Numerical simulations show that the channels between the mismatched grains serve as an effective water permeation route. Our research will pave the way for large-scale graphene-based antifouling membranes for diverse water treatment applications.The inability of membranes to handle a wide spectrum of pollutants is an important unsolved problem for water treatment. Here we demonstrate water desalination via a membrane distillation process using a graphene membrane where water permeation is enabled by nanochannels of multilayer, mismatched, partially overlapping graphene grains. Graphene films derived from renewable oil exhibit significantly superior retention of water vapour flux and salt rejection rates, and a superior antifouling capability under a mixture of saline water containing contaminants such as oils and surfactants, compared to commercial distillation membranes. Moreover, real-world applicability of our membrane is demonstrated by processing sea water from Sydney Harbour over 72 h with macroscale membrane size of 4 cm Intrinsic limitations of nanoporous graphene limit its applications in water treatment. Here the authors produce post-treatment-free, low-cost graphene-based membranes from renewable biomass and demonstrate their high water permeance and antifouling properties using real seawater. Recent advances in post-synthesis reactive processing of chemical vapour deposition (CVD) graphene have produced atomically thin permeable films for water purification by creating randomly etched pores and nanoscale apertures in the graphene film4. However, these techniques involve a series of highly controlled, resource-intensive and complex procedures that are difficult to uniformly implement in high density and large scales. Thus, the capability of CVD graphene films for water purification and desalination remains restricted to small-scale demonstrations 2. Moreover, while CVD synthesis offers good control over the growth of graphene films, it remains an expensive process because of the necessity of compressed gases and extensive vacuum operation. Furthermore, often, hydrophobic nature of CVD graphene creates additional hurdles for utilisation in water purification membrane. Consequently, these technical challenges impede the commercial viability of CVD graphene films for water purification5.Graphene, an atomically thin carbon-based two-dimensional material, shows promise for a new class of ultrathin membranes that have atomically defined nanopores with diameters approaching those of hydrated ions. This characteristic is ideal for the design of membranes capable of ultrafast and selective water transport. A pristine single layer of graphene is impermeable to standard gases 6. In the MD process, water purification is driven by a vapour pressure gradient across a porous and hydrophobic membrane. This situation is created by parallel flows of a hot feed solution and permeate stream, where water vapour is formed at the interface of the membrane’s hot feed side and is transported to the opposing cold permeate side7. Key advantageous features of the MD process include water production almost independent of the feed solution salinity, and the potential to reject majority of non-volatile constituents, such as dissolved salt, organics, colloids and the ability to utilise low-grade waste heat to drive the process. These merits enable MD to be a promising green technology for zero liquid discharge purification processes8.MD is an rapidly emerging thermally driven water purification technology that is particularly promising for the treatment of seawater, industrial effluents and brine obtained from reverse osmosis and various desalination processes8. Recently, problem of energy-intensive process has been solved by implementing carbon nanotube/polymer composite as an effective pathway to locally generate the heat at the membrane interface9. Yet, the key membrane problem has not been fully addressed till now. Especially, when common chemical or oil-based contaminants are introduced during the MD process, membranes exhibit significant fouling behaviour that rapidly degrades the membrane performance and create irreversible degradation to the membrane11. Such fouling problem during MD operation reduces water recovery, fails to maintain contaminant rejection, increases the demand for harsh chemical cleaning and rapidly diminishes the lifetime of the membrane. Moreover, conventional MD membrane’s heat conduction across the membrane often leads to low water vapour flux with degradation of performance over a long period of operation that remains as another significant challenge12. Such limitations of conventional membranes necessitate new materials for antifouling membranes to successfully address these challenges. Improved MD membranes have been fabricated by several techniques such as phase inversion and electrospinning of polymers. However, most of these methods have been unable to achieve antifouling membranes that demonstrated high water vapour flux and long-term stability during MD operation under diverse mixtures of membrane-damaging contaminants14.MD has few but important major drawbacks that comes from an energy-intensive process of heating and maintaining the feedwater temperature and inability of MD membrane to handle diverse contaminant mixtures16. Recently, enhancements in the performance of water purification processes have been demonstrated with the incorporation of graphene flakes in the membranes17. However, until now, the extensive promises and potential of two-dimensional (2D) graphene films for water purification have not been realised.Despite the small intrinsic pores that restrict the water vapour passage, CVD graphene films possess numerous physiochemical properties that are valuable for MD application. These include its good mechanical strength, thermal and chemical stability, hydrophobicity and atomically thin thicknessIn this study, we present a low-cost, centimetre-scale CVD graphene membrane with inherent nanochannels to address these challenges. The graphene film is synthesised via a single-step, ambient-air CVD process derived using renewable source such as soybean oil. Graphene film is then directly used as an active layer in MD and exhibits high rates of water vapour flux, excellent salt rejection, long-term stability and sustained antifouling even in the presence of water contaminants , which rapidly degrade the performance of conventional commercial MD membranes. In addition, the graphene membrane demonstrates significantly superior performance compared to commercial MD membranes when processing seawater from Sydney Harbour. This performance is achieved without post-synthesis pore generation. Moreover, we show smart way to utilise often disadvantageous feature such as hydrophobicity in CVD graphene as an advantageous feature in emerging desalination and purification process such as MD. Through complementary microscopy, characterisation and computational simulations we propose a new mechanism in water vapour permeation in CVD graphene film through inherent nanochannels of mismatched overlapping grain boundaries.18, and then wet-transferred to a commercial polytetrafluoroethylene (PTFE) MD membrane. This process is described in Fig. 20. The source for the graphene growth is replaced with a low-cost, safe and renewable bio-source such as soybean oil. The ambient-air CVD process enables the growth of continuous graphene films with a high density of nanocrystalline grain boundaries on polycrystalline Ni substrate, which are desirable as water vapour-permeable channels. Finally, the graphene is wet-transferred onto a conventional supporting commercial PTFE MD membrane. A PMMA-assisted transfer is adopted, and PMMA is removed before testing the graphene-based membrane in water purification  and transmission electron microscopy  analysis of these nanochannels is constrained because of the multilayer thickness and small channel width compared to selected area aperture size.Importantly, we observe a slight overlap of domain boundaries in multiple regions of the sample—these serve as potential channels for the passage of water molecules  is conducted to determine the defect and the thickness uniformity in the films  at ~1350 cm−1, the graphitic peak that arise from the in-plane vibrational E2g mode of the sp2 carbon (G-band) at ~1580 cm−1, and the second-order 2D-band that arise from three-dimensional inter-planar stacking of hexagonal carbon network at ~2670 cm−126. The intensity ratios of ID/IG is 0.1–0.3 and that of I2D/IG is 0.6–1  membrane was carried out by direct contact MD (DCMD) using a range of solution mixtures including highly saline solutions with the presence of surfactants, mineral oil and real seawater collected from Sydney Harbour. The water vapour flux and salt rejection were measured to characterise the purification of water by the membranes. Performance of the permeable graphene-based membrane is benchmarked against the commercial PTFE MD membrane . The testing is carried out in a continuous, co-current crossflow system illustrated in Supplementary Fig. −1 NaCl, typical concentration of brine water), both the permeable graphene-based membrane and commercial PTFE membranes exhibit similar salt rejection, 99.9% after 72 h of operation. A relatively higher water vapour flux was observed for the permeable graphene-based membrane in comparison with the pristine PTFE-based MD membrane , but with a significant reduction in water flux from 40 L m−2 h−1 to 14.2 L m−2 h−1 over 32 h  and stable salt rejection (100%) over 72 h of MD operation under similar operation conditions ) cause detrimental pore fouling and/or membrane wetting, thus leading to inferior performance  for the 48 h of MD operation under similar conditions  and retention of water vapour flux  over 72 h, and a slight decrease in salt rejection  and long-term stability over 72 h  of MD operation , while maintaining a high water vapour flux  are introduced, suggesting that the proposed water transport process is feasible  solid nudged elastic band method, which is used to evaluate the energy barrier of water migration through graphene layers . The model is simplified by simulating one water molecule penetrating through the graphene layers as shown in Fig. −1 of sodium chloride (NaCl), water with 120 g L−1 of NaCl and one molecule (5 mM) of SDS, and finally water with 120 g L−1 of NaCl and two molecules (10 mM) of SDS. Higher concentrations of NaCl are used in the simulations as compared to the experiments to ensure sufficient interactions of the salt ions with the membrane, given the very short simulation time of 4 ns. Here, one or two SDS molecules are added in the feed, as the experimental scenario of 1 mM of SDS corresponds to either a single- or bi-molecular state of SDS29.The second computational study is based on molecular dynamics simulation (MDS). MDS resolves molecular length scales, and therefore provides a molecular picture of the transport of water molecules and rejection of salt ions through the graphene layers. The simulation domain and molecular construct of the permeable graphene-based membrane are shown in Figs. The dynamics of water molecules, NaCl and SDS ions can be observed in Supplementary Movie Unlike the previous studies where post-treatment techniques create nanopores in the graphene surface, we did not observe nanopores in our graphene microstructures. Rather we observed a multilayer graphene film with numerous graphene grain boundaries arising from the small domain sizes and numerous overlapping regions of adjacent graphene grains with the mismatched graphene grain boundaries.30. This is possible because flow resistance is much reduced when water or water vapour is transported between graphene sheets31. Multiple characterisations  show that our graphene film had variations in the number of layers over microscopic regions induced by mis-oriented, overlapping and sub-micron-sized grains. These structural features promote deformations  in graphene films32. Such nanoscopic wrinkling would increase the surface roughness of our graphene films and create suitable surface structures  to promote the water vapour entry and rapid permeation  conditions, which is 30 °C higher than elsewhere in this work. We placed a temperature probe as close as possible to each (feed and permeate) side of the membranes to measure the actual temperature difference across the both membranes as the vapour permeates. The results in Supplementary Fig. Another aspect of relevance to the MD process is heat conduction, which should be reduced across high-performance MD membranesx–y direction due to sp2 bonding in graphene lattice and poor thermal conduction in the z direction arising from weak van der Waals interaction35. This obviously favourable feature for MD applications requires further experimental and theoretical studies in near future.These results suggest potential additional advantages of using permeable graphene-based membranes in MD process under higher thermal load conditions. These findings are consistent with the fact that graphene is a two-dimensional nanomaterial with high anisotropy in thermal conductivity, where high thermal conductivity is observed in the 37.We have also studied the effect of graphene on the mechanical strength of the membrane. The results show only a marginal improvement compared to the pristine PTFE membrane , they show better antifouling and antiwetting performance compared to the highly hydrophobic surface of commercial PTFE-based MD membranes with the contact angle of 131.3° . The weak physisorption of the contaminant molecules on the graphene surface is overcome because of the kinetic energy provided by continuous feedwater flow.Some other factors could also reduce the blocking of the water passage channels by the contaminant molecules. To understand the antifouling nature of our permeable graphene film, we calculated the adsorption energy to investigate the interactions between the contaminant particles such as SDS with nanochannels at grain boundaries. The calculated adsorption energy To experimentally verify the weak physisorption interaction between SDS and the graphene surface, we have repeated the experiments with the pristine PTFE and the permeable graphene-based membranes with SDS/saline water mixtures for 72 h, and then samples were dried without any cleaning process and analysed using Raman spectroscopy. Knowing that SDS has clear and distinct Raman peaks, the areal mapping of SDS Raman intensities was then carried out to find out the relative difference in SDS adsorption on the pristine PTFE and permeable graphene membrane surfaces  excellent salt rejection (99.9%) when processing highly saline water , and exceptional antifouling properties by rejecting common water-born contaminants  over a prolonged period (48 and 72 h) of MD operation. Notably, we have also demonstrated the long-term, effective desalination of seawater, directly sourced from Sydney Harbour. Synergistic integration of our graphene films provided solutions to membrane problems persisted in MD as well as exhibiting significant advantages over widely used commercial MD membranes . The outcomes of this work may near commercial applications of CVD graphene films in water purification, and also demonstrate the benefits of using 2D materials as advanced membranes for water purification and desalination.Utilisation of CVD graphene in water purification has remained limited in both research and industrial scales because of difficulties in precise pore engineering, high production costs and the hydrophobic nature of graphene films. In this work, the above challenges have been addressed by the low-cost, green  and resource-efficient  synthesis of permeable graphene films. Importantly, the synthesised graphene films possess a high density of nanochannels that are distributed across the submicrometre domains. Without any post-synthesis pore engineering, the permeable graphene films demonstrate high-water flux  were used as the growth substrate. The experimental schematic is shown in Fig. Mw 996,000 Sigma-Aldrich) was spin-coated onto the as-grown graphene on Ni foil (3000 rpm for 1 min). The sample was then dried in open air for 12 h. Subsequently, the underlying Ni foil was dissolved in 1 M FeCl3 in 30 min. The PMMA/graphene film then floated to the surface. This was washed several times with deionized (DI) water. Next, the PMMA/graphene was lifted off from the DI water bath and transferred onto the membrane substrate. The PMMA was then dissolved with acetone, and the sample is rinsed with DI water.A poly (methyl methacrylate) (PMMA)-assisted transfer of graphene was adopted. Briefly, 46 mg/mL of PMMA (2. AFM images were acquired with an Asylum Research MFP-3D AFM operating in intermittent contact (tapping) mode with a Budget Sensors TAP150Al-G cantilever . Image analysis was performed using the Scanning Probe Image Processor (SPIPTM) software produced by Image Metrology A/S. Energy-filtered TEM was performed using a JEOL 2200FS TEM microscope operated at 200 kV. Optical images were obtained with an Olympus BX51 optical microscope. Transmittance measurements were obtained using a Varian Cary 5000 UV–Vis spectrophotometer. A graphene area of 2 cm2 was used, and optical spectra were recorded in the wavelength range from 300 to 800 nm.Raman spectroscopy was performed using a Renishaw inVia spectrometer with Ar laser excitation at 514 nm and a probing spot size of ~1 µm2. Temperatures of feed and distillate solutions were controlled by two heater/chillers , and were continuously recorded by temperature sensors that were inserted at the inlet and outlet of the membrane cell. Both feed and distillate streams were concurrently circulated by two gear pumps. The same crossflow rate of 30 L h−1 (corresponding to the crossflow velocity of 9 cm s−1) was applied to both feed and distillate simultaneously in order to minimise the pressure difference across the MD membrane. Weight change of the distillate tank was recorded by an electronic balance  with a data logger. All piping used in the DCMD test unit was covered with insulation foam to minimise heat loss.DCMD was conducted using a closed-loop bench-scale membrane test apparatus  and real seawater, respectively. The comparison between the mineral oil and light crude oil is tabulated in Supplementary Table MD fouling experiments were conducted using four types of saline water and saline water with contaminant mixtures: 70 g LΔT = 70 °C) measurements, the feed solution temperature was 90 °C, while the distillate temperature was also 20 °C. To measure the actual temperature difference across the membranes as the vapour permeates, a temperature probe was placed as close as possible to each (feed and permeate) side of the membranes. A new membrane sample was used for each experiment. Water vapour flux was recorded with a digital balance continuously. Conductivity of the distillate was measured by a conductivity meter  every 5 min. All feed solutions were processed by DCMD for 72 h, except for the cases of mineral oil tests that was performed for 48 h and the case where we demonstrate long-term stability with real sea water feed, which was performed for 120 h. TOC was analysed using a TOC/TN analyser . Membrane surface charge was measured by a SurPASS electrokinetic analyser . Zeta potential of the membrane surface was calculated from the measured streaming potential using the Fairbrother-Maastin approach. All streaming potential measurements were performed in a background electrolyte solution . The background solution was also used to completely flush the cell before pH titration using either hydrochloric acid (0.5 M) or potassium hydroxide (0.5 M). Surface energy of the membranes were calculated by measuring the contact angle using three different liquids (two polar and one non-polar) of well-known surface tension, employing the Lifshitz van der Walls (non-polar) and Lewis acid–base (polar) approaches40. Commercial PVDF MD membrane  experiments were carried out in same experimental protocol as PTFE membrane case.Feed and distillate volumes of 4 and 1 L were used, respectively. The temperature of inlet feed solution is 60 °C, while that of the distillate inlet stream is 20 °C in most of the experiments. In the high temperature gradient  is used as exchange correlation functional43. A damped van der Waals correction was incorporated using Grimme’s scheme44 to better describe the non-bonding interaction. The projector-augmented-wave method45 was used to describe the electron−ion interaction and the plane-wave energy cutoff was set to 400 eV. A vacuum layer with a thickness of at least 15 Å was used. Atoms were relaxed until the residual force and energy converged to 0.01 eV/Å and 5 × 10−5 eV, respectively. A Γ-centred k-point mesh46 of 1 × 1 × 1 was used for sampling in the first Brillouin zone. The energy barrier for H2O migration through the graphene sheets was obtained by using the climbing image-nudged elastic band (CI-NEB) method47. For the graphene grain boundaries, the adsorption energy Ead of the SDS and H2O molecule is obtained according toEcomb, Ebound and Emo represent the total energy of the SDS molecule/H2O-adsorbed graphene boundary, pure graphene boundary and the SDS or water molecule, respectively.First-principles calculations were performed based on the density functional theory (DFT) using the plane-wave basis VASP code48 is used for the MDS computations and visual molecular dynamics (VMD)49 is used to visualise the computed results. The boundary conditions are periodic in all three dimensions, with a simulation cell depicted in Fig. 3, and the pistons are allowed to move in the x direction under zero differential pressure. The membrane is constructed from four graphene sheets with a slit size between each sheets of 7 Å, and an overlapping size of 3 Å, as shown in Fig. 50. For the SDS molecules, the force field described by Tummala and Striolo is employed in our study51. The Lennard–Jones (L–J) potentials for the sodium ions, chlorine ions and carbon atoms are adapted51. The intermolecular L–J interactions are then computed using the Lorentz–Berthelot mixing rule. In this study, the membrane carbon atoms are kept fixed in position. A more detailed description of the force potentials used can be found in Supplementary Table The large-scale atomic/molecular massively parallel simulatorThe data that support the findings of this study are available from the authors upon request.Supplementary InformationDescription of Additional Supplementary FilesSupplementary Movie 1Supplementary Movie 2Supplementary Movie 3


Recently, functionalized graphene, a kind of gas sensing material, has been reported to show good application prospects in the gas sensor field. Therefore, calculations were performed to analyze the gas sensing properties of intrinsic graphene (Int-graphene) and functionalized graphene-based material, Ag-decorated graphene (Ag-graphene), for decomposition products of SF6, including SO2F2, SOF2, and SO2, based on density functional theory (DFT). We thoroughly investigated a series of parameters presenting gas-sensing properties of adsorbing process about gas molecule  and double gas molecules  on Ag-graphene, including adsorption energy, net charge transfer, electronic state density, and the highest and lowest unoccupied molecular orbital. The results showed that the Ag atom significantly enhances the electrochemical reactivity of graphene, reflected in the change of conductivity during the adsorption process. SO2F2 and SO2 gas molecules on Ag-graphene presented chemisorption, and the adsorption strength was SO2F2 > SO2, while SOF2 absorption on Ag-graphene was physical adsorption. Thus, we concluded that Ag-graphene showed good selectivity and high sensitivity to SO2F2. The results can provide a helpful guide in exploring Ag-graphene material in experiments for monitoring the insulation status of SF6-insulated equipment based on detecting decomposition products of SF6.Detection of decomposition products of sulfur hexafluoride (SF The theory suggested that decorated Ag could effectively improve the electron density and charge transfer characteristics of graphene, which provided a new way of preparing sensing materials for functionalized graphene gas and developing a high-performance gas sensor for detection of SF6 decomposition products.Based on density functional theory (DFT), adsorption processes of single  to build the graphene structure, and the periodic boundary condition of supercell was set to 20 Å to avoid the interaction between adjacent layers in modeling. Then, optimization calculation was conducted for the gas molecule structure and the supercell to adjust their structure parameters in the model to be as close to the experimental parameters as possible. To find the most stable Int-graphene and Ag-graphene structure after adsorbing gas molecules, the system of gas molecules on Int-graphene and Ag-graphene was calculated and optimized. Finally, obtained adsorption systems were analyzed by a series of physical and chemical characteristic parameters. Because the Van der Waals force shows obvious effects in physical adsorption, this work selected the generalized gradient approximation method, using Perdew-Burke-Ernzehof format and dispersion correction for DFT algorithm to process exchange correlation and iteration process, respectively [k-point mesh of 6 × 6 × 1 was selected for the Brillouin zone integration to obtain accurate energies and structures; and the convergence tolerance of energy was 2.72 × 10−5 eV in structural optimization [All calculations were based on DMolectively . Thus, tmization . Previoumization . After presenting the optimization structure, a series of physical and chemical parameters were analyzed to understand the adsorption process of gas molecules on Int-graphene and Ag-graphene. Their definitions are as follows:ads), the acting force of gas molecules adsorbed on Int-graphene and Ag-graphene, gives the change of total energy in the adsorption process of gas molecules on Int-graphene and Ag-graphene to reach the most stable adsorption system using the equation:(system), E(Int-graphene/Ag-graphene), and E(molecule) are the total energy of adsorption system after the molecules adsorbed on graphene or Ag-graphene, the energy of graphene or Ag-graphene, and the energy of gas molecules, respectively.Adsorption distance (d) means the closest distance from Int-graphene or Ag-graphene to gas molecules. Adsorption energy (∆ENet charge transfer (Q) characterizes the quantity of electric charge transferred from gas molecules to Int-graphene or Ag-graphene in the absorption process and reflects the change of electrical properties of Int-graphene and Ag-graphene. The energy gap of adsorption system offers the complexity of electron transfer between the whole highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), and its formula is as follows:6 characteristic decomposition  and Int-graphene were constructed in material visualizer. Then, every geometrical structure was optimized by finding its lowest energy, so bond length and angle were marked in each optimized gas molecule model , E (Ag), and E (Ag/C72) represent the respective energy of intrinsic graphene, energy of a single Ag atom, and the total energy of optimized Ag-graphene.The binding energy describes the natural interaction of the bonding between decorated Ag and graphene as:6 decomposition products, which was verified and used in previous similar studies [ studies .Z-direction and forms covalent bonds with its adjacent C atoms with 2.053 Å bond length. This further supports the idea that an Ag-decorated graphene structure has a local sp3 configuration. Otherwise, the similar decorated structures of local sp3 configuration were also found in other metal-element-decorated graphene , and it is generally believed that local sp3 configuration is correct in metal-doped graphene theory research [research .2F2, SOF2, and SO2) adsorption with different initial positions. We focused on a series of parameters presenting gas-sensing properties of adsorption process, such as d, ∆Eads, and Q. To have a better understanding of adsorption effects of gas molecules on Ag-graphene, we first investigated single gas molecule  were −0.004 e, −0.002 e and −0.003 e in graphene/SO2F2, graphene/SOF2 and graphene/SO2, respectively. Consequently, the interaction for gas molecule adsorption on graphene is just van der Waals interactions, which are too weak to influence the change of conductivity in the gas adsorption process. Therefore, intrinsic graphene material is not suitable for decomposition component detection in SF6-insulated equipment. Thus, we do not further discuss the adsorption details for gas molecules adsorption on intrinsic graphene.As shown in 2F2, SOF2 and SO2) were made closer to Ag-graphene with different initial positions. We computed same parameters to analyze the gas-sensing properties of the adsorbing process. These optimized stable adsorption systems are exhibited in To obtain the most stable adsorption system, single gas molecules  had far exceeded the critical value of chemical adsorption (0.8 eV) [As shown in (0.8 eV) .2. 2 came close to Ag-graphene, the F atom tried to separate from SOF2, so the S-F bond was stretched to 2.718 Å, which offered a chance to build a new bond between Ag interacted, and lone F and left S atoms, respectively. However, these interactions were some kind of physical adsorption because of low Van der Waals force with bonding energy (−0.678 eV). In addition, the value of Q upon SOF2 adsorption on Ag-graphene was only −0.351 e. This agrees with the conclusion about physical adsorption, which indicates that electron also transfers from Ag-graphene to gas molecule. However, a different case happened with SOF2 adsorption did not show obvious changes on molecular gas structure  was lower than that of Ag-graphene/SO2F2, but higher than that of Ag-graphene/SOF2. Similarly, the value of Q (−0.801 e) upon SO2 adsorption on Ag-graphene was the middle value among three cases. Therefore, SO2 exhibited chemisorption with Ag-graphene.SOture see . While tNet charge transfer has an effect on the density of states (DOS), which results in the change of conductance in system. Thus, the density of states (DOS) and its corresponding partial DOS (PDOS) of Ag-graphene before and after adsorption were calculated to further analyze the chemical adsorption mechanism of gas on Ag-graphene.2F2 adsorption by comparison, as shown in 2F2 system. 2F2 in a certain filling rate degree, which bring a strong interaction between SO2F2 and decorated Ag.DOS change was evident before and after SO2 only occurred below the Fermi level with a slight increase  are shown in We investigated the transition ability of electrons from the top of valence band to the bottom of conduction band and electronic structure through HOMO and LUMO. The calculation results of HOMO and LUMO of Ag-graphene structure before and after absorbing SF2F2 was adsorbed on Ag-graphene, the energy gap of Ag-graphene/SO2F2 increased to 0.761 eV, which indicated that the SO2F2 adsorption greatly increased system conductivity. After SO2 was adsorbed, the energy gap of the system slightly increased to 0.359 eV, which supported that conductivity of the Ag-graphene/SO2 increased to a certain extent. However, SOF2 adsorption almost had no effect on changing the energy gap of the system. All cases were consistent with the conclusion obtained through DOS analysis above.Before absorbing gas molecules, the HOMO and LUMO of Ag-graphene were mainly distributed at the Ag-decorated site and its opposite site in 2F2, 2SOF2, and 2SO2) adsorbed in favorable positions on Ag-graphene. Optimized systems  are shown in Before understanding the mechanism of gas molecules interaction with Ag-graphene, it was necessary to explore whether more gas molecules could be adsorbed onto the Ag-graphene surface. Thus, we constructed all kinds of configurations with two gas molecules  are −1.448 eV and −1.365 eV, and net charge transfers (Q) are −1.084 e and −1.113 e in Ag-Graphene/SO2F2 and Ag-Graphene/2SO2F2, respectively. By comparison, the adsorption process of double gas molecules is basically similar to that of the corresponding single gas molecule.As shown in 2 came close to Ag-Graphene with the S-F bond extended to 1.702 Å, the second SOF2 kept its molecule structure unchanged. As the adsorption distance (d) for single gas molecule of SOF2 was 0.051 Å shorter than that of a double gas molecule  of Ag-Graphene/2SO2 (−0.701 eV) were twice as much as that of Ag-Graphene/SO2 (−0.350 e) with considerable adsorption energy (∆Eads) of Ag-Graphene/2SO2 (−1.465 eV). Thus, new Ag–S and Ag–O bonds were formed, which led to electron enrichment of the Ag-graphene. These results reveal that more gas molecules were involved in interaction than Ag-Graphene/SO2.However, an S atom from one SO2F2, 2SOF2, and 2SO2) adsorbed on Ag-graphene. The adsorption results of double gas molecules are similar to that of single gas molecule adsorption; HOMO and LUMO energies declined after adsorbing gas molecules. When 2SO2F2 gas molecules were adsorbed on Ag-graphene, energy gap width increased to 1.050 eV, as shown in 2F2 gas molecules made conductivity rise further. The HOMO gathered in SO2F, and all of LUMOs were located at Ag-graphene  on Ag-graphene based on density functional theory. A series of parameters presenting the adsorption characteristics in the adsorption process were calculated, and the main conclusions of the adsorption process were obtained as follows:(1)After calculating and comparing the binding energy of three different Ag atom adsorption positions on graphene, the T-site was the best decorated location for Ag atom.(2)Comparing with weak gas molecule interaction with Int-graphene, the Ag atom significantly enhances the electrochemical reactivity of graphene, reflected in the change of conductivity during the adsorption process.(3)2 and SO2F2 gas molecules were adsorbed on Ag-graphene with strong chemical adsorption effect, and the interaction strength decreased in following order: SO2F2 > SO2. Also, Ag-graphene physically interacted with SOF2. The information from DOS, HOMO, and LUMO supported the conclusion that the electrical resistivity of the system was reduced during the adsorption process.For single gas molecule adsorption, SO(4)2F2 or 2SOF2 were near Ag-graphene. However, the adsorption energy and net charge transfer were significantly improved compared with that of single gas molecule adsorption. Based on the system conductivity change, the electrical conductivity of the system would further increase with the increase of adsorbed molecules (2SO2F2 and 2SOF2).The adsorption results of double gas molecules were similar to those of single gas molecules, and the increase of the number of molecules did not change the type of interaction. The decorating Ag atom only provided one adsorption site, so that only one gas molecule could be adsorbed on Ag-graphene when 2SOIn summary, we mainly investigated the adsorption properties and mechanism for decomposition into SF2F2, a kind of decomposition product of SF6. Results of theoretical study played a guiding role in preparing a gas sensor with strong selectivity and high sensitivity in the experiment. Meanwhile, the conclusions are beneficial to realizing online monitoring and diagnosis of SF6-insulated equipment in engineering.Thus, Ag-graphene showed distinct interaction with SO


The sensitivity of silicon nanopillar array for relative humidity (RH) with UV illumination was investigated in this work. The silicon nanopillar array was prepared by nanosphere lithography. Electrical measurements were performed on its sensing performance with and without UV irradiation. It was found that UV light improved the humidity sensitivity with different UV light wavelengths and power. The sensor response and recovery time were reduced. Furthermore, the turn-on threshold voltage and the operating voltage both decreased. These sensing characteristics can mainly be attributed to the electron-hole pairs generated by UV light. These electron-hole pairs promote the adsorption and desorption processes. The results indicate that silicon nanopillar array materials with UV irradiation might be competitive as novel sensing materials for fabricating humidity sensors with high performances. Unlike other gas sensors, which are used to detect organic vapour gas and hazardous gas, a humidity sensor can monitor the environmental moisture for human comfort. It can also be used in automotive, medical, and food processing industries. So, humidity sensors have attracted much attention in recent years ,5,6,7,8.2 ,10, WO3 2 [3 ,12, ZnO 2 [3 ,14, and 2 [3 [2 ,16 have Meanwhile, many methods, such as applying a high electric field across the sensor terminals , doping In previously published papers, it has been reported that an effective pathway for gas transportation could be built into a silicon nanopillar array (Si-NPA) sensor, which shows high humility sensitivity, a short response/recovery time, and a low operating voltage ,24,25,262 gas under a Radio Frequency (RF) power of 20W. In this RIE process, the size of the nanospheres was reduced. In the next step, the substrate was etched by using 40 sccm CF4 gas under a RF power of 40 W. Then, the large-area ordered Si nanopillar array can be obtained. Finally, the PS nanospheres were removed in tetrahydrofuran (THF). An aluminum comb-like electrode was prepared by electron-beam evaporation on the top of the Si-NPA. The process of EBV was performed at a 5 × 10−4 Pa vacuum, and the evaporation current was 25 mA. Si-NPA was prepared by nanosphere lithography. In the first step, a single layer of polystyrene (PS) spheres was covered on the P-Si substrate. The PS spheres with a diameter of 220 nm in the investigation were purchased from the Duke Scientific Corporation as 10% by wt. in solution with standard deviations between 5% and 7%. About 3 ~ 5 μL of solution that was diluted by mixing with an equal amount of ethanol was applied on the silicon substrate, which was kept in 10% dodecyl sodium sulfate solution for 24 h previously for a hydrophilic surface. Then, the substrate was slowly immersed into the deionized water at less than 45 degrees, and PS nanospheres formed an unordered monolayer on the water surface. Next, about 3 μL of 5% dodecyl sodium sulfate solution was added into the water in order to change the water surface tension, and an ordered monolayer was obtained. Last, the monolayer was then lifted off from the water surface to the silicon wafer. In the second step, the coated substrates with a pattern made of PS nanospheres were etched in the reaction ion etching (RIE) system  by using 20 sccm of OThe UV LEDs with different wavelengths and power were used in the work. 0 is the final/initial values. The response time is defined as the time spent from R/R0 = 10% to 100% when the sample was taken in the quartz glass. In contrast, the recovery time is defined as the time spent from R/R0 = 100% to 10% when the sample was removed from the quartz glass. The response and recovery time was studied. The hysteresis was studied in the work, which refers to an important indicator of the performance of the humidity sensor. The stability is an important indicator of the performance of the humidity sensor, and the study of stability was performed after the sensors were exposed to air for 24 weeks. In conclusion, the Si nanopillar array as a gas sensing material was fabricated by nanosphere lithography. The measurement of the room temperature humidity sensitivity of the Si nanopillar sensor without and with UV light irradiation was performed. The results show that the turn-on threshold voltage decreased from 1 V to 0.5 V, and the operating voltage decreased from 3 V to 1 V. Furthermore, UV light improved the sensitivity with different UV light wavelengths, power, and distance. The relative humidity could be detected under 10% RH, and the sensor response and recovery time were reduced. The hysteresis for Si-NPA with UV irradiation is small. The humidity sensor stability with UV irradiation is better. These sensing characteristics indicate that the Si-NPA with UV irradiation might be a promising candidate for fabricating high-performance humidity sensors.


Staphylococcus aureus (MSSA) between 2011 and 2016 were analyzed for surveillance.In vitro trends of cefazolin and ceftriaxone susceptibilities from pediatric clinical isolates of methicillin-susceptible Our laboratory continues to use agar disk diffusion for staphylococcal susceptibilities applying Clinical Laboratory Standard Institute’s 2012 breakpoints.A total of 3992 MSSA clinical isolates in the last 6 years were analyzed for their in vitro cefazolin and ceftriaxone susceptibilities. While all MSSA isolates exhibited cefazolin susceptibilities within the “susceptible” zone range, there have been a proportion of isolates with ceftriaxone susceptibilities falling in “intermediate” zones, ranging from 2.6% in 2011 to 8.3% in 2016.Cefazolin continues to be the recommended agent for MSSA treatment at our institution, reflected by the finding that only 2% (6/321) of patients who received ceftriaxone as definitive therapy for MSSA bacteremia during the study period. We have confirmed the cefoxitin-predicted MSSA susceptibility to cefazolin, but have found concerning drifts in ceftriaxone susceptibilities by continued in vitro monitoring over the last 6 years.The online version of this article (10.1186/s12941-018-0257-x) contains supplementary material, which is available to authorized users. Staphylococcus aureus to β-lactam antibiotics has been well-characterized starting from the first uses of penicillin [mecA- and vanA-determined mechanisms to alter the components of cell wall synthesis [mecA confers the majority of resistance to penicillinase-stable β-lactams [β-lactam antibiotic breakpoints for methicillin-susceptible S. aureus (MSSA), except oxacillin, cefoxitin, penicillin, and ceftaroline [β-lactams can be inferred using the above agents. Following this recommendation, there have been a few small in vitro and clinical studies that have examined the question of “inferred susceptibility” for MSSA [The development of resistance of nicillin . This fiynthesis , 3. The -lactams . For ove-lactams . In Janutaroline . This refor MSSA –10. ThisStaphylococcus spp. for more than 20 years. The susceptibility panel included antibiotic disks : penicillin (10 units), oxacillin  or cefoxitin (30 μg after 2011), amoxicillin/clavulanate (20/10 μg), cefazolin (10 μg), ceftriaxone (10 μg), meropenem (10 μg), gentamicin (10 μg), erythromycin (15 μg), clindamycin (2 μg), ciprofloxacin (5 μg), rifampin (5 μg), sulfamethoxazole-trimethoprim , linezolid (30 μg), and vancomycin . Nitrofurantoin (300 μg) is tested and reported in urine isolates only, while erythromycin and clindamycin are not reported in urine isolates. Our lab has continued to test for, and report, cefazolin and ceftriaxone susceptibility for MSSA isolates using the 2012 CLSI breakpoints [S. aureus ATCC 25923 for disk diffusion and S. aureus ATCC 29213 for Etest tested on Mueller–Hinton agar  with acceptable in-range limits  to identify a subset of patients that had MSSA-positive blood cultures and received ceftriaxone during this period. We then reviewed patient medical records to determine whether ceftriaxone was used as definitive therapy.A total of 3992 MSSA isolates tested between 2011 and 2016 were included in the susceptibility analysis. Using 2012 CLSI criteria, we confirmed that cefazolin remained an active agent, with all zone interpretive range confined above the “susceptible range of ≥ 19 mm (susceptible: ≥ 18 mm), and none in “intermediate” range of 15–17 mm (data not shown). We also found that a proportion of MSSA isolates produced ceftriaxone susceptibilities in “intermediate” zones ranges (14–20 mm) over the 6 year period, from 2.6% in 2011 to 8.3% in 2016 with the highest of 15.5% in 2014 , were observed to be 8.0% in “intermediate” range to ceftriaxone. This fraction reduced to 3.1% when S. saprophyticus isolates (n = 80) were excluded, which accounted for the majority of MS-CoNS ceftriaxone non-susceptibility in our study. No “intermediate” range susceptibility to cefazolin was observed in MS-CoNS isolates, which was 100% sensitive over the course of our study (data not shown).When ceftriaxone susceptibilities were further broken down by site of culture, we found that while blood, respiratory, and wound/deep tissue infections had similar proportion of MSSA isolates with ceftriaxone “intermediate” at 6.30, 6.82, and 6.15% respectively, the MSSA strains isolated from urine cultures showed higher rate of non-susceptibility to ceftriaxone  without evidence of treatment failure.β-lactams like cefazolin and nafcillin are superior to vancomycin for treatment of MSSA” since mid-2013. This has, in part, resulted in our low number of cases where ceftriaxone was used as the definitive therapy. This hinders our ability to assess the clinical implications of ceftriaxone non-susceptibility (or “intermediate”), as all patients who received ceftriaxone as definitive therapy had known-susceptible isolates due to our cephalosporin susceptibility testing and reporting practices.Our institutional Antimicrobial Stewardship Committee has implemented a Microbiology Result Comment of “β-lactams, using “inferred susceptibility” [Ceftriaxone is not a first-line agent for MSSA infections, but its favorable dosing parameters often makes it a favorable choice in outpatient management. While there are no randomized controlled trials examining its effectiveness in treating MSSA infections, there have been small observational studies examining clinical outcomes, though it is not apparent that these studies tested for in vitro ceftriaxone non-susceptibility. One retrospective study from Israel investigated treatment of MSSA bacteremia in 541 patients with different ibility” . Ceftriaibility” . Lastly,ibility” . These smecA-independent mechanism in MSSA and MS-CoNS conferring their reduced susceptibility to certain β-lactams, similar to the ever-emerging multitude of resistance in Gram-negative bacteria. This may need to be addressed for surveillance purposes. Interestingly, ceftriaxone non-susceptibility was not as pronounced in MS-CoNS, except for S. saprophyticus, which has a low overall prevalence of mecA positivity [The low historical prevalence of MSSA resistance to cefazolin, ceftriaxone and other antistaphylococcal β-lactams is well-described , and refsitivity .This study affirms that cefazolin should continue to be the first line choice for the treatment of MSSA infections, and its inferred in vitro susceptibility from cefoxitin is still accurate. Our observed drift in ceftriaxone in vitro susceptibilities serves as an awareness call for closer surveillance. Additional studies at other institutions are necessary to determine if this trend is wide-spread. Consistent with CLSI recommendations, laboratory testing of antimicrobial susceptibility not only plays a role in patient care but also epidemiology surveillance for emergence of resistance.Additional file 1: Figure S1. Quality control performances of weekly cefoxitin, cefazolin, and ceftriaxone disk diffusion the study period. Figure S2. Post hoc measurement of zones of inhibition generated from ceftriaxone and cefazolin disks against clinical isolates (n = 153) of MSSA. Heterogeneous or “beach”-type of zone phenotypes around ceftriaxone disk could be sized typically by either at ~ 80% growth inhibition or at the complete growth inhibition (Note: The measurement at the complete growth inhibition has been the standard for susceptibility interpretations). Insert graph shows “cliff”-type of homogeneous zone measurements around cefazolin disk.


Blockade of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) has been used as cancer immunotherapy in recent years, with the blockade of PD-1 being more widely used than blockade of PD-L1. PD-1 and PD-L1 blockade therapy showed benefits in patients with various types of cancer; however, such beneficial effects were seen only in a subgroup of patients. Improving the efficacy of PD-1 and PD-L1 blockade therapy is clearly needed. In this review, we summarize the recent studies on the effects of gut microbiota on PD-1 and PD-L1 blockade and discuss the new perspectives on improving efficacy of PD-1 and PD-L1 blockade therapy in cancer treatment through modulating gut microbiota. We also discuss the possibility that chronic infections or inflammation may impact on PD-1 and PD-L1 blockade therapy. The immune system uses various effector cells and molecules to control and eradicate infectious agents and cancer cells. Cytotoxic T cells (CTL) are the major effector cells in anti-tumor immune responses , 2. HoweProgrammed death 1, also known as cluster of differentiation 279 (CD279), is a cell surface receptor that was discovered in 1992 . PD-L1 aProgrammed death 1 is expressed on T, B cells, and myeloid cells . PD-L1 iProgrammed death 1 and its ligands are members of the immune checkpoint proteins delivering inhibitory signals to activated T cells. The interaction of PD-1 with PD-L1 or PD-L2 leads to suppression of T cells, a regulatory mechanism to prevent overstimulation of immune responses and autoimmunity , 16–21. In anti-tumor immune responses, the tumor antigens generated by gene mutations, are recognized by the immune system and specific CD8+ CTLs targeting tumor antigens are generated . These sHowever, tumor cells employ various strategies to escape the attack from the immune system, one of which is to resist the killing effects from the anti-tumor CTLs by increasing PD-L1 expression in tumor tissues , 23, 24.via multiple mechanisms, such as promoting T cell apoptosis, anergy, and exhaustion . They also showed that the growth of PD-L1 positive murine tumors in syngeneic mice was suppressed by an anti-murine PD-L1 mAb . Other rTo date, the U.S. Food and Drug Administration (FDA) has approved the use of five monoclonal antibodies targeting PD-L1 or PD-1 in cancer treatment. The details of the clinical trials of these five monoclonal antibodies are summarized in Table A very interesting study by Sivan et al. provided strong evidence that the efficacy of PD-L1 blockage therapy can be improved by the modulation of gut microbiota . In thisBifidobacterium species, particularly Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium adolescentis as the candidate species. The role of these Bifidobacterium species in enhancing protective immunity against tumors were further investigated by administering TAC mice bearing established tumors with a cocktail of Bifidobacterium species containing B. breve and B. longum by oral gavage. This experiment resulted in Bifidobacterium-treated mice having significantly improved tumor control as compared to mice that did not receive Bifidobacterium. Sivan et al. also showed that the possible mechanisms by which Bifidobacterium species inhibited tumor growth were through activating DCs, which in turn, improves the effector function of tumor-specific CD8+ T cells. Given that the enhanced anti-melanoma effect from Bifidobacterium species had occurred at the innate immunity level, the authors anticipated that Bifidobacterium species also provide anti-tumor beneficial effects to other types of tumors. However, the mechanisms by which Bifidobacterium species activated DCs improved the effects of anti-tumor CD8+ cells still need to be clarified.They first showed that prophylactic transfer of fecal material from JAX mice to TAC mice was sufficient to delay tumor growth. To examine whether microbial community alone was effective as a therapy, they administered fecal material from JAX mice alone or in combination with anti-PD-L1 mAbs to TAC mice. These experiments showed that fecal material alone was sufficient to significantly inhibit tumor growth and that the combination treatment further improved tumor control. To identify the responsible bacterial species, they used 16S ribosomal RNA (16S rRNA) sequencing and identified B. longum, Collinsella aerofaciens, and Enterococcus faecium were more abundant in the anti-PD-1 immunotherapy responders, supporting the anti-tumor effects of Bifidobacterium species , their gut microbiota enriched with Dorea formicogenerans. However, the mechanisms responsible for these changes are not clear. Studies comparing the gut microbiota changes prior to and following anti-PD-1 therapy of individual patients are required, which will provide information regarding whether anti-PD-1 antibodies directly affect gut bacterial species.Several additional studies also compared the gut microbiota in patients with metastatic melanoma receiving anti-PD-1 therapy. A recent study by Frankel et al. using metagenomic shotgun sequencing method showed that melanoma patients who responded to immune checkpoint inhibitors were enriched with s caccae . FurtherClostridiales, and the non-responders had a higher abundance of Bacteroidales. In a very recent study with multiple first authors and J. A. Wargo being the responding author, they further compared the gut microbiota of patients with metastatic melanoma receiving anti-PD-1 therapy (Ruminococcaceae family, which belongs to the Clostridiales order, as compared to patients who did not respond to the therapy. Furthermore, they performed fecal microbiota transplantation experiments in germ-free mice, in which they showed that germ-free mice transplanted with stool samples from patients who responded to anti-PD-1 and anti-PD-L1 therapy had a significantly reduced tumor growth and improved responses to anti-PD-1 and anti-PD-L1 therapy, coupled with a higher density of CD8+ T cells. However, it is not clear which bacterial species in the Ruminococcaceae family has played the role in enhancing the PD-1 blockade therapy.A study by Wargo et al. examined the human gut microbiota and metabolites of metastatic melanoma patients who received anti-PD-1 therapy using 16S rRNA and whole genome shotgun sequencing . They fo therapy . They foAkkermansia muciniphila was enriched in patients who responded to anti-PD-1 therapy. This suggests that A. muciniphila may enhance patient response to PD-1 blockade therapy. They verified this observation by transplanting the patients stool samples in specific pathogen-free mice or germ-free mice and observed tumor growth in these mice. They also found that A. muciniphila alone was able to restore the anti-tumor effects of PD-1 blockade that was inhibited by antibiotics. However, the mechanism by which A. muciniphila enhancing PD-1 blockade therapy is not known.Another recent study by Routy et al. investigated the effects of gut microbiota in PD-1 blockade therapy . In theiBacterial species that are positively associated with PD-1 and PD-L1 blockade therapy are summarized in Table Despite the exciting findings in this research field, the underlying molecular mechanisms by which the identified gut bacterial species in the above studies enhance PD-1 and PD-L1 blockade therapy remain largely unknown.via the IL-12 pathway, suggesting that gut bacterial species that are positively associated with PD-1 and PD-L1 blockade therapy may release components that directly downregulate PD-1 or PD-L1 expression (Recently, unmethylated CpG oligodeoxynucleotides, which are abundant in bacterial DNA, were found to enhance CD8+ T cell anti-tumor immunity by downregulating PD-1 expression pression , 79.Escherichia coli in these animals was able to recruit sufficient DCs to the intestines (Bacteroides fragilis was found to induce the Th1 response (Bifidobacterium species that inhibited tumor growth activated DCs, further supporting this view (It is also possible that the gut bacterial species indirectly affect PD-1 and PD-L1 expression through locally or systematically regulating immune responses, thereby affecting the efficacy of PD-1 and PD-L1 blockade therapy. Gut microbiota has been shown to impact on both innate and adaptive immune cells. Germ-free animals had a reduced number of intestinal DCs and administration of testines , 81. In testines . Germ-frtestines , 84. Polresponse . Reductiresponse . The finhis view .Several microbes cause chronic infections in humans, some of which are known to increase host PD-1 and PD-L1 expression –94. HoweHelicobacter pylori infection. H. pylori are a Gram-negative bacterium that colonizes the stomach of more than 50% of the world population. While most of the individuals colonized with H. pylori are asymptomatic, some may develop chronic gastritis and peptic ulcers, and H. pylori colonization is also a risk factor for gastric cancer (H. pylori infection have a significantly higher level of pro-inflammatory cytokines, such as TNF-α (H. pylori increased the gastric epithelial expression of PD-L1 using a gastric epithelial cell line model (H. pylori inhibited the proliferation of CD4+ T cells isolated from blood and the inhibitory effect can be blocked using antibodies PD-L1. Similarly, Wu et al. observed increased PD-L1 expression in gastric biopsies of individuals infected with H. pylori, and co-culture of H. pylori infected primary gastric epithelial cells with T cells isolated from blood induced T cell apoptosis (H. pylori infection may cause the non-specific inhibition of circulating T cells, including tumor-specific T cells. In addition to H. pylori, several viruses, such as the hepatitis B virus, hepatitis C virus, human papillomavirus, and Epstein–Barr virus are also able to establish chronic infections in humans and increase host PD-1 or PD-L1 expression (An example of a chronic infection is c cancer . Previouas TNF-α –98. Das ne model . Furtherpoptosis . These rpression –94. Futupression –102. Sompression –108. If pression .As discussed, despite the clear benefits of PD-1 and PD-L1 blockade in treating some cancer patients, the efficacy and the recurrence of tumor are issues that remain to be tackled. Emerging evidence suggests that modulation of the gut microbiota is a promising approach for improving PD-L1 and PD-1 blockade therapy. However, future studies are needed to further develop this research area.Bifidobacterium species, particularly B. longum, increased anti-PD-L1 efficacy in mice models and was positively associated with anti-PD-1 efficacy in metastatic melanoma patients. Future studies are needed to understand the molecular mechanisms of these Bifidobacterium species in enhancing PD-1 and PD-L1 blockade therapy. In addition to the Bifidobacterium species, various studies reported positive associations of gut microbes with PD-1 and PD-L1 blockade therapy at genus level. These microbes need to be identified at species and strain level and their potential anti-tumor mechanisms require further investigation.The Several bacterial and viral pathogens are known to cause chronic human infections and the pro-inflammatory cytokines are known to induce host PD-1 and PD-L1 expression. In addition, some of these pathogens are known to directly attach immune cells. Whether chronic infections caused by different pathogens impact on PD-1 and PD-L1 blockade therapy should be investigated, and appropriate strategies to enhance PD-1 and PD-L1 blockade therapy in these patients can then be developed accordingly. A suggested course of action is outlined in Table Wrote the paper: YW, LZ. Figures and tables: YW. Revised the paper: YW, LZ, RM, FL, SL. All authors have approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Idiopathic Pulmonary Fibrosis (IPF) is a fatal fibrotic lung disease occurring predominantly in middle-aged and older adults. The traditional diagnostic classification of IPF is based on clinical, radiological, and histopathological features. However, the considerable heterogeneity in IPF presentation suggests that differences in gene expression profiles can help to characterize and distinguish disease severity.We used data-driven unsupervised clustering analysis, combined with a knowledge-based approach to identify and characterize IPF subgroups.Using transcriptional profiles on lung tissue from 131 patients with IPF/UIP and 12 non-diseased controls, we identified six subgroups of IPF that generally correlated with the disease severity and lung function decline. Network-informed clustering identified the most severe subgroup of IPF that was enriched with genes regulating inflammatory processes, blood pressure and branching morphogenesis of the lung. The differentially expressed genes in six subgroups of IPF compared to healthy control include transcripts of extracellular matrix, epithelial-mesenchymal cell cross-talk, calcium ion homeostasis, and oxygen transport. Further, we compiled differentially expressed gene signatures to identify unique gene clusters that can segregate IPF from normal, and severe from mild IPF. Additional validations of these signatures were carried out in three independent cohorts of IPF/UIP. Finally, using knowledge-based approaches, we identified several novel candidate genes which may also serve as potential biomarkers of IPF.Discovery of unique and redundant gene signatures for subgroups in IPF can be greatly facilitated through unsupervised clustering. Findings derived from such gene signatures may provide insights into pathogenesis of IPF and facilitate the development of clinically useful biomarkers.The online version of this article (10.1186/s12890-017-0472-9) contains supplementary material, which is available to authorized users. The clinical course of idiopathic pulmonary fibrosis (IPF), a chronic and fatal fibrotic lung disease, is highly variable. With a median survival of about 3 years, it ranges from a slow, steady loss of lung function over 5 or more years to a rapid progressive state and death within 1–3 years post-diagnosis. The typically slowly progressive course of IPF can be punctuated by intermittent episodes of precipitous decline in lung function termed acute exacerbation (AEIPF) , which oThe current approach in IPF diagnosis is limited to clinical assessment based on imaging and histology features. Stellar attempts, however, are currently underway to develop genomic signatures and blood-specific or lung-specific biomarkers in the future . Gene siWe postulated that data-driven and knowledge-based approaches using gene expression profiling of a large set of IPF/UIP cases would both allow us to identify novel patient subgroups with shared molecular characteristics and reveal novel candidate genes. Using transcriptional profiles on lung tissue from 131 patients with IPF/UIP and 12 non-diseased controls, we identified six sub-types of IPF that reflect disease severity. We have further identified molecular signatures that are capable of differentiating (a) IPF from normal controls and (b) severe from mild IPF. These signatures were subsequently validated in three independent cohorts of IPF/UIP. Finally, using knowledge-based approaches, we identified several novel candidate genes and potential biomarkers for IPF.http://www.lung-genomics.org; also deposited in data repository GEO - GSE47460 [LCO) were significantly lower in UIP/IPF patients compared to those of the control group. For evaluating the classifier performance and assessing the relevance of our identified IPF sub types, we used three independent IPF cohorts (GSE24206 [We used the microarray data from the IPF cohort in the Lung Genomics Research Consortium’s (LGRC) website (GSE47460 ). Among GSE24206 , GSE1066GSE24206  and GSE5LCO values among clusters. Following clustering, differential analysis was performed across IPF clusters and control with Benjamini–Hochberg false discovery rate (FDR) correction. Differentially expressed genes (DEG) were defined as those with FDR-adjusted p-value ≤0.05 and absolute log2 fold-change ≥1 when compared to control.We used the Scikit-learn  package We used the Scikit-learn package in Python to build and evaluate logistic regression classifiers to evaluate classification power of each IPF gene set. The datasets from the training and validation cohort were median normalized and scaled to  across each gene. In order to assess classifier accuracy and reduce over-fitting, we included a 2-fold cross-validation step before training the final classifier using all samples in the training cohort. Then, classifiers were used to predict IPF status in each validation cohort. Receiver-Operating-Characteristic (ROC) curve, overall accuracy, sensitivity and specificity were used to evaluate classifier performance.p-value ≤0.05. We used “known” IPF genes from the Orphanet [We used ToppFun of the ToppGene Suite  for funcOrphanet  and DisGOrphanet  databaseLCO measurements  and repeated the differential analysis comparing each of the phenotype-based UIP/IPF sub-groups with the control group. This resulted in 1175 and 1167 DEGs in IPF patients grouped by DLCO and FVC measurements, respectively. Surprisingly, we observed that even among UIP/IPF patients within the same FVC or DLCO sub group, expression of the genes was still highly variable , were arranged in descending order from patient clusters C6 to C1. DLCO values in patient clusters C5 orC6 were significantly lower than those in C1, C2, C3, or C4, and significantly higher in patient clusters C1 or C2 than those in C3, C4, C5, or C6. On the other hand, FVC and DLCO values did not differ significantly between C1 and C2, C3 and C4, or between C5 and C6   patients grouped based on FVC measurements . Three major gene expression modules (Gm) can be identified from the total 2968 DEGs. Gm1 was up-regulated in patient cluster C1, C3, C4, C6 and moderately in C5, Gm2 was up-regulated in patient cluster C1, C3, C5 and C6, while Gm3 was down-regulated in patient cluster C3, C5, C6 and moderately in C1 and C4. To gain functional insight into these genes, we performed enrichment analysis on them and found Gm1 was enriched in processes such as ‘extracellular matrix organization’, ‘regulation of cell migration’ and ‘collagen catabolic process’, Gm2 was enriched in processes such as ‘cilium’ and ‘cilium assembly’ and Gm3 was enriched in ‘angiogenesis’ and ‘lung alveolar morphology’. Taken together, these results show that UIP/IPF patient subgroups stratified by disease severity can be distinguished using gene expression profiles-based clustering, which in turn reveals the involvement of different molecular pathways in the pathogenesis and severity of fibrotic lung disease.Substantial differences in gene expression profiles were found between patient clusters that had similar disease severity, namely C1 vs. C2, C3 vs. C4 and C5 vs. C6 Fig. . Three ). All IPF subgroups shared a set of 145 DEGs, which were named the IPF core gene set. Among them, genes involved in ‘proteinaceous extracellular matrix’ and ‘regulation of epithelial to mesenchymal transition (EMT)’ were up-regulated, while hemoglobin genes such as HBA1, HBA2, HBD, HBG1 and HBQ1 were down-regulated . The most severe patient subgroups C5 andC6 shared DEGs in C1 and C3, which were enriched in processes including ‘mitotic nuclear division’, ‘cilium assembly’, ‘epithelial/endothelial migration’ and ‘tube development’. Patient clusters C5 andC6 also uniquely expressed 840 DEG, with 448 genes in C5 and 392 genes inC6. Subsets of C5 unique genes were enriched in pathways such as ‘cilium assembly’ and ‘tube development’, which were also perturbed in less-severe IPF subgroups C1 and C3. This suggests a potential IPF progression path of C1➔C3➔C5 characterized by increasing expression of cilium-associated genes, and is in consistent with a previous study that reported a positive correlation of cilium-associated gene expression and increased IPF severity [HMOX1, IL1R1, IL20RB, IL36G, SELE, SERPINF2, TNFRSF21 and TNFRSF6B, but not genes enriched in cilium-associated pathways . This suggests IPF can alternatively progress via up-regulating inflammation genes without further up-regulation of cilium-associated genes, and is consistent with a recent report showing increased inflammation in rapid progressive IPF [The number of DEG found in each of the patients’ clusters ranged from 262 genes (patient cluster C2) to 2117 genes (C5). About 34% of the total DEGs were unique to one patient subgroup while the remaining were found to be overlapping with the others Fig. . All IPseverity . TheC6-sTo further validate and assess the relevance of our identified IPF subgroups, we used three independent IPF cohorts . By utilizing multiple testing datasets, we determined if the gene sets reveal key differences in gene expression between IPF and normal, and between severe IPF (explant) and usual IPF (biopsy).. Specificity, sensitivity and accuracy in all three validation datasets were >90%. Similarly, we validated the C5 andC6 unique gene sets , but not severe disease (cluster average DLCO: <40%). Comparison of DEG from each patient cluster revealed additional gene signatures that robustly differentiated IPF from normal lung, and advanced IPF from usual IPF. Finally, using knowledge-based approaches, we identified several novel gene candidates and potential BALF biomarkers for IPF.In this study of patients with UIP/IPF, we stratified subgroups based on lung function measures and applied unsupervised analysis on gene expression data. Genes enriched in cilium or lung alveolar morphology were expressed at different levels in two distinct transcriptomic profiles from patient clusters with moderate disease  or grouped based on FVC (b) or DLCO (c). Differentially expressed genes were then extracted from each condition with FDR-adjusted P-value cut-off at 0.05 and fold-change cut-off at 2. Genes (rows) and samples (columns) were ordered using hierarchical clustering with Pearson correlation distance metric and complete linkage. (TIFF 1174 kb)Additional file 2:Figure S2. Principal Component analysis (PCA) plot characterized separation of IPF sample by three grouping methods. Distribution of IPF samples along the first two principal components derived from top 25% most variant genes are shown, and sample grouping were based on FVC (a), DLCO (b), or Ward clustering(C). Each point represents an IPF sample. (TIFF 282 kb)Additional file 3:Table S1. Comparison of FVC, FEV1, DLCO and age in six IPF patient subgroups. (XLSX 11 kb)Additional file 4:Table S2. List of all DEG compared with health control. (XLSX 339 kb)Additional file 5:Figure S3. Unsupervised clustering followed by differential analysis recovered almost all the DEG identified by other methods and discovered additional DEG. Comparison of differentially expressed gene identified based on different IPF patient grouping methods. Pooled-IPF, IPF patients were not divided into subgroups; FVC or DLCO grouping, IPF patients were divided into subgroups based on the FVC or DLCO categories, respectively; Clustering, IPF patients were divided into subgroups using PCA and Ward clustering. (TIFF 151 kb)Additional file 6:Figure S4. Heat maps of Core and advanced IPF gene set. 145 core IPF genes (a) and 392 advanced IPF genes were ordered using hierarchical clustering with Pearson correlation distance and complete linkage method. Patients (columns) were ordered in the same way in each heat map. (TIFF 770 kb)Additional file 7:Figure S5. The advanced IPF gene set could differentiate end-stage IPF but not AEIPF from usual IPF. Logistic regression models were trained on the advanced IPF gene sets using the training cohort, and tested using each validation cohort. The decision threshold was set to provide at least 90% sensitivity for IPF discovery. ROC curves were shown in the left column, and classification scatter plots of IPF and control samples were shown in the right column. (TIFF 163 kb)Additional file 8:Table S3. List of genes used as training set for ToppGene prioritization. (XLSX 20 kb)Additional file 9:Figure S6. Performance of Logistic Regression Classifier build on up to 50 top ranked putative BALF biomarkers. Putative BALF biomarkers were ranked based on the magnitude of their decision function coefficient derived from a logistic classifier trained using the training cohort. A series of logistic classifiers trained on up to 50 top ranked genes using the training cohort were tested using each validation cohort. The decision threshold was set to provide the highest prediction accuracy. (TIFF 78 kb)Additional file 10:Table S4. List of potential BALF biomarkers in the core IPF gene set. (XLSX 12 kb)


TDP-43 is involved in numerous RNA processing mechanisms including splicing. Over the last decade, ALS-causative mutations have also been found in other RBP-encoding genes, including FUS, MATR3, HNRNPA1, SFPQ and TIA1, sparking an interest in investigating RNA metabolism defects in ALS  and frontotemporal dementia (FTD) are two degenerative disorders with a strong clinical overlap; no effective cure is available for either , which has been implicated in aggregation of hnRNPs : A technique that uses an antibody against a specific RNA binding protein (RBP) to pull down RBP-RNA complexes, followed by high-throughput sequence analysis to analyse and precisely locate RBP binding sites on RNA.ENCODE (the encyclopedia of DNA elements): An international consortium that is aiming to map all the functional elements in the human genome by using a wide range of experimental approaches.LCD (low complexity domain): Protein stretches containing low amino acid sequence complexity. These are very common in hnRNPs and play a crucial role in their phase separation properties and in the assembly of stress granules.Stress granules: Cytoplasmic membrane-less bodies where, upon a variety of stress stimuli, mRNAs and proteins rapidly assemble. Translation is stalled in these granules, which disassemble after stress recovery.TARDBP levels are upregulated, due to loss of autoregulation (et al. show that TDP-43 loss of function leads to the hnRNP A1 protein becoming more cytoplasmic, with a concomitant reduction in nuclear levels in neurons from patients. It is intriguing to speculate that this may lead to an imbalance in HNRNPA1 autoregulation, thereby triggering the onset of a parallel HNRNPA1 vicious cycle (TDP-43 and hnRNP A1, like many other hnRNPs, are very tightly autoregulated through the binding of their own RNA in the nucleus, most likely because their functions are extremely dosage sensitive . When cyus cycle . TDP-43 et al. focuses on the link between TDP-43 and hnRNP A1, and highlights the fact that we do not know to what extent TDP-43 can influence other hnRNPs—an important question for further study. Recent reports suggest that an increase in levels of certain hnRNPs can rescue TDP-43 toxicity (et al. that TDP-43 changes can cause alterations in hnRNPs likely contributing to disease, an increase in hnRNP levels can, conversely, rescue TDP-43 toxicity. The mechanism by which hnRNPs rescue TDP-43 toxicity and whether such approaches can reverse the vicious cycles discussed above need further study, but the results clearly emphasize the complex interplay between hnRNPs in FTD and ALS.The manuscript by Deshaies et al. is that of hnRNP A1 cytoplasmic accumulations in ALS cases not carrying HNRNPA1 mutations. These accumulations appear in the same neurons where TDP-43 inclusions and nuclear depletion occur, consistent with the proposed role for TDP-43 loss in their formation, but intriguingly they do not co-localize with TDP-43 inclusions. Quantification of hnRNP A1B aggregates in different sporadic and familial FTD and ALS subtypes would help further confirm the relevance of this pathway to other forms of FTD and ALS. Reduction of hnRNP A1 in nuclei in the absence of cytoplasmic inclusions has been described previously (et al. of an hnRNP A1B-specific antibody may help to clarify how much cytoplasmic aggregation is driven specifically by the hnRNP A1B isoform.Accumulation of RBPs in ALS is typically seen in cases with mutations in these RBPs. Findings in non-mutant cases are less conclusive, although Matrin 3 accumulation has recently been described in sporadic ALS (et al. sheds new light on the hitherto less well studied hnRNP A1B isoform, which has an enlarged LCD that enhances aggregation and toxicity. This fits well with the hypothesis that LCDs contribute to the pathogenic fibrillization of RBPs involved in ALS (TDP-43, hnRNP A1 and the majority of RBPs involved in ALS share the presence of an LCD, which is important for their localization to stress granules, membrane-less organelles that assemble in the cytoplasm under stress conditions and which have been widely implicated in ALS pathogenesis. Indeed, the hallmark ALS inclusions have been proposed to derive from stress granules. The fact that hnRNP A1 and TDP-43 co-localize in stress granules, whereas they do not appear to do so in inclusions in patient neurons, is still compatible with this hypothesis. However, it may highlight a specific additional post-stress granule phase where aggregates of predominantly one RBP species are formed. The work of Deshaies


Graphene based room temperature flexible nanocomposites were prepared using epoxy thermosets for the first time. Flexible behavior was induced into the epoxy thermosets by introducing charge transfer complexes between functional groups within cross linked epoxy and room temperature ionic liquid ions. The graphene nanoplatelets were found to be highly dispersed in the epoxy matrix due to ionic liquid cation–π interactions. It was observed that incorporation of small amounts of graphene into the epoxy matrix significantly enhanced the mechanical properties of the epoxy. In particular, a 0.6 wt% addition increased the tensile strength and Young’s modulus by 125% and 21% respectively. The electrical resistance of nanocomposites was found to be increased with graphene loading indicating the level of self-organization between the ILs and the graphene sheets in the matrix of the composite. The graphene nanocomposites were flexible and behave like ductile thermoplastics at room temperature. This study demonstrates the use of ionic liquid as a compatible agent to induce flexibility in inherently brittle thermoset materials and improve the dispersion of graphene to create high performance nanocomposite materials. However, a major challenge in the fabrication of such flexible devices is the unavailability of suitable materials that combine high conductivity, mechanical flexibility and stability in electrochemical environments. Furthermore, most of the commonly used polymer matrices rapidly degrade at relatively low temperature3. The use of permanently cross-linked polymer structures such as epoxy thermosets could potentially offer high mechanical properties and stability4. They have high dimensional stability, high mechanical, thermal, and environmental resistance; and are therefore utilized in many challenging applications5.There has recently been great interest in making flexible/bendable electronics such as rollup displays and wearable devices with graphene based polymer composites typically being used as a flexible substrate7 based on addition-fragmentation chain transfer reactions in the presence of radicals9. However, such networks show limited reversibility and the chemical equilibrium can be displaced towards depolymerisation, leading to unfavorable network structure and performance10. Leibler et al. reported the synthesis of reversible epoxy networks based on exchange reactions that lead to thermoset materials with high levels of stress relaxation and recyclability11. This approach was further extended to other olefin containing polymers12.Thermoset epoxies are however highly brittle materials and thus offer no or limited flexibility. There are a few reports that focused on the formation of cross-linked networks that can disrupt and reform13. Here, ILs act as miscible molecular liquids to form charge transfer complexes with the epoxy and thus become part of the cross-linked network giving the materials distinctive thermo-mechanical properties14. Moreover, ILs are also known to possess excellent graphene dispersion capabilities15. Imidazolium based ILs have been used to make stable dispersions of reduced graphene oxide at relatively high concentration without using any surfactants/stabilizers. In this work, epoxy based flexible graphene nanocomposites were successfully prepared and characterized for their use in functional applications.Here we report an epoxy/graphene nanocomposite that is flexible and deformable after cross-linking and behaves like ductile thermoplastics. The flexibility was induced by the introduction of an imidazolium based room temperature ionic liquid. Structurally, ILs are molecular ions containing a bulky organic cation and a small anion® graphene nanoplatelets. The platelets have an average dimeter of 5 micron and a typical surface area of 120–150 m2.g−1. The epoxy precursor diglycidyl ether of bisphenol A (DGEBA) with an epoxide equivalent weight of 172–176 g.mol−1 and the curing agent 4,4′- methylenedianiline (MDA) were purchased from Aldrich Chemical Co. The ionic liquid 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]) was obtained from Fluka. The chemicals were used as received.Graphene nanoplatelets were obtained from XG Sciences commonly known as xGnP16 where it was observed that materials with high level of room temperature flexibility were only achieved at 40% of [BMIM][Cl] in epoxy. An IL content below 40% was found to be more ductile and rigid and at more than 40% of IL content the material started to loose stability and integrity. Epoxy mixtures containing 40 wt% IL were mechanically stirred for 1 hour. For the fabrication of epoxy composites pre-weighed amounts of nanoplatelets were first suspended in the epoxy [BMIM][Cl] mixture and then sonicated  for 1 hour. The resulting suspensions were mechanically stirred for 2 hours and then mixed with MDA. After complete dissolution of the MDA, the whole mixture was poured into pre-heated (100 °C) moulds, cured at 150 °C for 10 hours and then post-cured at 180 °C for 2 hours, with excess ILs were extracted out. Imidazolium based room temperature ILs possess high thermal stability. The decomposition temperature of BMIMCl is 291 °C. Hence the high temperature curing and post curing has no impact on the stability of IL or the nanocomposites.Epoxy resin containing all concentration of IL was studied in our previous research1. The q range was from 0.008 to 0.5 Å−1. An in-vacuum undulator source  at a beam energy of 9 keV was used. The exposure time for each sample was 2 s and tests were performed at 25 °C. The intensity profiles were interpreted from the plot of scattering intensity (I) as a function of scattering vector (q) which is related to the scattering angle θ by the relationship q = (4π/λ) sin (θ/2).The small angle x ray scattering (SAXS) beam-line at the Australian Synchrotron was used with a 1.6 m camera length to investigate the scattering patterns following a previously described procedureTg was taken as the maximum of the tan δ curve in the glass transition region.Dynamic mechanical tests were performed on a TA Q800 dynamic mechanical thermal analyzer (DMTA) operating in dual cantilever mode with a frequency of 1 Hz and a heating rate of 3 °C/min. The specimen dimensions were 60 mm × 12 mm × 3 mm. The storage modulus, loss modulus and tan δ were measured from 30 to 250 °C. The The tensile properties of the composites were measured on an Instron 30 kN SD tensile testing machine. The tests were conducted using dumb-bell shaped specimens according to ASTM standard D638. A minimum of five specimens were tested for each sample and the average values reported.Tg values were taken as the midpoint of the transition in the second scan of the DSC thermograms.DSC experiments were performed under a nitrogen gas atmosphere on a TA-DSC model Q200 instrument using 5–10 mg of each sample. The samples were first heated to and held at 100 °C for 5 min to remove the thermal history. The samples were cooled to −80 °C at a rate of 20 °C/min, held for 5 min, and finally heated from −80 to 250 °C at a rate of 20 °C/min (second scan). The The electrical resistivity of the samples was determined using an electrical resistivity cell with variable resistor and a distance between the electrode probes set at 1 cm. Prior to testing, the samples were polished for 30 seconds using 1200 grit paper at 150 RPM on a Struers Rotopol-1 polish machine .The morphologies of the nanocomposites were examined using a Zeiss Supra 55VP scanning electron microscope (SEM) operating at an accelerating voltage of 5 kV and a working distance of 10 mm. The cryo-fractured surfaces were coated with thin layers of gold to avoid charging.−1 using a Bruker RFS-100 FT-Raman spectrometer equipped with an Adlas Nd:YAG laser and a liquid nitrogen cooled Germanium diode detector. The samples were held on a mirrored backing in 180° backscatter geometry. Data acquisition, 256 scans, was performed using Bruker OPUS software (version 3.1). The laser power was 500 mW. A Blackman-Harris 3-term apodization function was used. Data manipulation was carried out using Grams AI software v9.1.Raman spectra were obtained at 1064 nm excitation and a resolution of 4 cm−1 and averaged over at least 4 scans, each with an accumulation time of 40 s. The Raman shifts were calibrated using the 520 cm−1 line of a silicon wafer. The spectral resolution was~1 cm−1. Data collection and manipulation was carried out using WiRE 4.2 software.Raman spectra were obtained at 514 and 785 nm excitation using an inVia confocal microscope system  through a x50 (0.75 na) objective. Incident laser powers were 0.8 mW (514 nm) and 2.3 mW (785 nm) and a coaxial backscatter geometry was employed. Spectra were collected over the range 100 to 3200 cm16. It has been reported that by varying the epoxy - ionic liquid ratio, materials could be produced that can exhibit distinct physical and mechanical characteristics ranging from those of brittle thermosets, to perfectly ductile thermoplastics, to elastomers. In the present work, a plastic-like thermoset composition was chosen to form the matrix for graphene nanocomposites. This matrix composition was prepared by using epoxy and the ionic liquid 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]) at a 60/40 (w/w) ratio. At room temperature, this cured thermoset composition can be bent and twisted by applying a relatively small force and the polymer retains the new shape even after the force is removed. The room temperature flexibility of these thermoset materials were explained by the confinement of ionic liquid molecules within the highly cross-linked thermoset and the charge triansfer complex formation between the components. Here, with a high ionic liquid content (40%), the bulky ions form a coupling between the epoxy cross links which break and reform when external forces are applied resulting in the flexibility of the material at room temperature.Thermal flexibility behavior can be induced in epoxy thermosets by introducing ionic liquid charge transfer complexes between functional groups within cross linked epoxy and ionic liquid ions17 and polymer nanocomposites18. The dispersion of individual CNTs and the curing of epoxy, both controlled by ionic liquids, were achieved in our laboratory19. In the present work, the combination of graphene platelets with ionic liquids leads to a high level of dispersion which was then utilized in making a particular type of room temperature flexible nanocomposites with improved properties. The graphene nanoplatelets were used “as received” without any purification or functionalization knowing that ionic liquids can uniformly disperse graphene. The high level of dispersion of the graphene nanoplatelets with the aid of the IL is clear from Fig. The non-covalent dispersion of carbon nanomaterials such as carbon nanotubes and graphene has been critical in the preparation of nanocomposites to increase the utilization of these materials while maintaining their inherent reinforcing and electronic properties. Ionic liquids have been investigated extensively in the past and found to be excellent non-covalent dispersing agents for carbon nanotubes (CNTs) in preparing bucky gels−1 (200 eV). This weak feature would be easily masked by the strong aromatic ring modes of the epoxy. While graphene is inactive and multiple layer of graphene absorb weakly in the infrared, both can be easily detected using Raman spectroscopy. Raman mapping with its high spatial resolution of 0.5 μm between analysis spots has potential to reveal the spatial distribution of the graphene within the epoxy matrix. While excellent Raman spectra were collected from the epoxy and epoxy/IL mixtures using both 785 and 1064 nm excitation, once the graphene was added no useful data could be obtained (not shown). Raman spectra of graphene are easily obtained using visible excitation. The epoxy was found to fluoresce, washing out all Raman spectral features, when 514 nm excitation was utilized (not shown).When a few layers of graphene are present, splitting of the G mode phonon makes it become active in the infrared spectrum near 1613 cm20.The distribution of graphene nanoplatelets in the epoxy/[BMIM][Cl] matrix was first examined using SEM. The SEM images of a graphene epoxy nanocomposite with a 0.6 wt% graphene loading shown in Fig. πα = 2.293%, where α = e2ћc 22. This means that over this spectral region each graphene layer absorbs 2.3% of the incident light. The optical absorption in graphene is dominated by interband transitions from the mid-infrared to the ultraviolet22. In this study, the absorption in the near infrared region (>0.8 eV) has been used to precisely determine the number of graphene layers present in sample comprised of 3 to 6 layers23.The composites were further analyses using Raman spectra (not shown). In the infrared-to-visible spectral range, the expected absorbance has been calculated to be independent of frequency and to have a magnitude given by 24. SAXS investigations of the nanocomposites were therefore performed to probe the degree of dispersion of the graphene within the reinforcing matrix. Interestingly, little difference in scattering signals can be observed, even at high graphene loading, over the q range investigated. The Lorentz plots (I(q)q2 vs q) shown in Fig. 25, and that the ILs provided a suitable platform to improve graphene dispersability26.Representative SAXS profiles in terms of intensity as a function of scattering vector q for different graphene loadings are presented in Fig. 27. It is apparent that graphene nanoplatelets can significantly enhance the mechanical properties of epoxy/ionic liquid flexible thermosets. This mechanical enhancement can be attributed to (i) high inherent elastic modulus and strength of graphene nanoplatelets (ii) better interactions between graphene and the epoxy/[BMIM][Cl] matrix and (iii) a more uniform graphene dispersion in the epoxy due to the presence of ionic liquid.Figure Tg of around 44 °C. The Tg of the flexible epoxy matrix remains about the same with the addition of graphene nanoplatelets and only decreases marginally (~3 °C) at higher (0.8 and above) graphene loading. In the previous research it was found that epoxy containing 40% IL become very soft when heated above Tg. Generally a reduction in Tg is attributed to either molecular chain confinement by the graphene sheets or the impact of the graphene sheets on the cross linking reactions of the epoxy4. In both cases, the polymer cross-link density decreases leading to an increase in polymer chain mobility.The thermal and thermo-mechanical properties of the nanocomposites were analyzed and the results are shown in Figs Tg of the epoxy remain more or less unchanged with the addition of graphene.The storage modulus of epoxy was found to improve with the addition of graphene Fig. . At room28. Such interactions would likely lead to a level of polarization of the structure, which was also experienced when testing the samples, as all the IL graphene composite materials exhibited a capacitor behavior by altering the charge propagation and overall surface charge of the bulk material at the graphene-epoxy interfaces29. The stabilization of the current across the samples was slow, and took up to a few minutes for the highest graphene loadings. The use of polymerizable ionic liquid crystals may offer opportunities to further reinforce such matrixes and generate epoxy resin materials into semi-conducting structures with various levels of electronic responses30.Interestingly, the electrical conductivity of the graphene IL composites was found to decrease with graphene loading content Fig. . The barThe graphene nanocomposites were all flexible at room temperature. The materials can be reversibly bent or twisted many times by applying a local force. Figure While commonly reported for thermoplastics, inducing flexibility into thermosets and fabricating bendable and foldable nanocomposite materials remains a great challenge. This is primarily due to the lack of suitable materials that combine both mechanical flexibility and superior conductivity for their high performance in electronic devices. Room temperature flexible nanocomposites were here prepared for the first time using epoxy and graphene nanoplatelets. An IL was used to induce network flexibility into a cross-linked epoxy thermoset resin. The IL also served as a functional dispersant for graphene nanoplatelets. A morphological investigation showed highly dispersed nanoplatelets in the matrix phase with the high level of dispersion attributable to the interaction between graphene and ionic liquid. The incorporation of graphene significantly improved the tensile mechanical properties of the epoxy with a huge 125% improvement in tensile strength. The storage modulus showed a 50% improvement at a 0.6 wt% graphene loading whereas the thermal properties of epoxy were not affected by the incorporation of the graphene. The nanocomposites and films show high levels of flexibility at room temperature where it almost behaved like a thermoplastic. It has been identified that the strong interaction between bulky IL ions and the epoxy hydroxyl groups link the brittle epoxy chains network. During physical deformation (or when heated), such secondary bonds reversibly break leading to flexible cross-linked networks. The electrochemical properties have to be further investigated to explore the potential of these materials in flexible electronic devices.


Cylindrical silk fiber (SF) was coated with Graphene oxide (GO) for capacitive humidity sensor applications. Negatively charged GO in the solution was attracted to the positively charged SF surface via electrostatic force without any help from adhesive intermediates. The magnitude of the positively charged SF surface was controlled through the static electricity charges created on the SF surface. The GO coating ability on the SF improved as the SF’s positive charge increased. The GO-coated SFs at various conditions were characterized using an optical microscope, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and LCR meter. Unlike the intact SF, the GO-coated SF showed clear response-recovery behavior and well-behaved repeatability when it was exposed to 20% relative humidity (RH) and 90% RH alternatively in a capacitive mode. This approach allows humidity sensors to take advantage of GO’s excellent sensing properties and SF’s flexibility, expediting the production of flexible, low power consumption devices at relatively low costs. The onset of the internet of things (IoT) and virtual reality (VR) demands the development of flexible, portable devices ,2. TheseIn fact, several approaches have been investigated for this purpose via implementing adhesive intermediates between GO and selected objects for better adhesion ,31,32 MeGO, dispersed with a concentration of 0.1 wt % (1 mg/mL) in DI water, is negatively charged due to the oxygen functional group attached to the GO. In contrast, an SF surface tends to be positively charged due to static electricity. The static electricity occurs due to an electrical charge imbalance on the SF surface, which has a high electrical resistance to the charged carrier. The magnitude of the static electric force on the SF surface varies depending on the tendency of the electrons to move from the SF to another material when the SF contacts and separates from that material . −1 from the SL, the presence of GO was set at 1, and the absence of GO was set at 0. The Raman mapping results show that high quality GO was uniformly and seamlessly coated on the SL rubbed against the latex glove, while the GO was lightly coated on the SG rubbed against the glass bar. This clearly indicates that the surface of the SF rubbed against the latex became more positively charged than that rubbed against any other materials in this work. By extension, this SF surface attracted more GO. In addition, the Raman analysis clearly distinguished the SA and SL, as shown in The uniformity and quality of the GO coating on the SF were further investigated via a Raman analysis. No peaks were observed from the SW, but the peaks representing the GO began to be observed and were fully observed from the SA and SL, respectively, as shown in The electrical properties of the GO-coated SF (SL) was further investigated at various coating times, as shown in 2O. The humidity in the air was quantified via the capacitance as shown in Finally, the SLs were implemented as an active sensing material between two Cu plates for capacitive humidity sensor applications, as shown in In summary, flexible silk fiber (SF) was coated with graphene oxide (GO) via electrostatic force without adhesive intermediates. It was found that the electrostatic force, i.e., the adhesion force, between the GO and SF could be controlled. The GO was uniformly and seamlessly coated on the SF in a large area, which was characterized by optical image, secondary electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and a Raman analysis. In addition, the electrical properties of the GO-coated SF were investigated as a function of coating time and temperature. The GO-coated SF showed the feasibility of capacitive humidity sensor, unlike the intact SF. This approach allows the humidity sensor to take advantage of GO’s excellent sensing properties and flexibility. Therefore, it is expected that this method will enable the production of flexible, low power consumption devices at relatively low costs.