The plasticity and endothermicity during deformation of MOFs shows a surprising potential for absorption and dissipation of mechanical shock. At compressive stress below 2 GPa, relatively small amounts of energy (<0.3 kJ/g) are absorbed by the compression of these MOFs. As the stress was increased, however, the energy absorption was significantly enhanced. Above 2 GPa, the energy absorption typically reaches 3-4 kJ/g; for comparison, the energy release in the explosion of TNT is ∼4 kJ/g. Gram for gram, MOFs can absorb as much energy as a high explosive can release.

Shock Wave Chemistry in a Metal-Organic Framework.

Metal-organic frameworks (MOFs) have potential applications as energy absorbing materials for shock wave energy mitigation due to their nanoporosity. Here we have examined km/s laser-driven flyer plate impacts on a prototypical MOF, ZIF-8. We observed particle fragmentation and morphological changes in microcrystals of ZIF-8 at lower shock pressures (≈2.5 GPa), and amorphization and structural collapse at higher pressures (≈8 GPa). High-speed emission spectroscopy revealed that 50 ns after flyer plate impacts, an emission pulse was generated by ZIF-8 resulting from chemical bonds that were broken and subsequently reformed. MOFs may prove useful in the dissipation of shock wave energy through large structural changes (free volume collapse and endothermic bond breakage).

Impact of Shape Persistence on the Porosity of Molecular Cages.

Porous materials provide a plethora of technologically important applications that encompass molecular separations, catalysis, and adsorption. The majority of research in this field involves network solids constructed from multitopic constituents that, when assembled either covalently or ionically, afford macromolecular arrangements with micro- or meso-porous apertures. Recently, porous solids fabricated from discrete organic cages have garnered much interest due to their ease of handling and solution processability. Although this class of materials is a promising alternative to network solids, fundamental studies are still required to elucidate critical structure-function relationships that govern microporosity. Here, we report a systematic investigation of the effects of building block shape-persistence on the porosity of molecular cages. Alkyne metathesis and edge-specific postsynthetic modifications afforded three organic cages with alkynyl, alkenyl, and alkyl edges, respectively. Nitrogen adsorption experiments conducted on rapidly crystallized and slowly crystallized solids illustrated a general trend in porosity: alkynyl > alkenyl > alkyl. To understand the molecular-scale origin of this trend, we investigated the short and long time scale molecular motions of the molecular cages using ab initio molecular dynamics (AIMD) and classical molecular dynamics (MD) simulations. Our combined experimental and computational results demonstrate that the microporosity of molecular cages directly correlates with shape persistence. These findings discern fundamental molecular requirements for rationally designing porous molecular solids.

Compression-induced deformation of individual metal-organic framework microcrystals.

The deformation and mechanical behavior of individual zeolitic-imidazolate framework (ZIF-8) micro- and sub-microcrystals were observed under compression. Young's modulus and volume changes as a function of applied pressure were determined on individual single crystals, offering insights in the relationship among structure, morphology, and mechanical properties. Dramatic volume decreases and amorphization were detected during compression over a pressure range of 0-4 GPa for individual 1.2 µm ZIF-8 microcrystals, and the deformed microcrystals partially recovered after pressure release. The orientation and size effects on the mechanical behavior of ZIF-8 nano- and microcrystals were also investigated. The presence of solvates within the pores of the ZIF-8 has a dramatic effect on the mechanical properties of the single crystals. Methanol-solvated ZIF-8 microcrystals are much less deformable than the desolvated microcrystals and shatter completely at very low applied force.

Tetrandrine (TET) inhibits African swine fever virus entry into cells by blocking the PI3K/Akt pathway.

African Swine Fever Virus (ASFV) infection causes an acute and highly contagious disease in swine, resulting in significant economic losses and societal harm worldwide. Currently, there are no effective vaccines or antiviral drugs available for ASFV. Tetrandrine (TET) is extracted from the traditional Chinese herb Stephania tetrandrae, possesses diverse biological functions such as anti-inflammatory, anti-tumor, and antiviral activities. The study comprehensively evaluated the anti-ASFV effect of TET and validated it through biological assays. The dose-dependent inhibition of TET against ASFV was confirmed and a novel mechanism of TET's anti-ASFV activity was elucidated. TET effectively inhibits ASFV during internalization by blocking macropinocytosis through the inhibition of the PI3K/Akt pathway. The specific inhibitor LY294002, targeting the PI3K/Akt pathway, exhibits similar antiviral activity against ASFV as TET. Furthermore, the inhibitory effect of TET against other viruses such as Lumpy Skin Disease Virus (LSDV) and Porcine Epidemic Diarrhea Virus (PEDV) was also identified. Our findings suggest that TET effectively inhibits ASFV and reveal the potential for broad-spectrum antiviral drugs targeting the PI3K/Akt pathway.

In Situ Tracking of Nonthermal Plasma Etching of ZIF-8 Films.

Surface characterization is critical for understanding the processes used for preparing catalysts, sorbents, and membranes. Nonthermal plasma (NTP) is a process that achieves high reactivity at low temperatures and is used to tailor the surface properties of materials. In this work, we combine the capabilities of infrared reflection absorption spectroscopy (IRRAS) with NTP for the in situ interrogation of zeolitic imidazolate framework-8 (ZIF-8) thin films to probe modifications in the material induced by oxygen and nitrogen plasmas. The IRRAS measurements in oxygen plasma reveal etching of organic ligands with sequential removal of the methyl group and imidazole ring and with the formation of carbonyl moieties (C═O). In contrast, nitrogen plasma induces mild etching and grafting of nitrile groups (-C≡N). Scanning electron microscopy imaging shows that oxygen plasma, at prolonged times, significantly degrades the ZIF-8 film at the grain boundaries. Treatment of ZIF-8 membranes using mild plasma conditions yields a fivefold enhancement for H2/N2 and CO2/CH4 ideal selectivities and an eightfold enhancement for CO2/N2 ideal selectivity. Additionally, the new tools described here can be used for spectroscopic in situ tracking of plasma-induced chemistry on thin films in general.

Solvent-free bottom-up patterning of zeolitic imidazolate frameworks.

Patterning metal-organic frameworks (MOFs) at submicrometer scale is a crucial yet challenging task for their integration in miniaturized devices. Here we report an electron beam (e-beam) assisted, bottom-up approach for patterning of two MOFs, zeolitic imidazolate frameworks (ZIF), ZIF-8 and ZIF-67. A mild pretreatment of metal oxide precursors with linker vapor leads to the sensitization of the oxide surface to e-beam irradiation, effectively inhibiting subsequent conversion of the oxide to ZIFs in irradiated areas, while ZIF growth in non-irradiated areas is not affected. Well-resolved patterns with features down to the scale of 100 nm can be achieved. This developer-free, all-vapor phase technique will facilitate the incorporation of MOFs in micro- and nanofabrication processes.

Structural insight into African swine fever virus I73R protein reveals it as a Z-DNA binding protein.

African Swine Fever (ASF) is a highly contagious viral haemorrhagic disease of swine, leading to enormous economic losses in the swine industry. However, vaccines and drugs to treat ASF have yet to be developed. African swine fever virus (ASFV) encodes more than 150 proteins, but 50% of them have unknown functions. Here, we present the crystal structure of the ASFV I73R protein at a resolution of 2.0 Å. Similar search tools based solely on amino acid sequence shows that it has no relationships to any proteins of known function. Interestingly, the overall structure of the I73R protein shares a winged helix-turn-helix fold, structural similarity with the Z-DNA binding domain (Zα). In accordance with this result, the I73R is capable of binding to a CpG repeats DNA duplex, which has a high propensity for forming Z-DNA during the DNA binding assays. In addition, the I73R protein was shown to be expressed at both early and late stages of ASFV post-infection in PAM cells as an 8.9 kDa protein. Immunofluorescence studies revealed that the I73R protein is expressed in the nucleus at early times post-infection and gradually translocated from the nucleus to the cytoplasm. Taken together, these data indicate that the I73R could be a member of Zα family that is important in host-pathogen interaction, which paves the way for the design of inhibitors to target this severe pathogen. Further exploring the biological role of I73R during ASFV infection in vitro and in vivo will provide new clues for development of new antiviral strategies.

Emergence of a novel pathogenic recombinant virus from Bartha vaccine and variant pseudorabies virus in China.

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, has resulted in substantial economic losses in the swine industry worldwide. Previous reports have shown that the PRV variant is responsible for the Pseudorabies outbreaks in Bartha-K61-vaccinated farms in China. However, there is limited information about the evolution of recombination of the PRV variant. Here, we isolated two PRV variants from a Bartha-K61-vaccinated swine farm, named them the JSY7 and JYS13 strains, analysed their complete genomic sequences and evaluated pathogenicity. As results, the JSY7 and JSY13 strains showed different cytopathic effects and plaque sizes. The JSY7 and JSY13 strains had the same Aspartate insertions in the gE protein as other PRV variants. The JSY7 and JSY13 strains were clustered into the same clade based on a genomic phylogenetic analysis. However, the JSY7 strain was relatively close to recent PRV isolates in China, while the JSY13 strain was more closely related to earlier PRV isolates. Interestingly, the gC gene phylogenetic tree showed that the JSY7 strain belonged to genotype II lineage 3, while the JSY13 strain belonged to genotype I and is the same branch with the Bartha strain. Furthermore, the PRV variants were relatively distant from the Bartha strain in the phylogenetic analysis of the gB, gC and gD genes. Importantly, a recombination analysis showed that the JSY13 strain might be a natural recombinant between the minor parental genotype I Bartha strain and the major parental genotype II JSY7 strain. Finally, we also found that the JSY13 strain showed a moderate virulence compared to the JSY7 strain in mice. Taken together, our data provide direct evidence for genomic recombination of PRV in nature, which may play an important role in the evolution and virulence of PRV. This discovery suggests that live PRV vaccine can act as genetic donors for genomic recombination.

Electron beam induced modification of ZIF-8 membrane permeation properties.

Modification of the gas permeation properties of ZIF-8 membranes using electron beam irradiation is reported. 3.8 and 3.2 fold enhancements in ideal selectivity for CO2/N2 and CO2/CH4 can be achieved with less than 1 min exposure time.

High energy flexible supercapacitors formed via bottom-up infilling of gel electrolytes into thick porous electrodes.

Formation of thick, high energy density, flexible solid supercapacitors is challenging because of difficulties infilling gel electrolytes into porous electrodes. Incomplete infilling results in a low capacitance and poor mechanical properties. Here we report a bottom-up infilling method to overcome these challenges. Electrodes up to 500 µm thick, formed from multi-walled carbon nanotubes and a composite of poly(3,4-ethylenedioxythiophene), polystyrene sulfonate and multi-walled carbon nanotubes are successfully infilled with a polyvinyl alcohol/phosphoric acid gel electrolyte. The exceptional mechanical properties of the multi-walled carbon nanotube-based electrode enable it to be rolled into a radius of curvature as small as 0.5 mm without cracking and retain 95% of its initial capacitance after 5000 bending cycles. The areal capacitance of our 500 µm thick poly(3,4-ethylenedioxythiophene), polystyrene sulfonate, multi-walled carbon nanotube-based flexible solid supercapacitor is 2662 mF cm-2 at 2 mV s-1, at least five times greater than current flexible supercapacitors.

Bond breakage under pressure in a metal organic framework.

The internal free volume of porous materials diminishes upon mechanical compression, and such volume collapse can have chemical consequences. We report here the endothermic bond breakage in a metal-organic framework (MOF) during compression-induced collapse. Upon bulk compression at 1.9 GPa, the effective number for Zr-O bonds between Zr(iv) ions and carboxylate groups in UiO-66 decreased from 4.0 to 1.9, as determined by EXAFS, and the internal free volume was synchronously collapsed. Consistent with the EXAFS data, IR spectra confirmed conversion of syn-syn bridging carboxylates to monodentate ligation, thus establishing mechanochemical reactions induced by external compression of MOFs. Substantial mechanical energy (∼4 kJ g-1) was absorbed by UiO-66 nanocrystals during compression, as demonstrated from nanocompression of single crystals (600 nm) in situ during scanning electron microscopy, which establishes the potential application of MOFs as mechanical energy absorbers for hydrostatic and shock compression.

Age-related changes of corneal endothelial cell in healthy Chinese tree shrew measured by non-contact specular microscope.

AIM: To determine the impact of age on the morphology of endothelial cells and central corneal thickness (CCT) in Chinese tree shrew. METHODS: One-hundred and twenty eyes of 60 healthy Chinese tree shrews were studied. Based on age, the tree shrews were divided into four groups. After general anesthesia, the images of endothelium were acquired using non-contact specular microscope Topcon 3000P. Eight parameters of corneal endothelial cells were measured by built-in software, including CCT, endothelial cell density (ECD), percent hexagonality (HG%), coefficient of variability (CV), size of minimal cell (Smin), size of maximal cell (Smax), average cells size (Savg) and size standard deviation (Ssd). Data were analyzed using STATA software. The differences of eight parameters among groups and correlations with age were analyzed. RESULTS: In all studied animals, the average CCT was 249.6±20.29 µm (202-301 µm), ECD was 3080.72± 460.76 cells/mm2 (1239.6-4047.6 cells/mm2) and CV was 29.10±7.60 (13.6-54.6). CV was significantly different among different groups (P<0.001). Strong correlation with age was found in ECD, Smax, Savg, Ssd and CV. CONCLUSION: Cornea of Chinese tree shrews had half CCT of human cornea and similar ECD, CV and size of corneal endothelial cells. Young adult tree shrews had higher ECD, HG% and low CV. ECD, Smax, Savg, Ssd and CV correlated with age significantly.