Nanocarbon-based materials, such as carbon nanotubes (CNTs) and graphene have been attached much attention by scientific and industrial community. As two representative nanocarbon materials, one-dimensional CNTs and two-dimensional graphene both possess remarkable mechanical properties. In the past years, a large amount of work have been done by using CNTs or graphene as building blocks for constructing novel, macroscopic, mechanically strong fibrous materials. In this review, we summarize the assembly approaches of CNT-based fibers and graphene-based fibers in chronological order, respectively. The mechanical performances of these fibrous materials are compared, and the critical influences on the mechanical properties are discussed. Personal perspectives on the fabrication methods of CNT- and graphene-based fibers are further presented. E), unparalleled thermal and electricity conductivity, and ultrahigh electron mobilities [σ) and E are widely used in aerospace, aviation, automobile, electronic, mechanical, chemical, textile, and other civilian industry. However, the electrical and thermal conductivities of carbon fibers are not satisfied. One-dimensional (1D) macroscopic architecture of CNTs and graphene, namely CNTs fibers (CFs) and graphene fibers (GFs), are analogous to carbon fibers in constitution and structure. Moreover, the combined performances including good flexibility and excellent electrical and thermal conductivities make them potential as structural–functional integrated materials. As more attentions have been attracted to the macroscopic fibers of 1D CNTs and 2D  graphene, it is the time to give a correlative review about CFs and GFs together. We think that this insightful review can help researchers to have a better systematic understanding of the whole developing journey of macroscopic assembled fibers. In this mini review, we firstly introduce the assembly strategies of CFs and GFs and then compare the mechanical performance of fibers made from different approaches. Finally, we present our perspectives on the future of CFs and GFs.Nanocarbon-based materials, such as carbon nanotubes (CNTs) and graphene, are extensively investigated due to their outstanding properties such as large theoretical specific area, high Young’s modulus  if they can attain the extraordinary mechanical and electrical properties of individual CNTs. This requires that the CNTs in the fibers are sufficiently long, highly aligned, and packed in an arrangement, and is nearly free of defects. Until now, the strategies for assembling CNTs to CFs can be classified into liquid- or solid-state spinning approaches. Liquid-state spinning approaches involve the dispersing of CNTs in a suitable solvent and shaping in coagulation bath. Solid-state spinning approach circumvents the dissolution problem either by drawing a fiber from a vertically grown CNT array or by drawing directly from an aerogel in the furnace .Liquid-state spinning approaches generally include polymer-based coagulation spinning method, liquid crystalline (LC) spinning method, polymer-free spinning method, and dip-coating method. Among them, polymer-based coagulation spinning method is first introduced to achieve CFs.σ and 15 GPa for E [The history of CFs fabrication dates back as far as 17 years ago. In 2000, Poulin’s group dispersed single-wall carbon nanotubes (SWNTs) in sodium dodecyl sulfonate (SDS) solutions, recondensed the nanotubes in the flow of poly (PVA) solution to form a nanotube mesh, and then collated this mesh to a nanotube fiber  [By utilizing SWNTs synthesized from carbon monoxide and lithium dodecyl sulfate as a surfactant, Baughman’s groups first produced mechanically strong gel fibers. After post-treatment with acetone-washing bath, continuous, multifunctional dry CFs were achieved. The resultant CFs showed a dramatically increased 0 J g−1) , 10 Besi0 J g−1) . The res0 J g−1) .The main challenge of producing CFs is to disperse the CNTs at high concentration for efficient alignment. Using surfactant is an effective approach to disperse CNTs into solutions, yet there is a loss in the properties of CFs due to the decreased van der Waals interaction between the neighboring CNTs. So super-acid (100% sulfuric acid) was introduced to increase the dispersity of CNTs. The protonated SWNTs in the super-acid behave as rigid-rod-like liquid crystals (LC) and exhibit an isotropic-to-nematic phase transition with an increased concentration Fig. a, b 12––12–14. BE and 116 MPa for σ) and electrical (5000 S cm−1) properties.Ericson et al.  improved−1) of these fibers were two orders of magnitude higher than that of fibers made by polymer-based coagulation spinning method (0.2 S cm−1).Unlike the LC spinning method, polymer-free spinning process using dilute, low-viscosity CNT dispersions (0.6 wt%) as spinning dope. By adjusting the pH (pH > 13 or pH < 1), polymer-free, surfactant-stabilized CNTs were flocculated/coagulated rapidly and uniformly to afford continuous CNTs gel fibers  can yield LC phase due to its high aspect ratio (or width/thickness ratio) and sufficient dispersibility/solubility with the solution concentration up to 30 mg mL−1 –49. This−1 . The gelpacitors , 51.Fig.−1 were also be spun by Yu’s group. They injected GO dispersion into CATB solution, and the curliness-fold formation mechanism of GO fibers was proved by SEM observations  and poly (glycidyl methacrylate) (PGMA) chains were covalently and uniformly grafted onto GO surfaces via a simple free radical polymerization process , 58. Theσ = 652 MPa, E = 20.9 GPa). A deformation mechanism model was also proposed based on the SEM observation  approach and wet-spinning technology to continuously fabricate biomimetic composites fibers Fig. a–g. Theyion Fig. h–j. Besiion Fig. k–m, reacanowires , bismuthanowires  and mont2 and was hold by glass slides for drying in air [3O4 and TiO2 and obtained functional GFs with magnetic and photoelectric  response [3O4 functionalized GFs was then acted as both substrate and catalyst for CVD growth of CNTs. The subsequent 1D CNTs and 2D graphene hybrid fibers with a large surface area (ca. 79.5 m2 g−1) and high electrical conductivity (1200 S m−1) were achieved [Besides the above wet-spinning method, Qu’s group developed a one-step dimensionally confined hydrothermal strategy to prepared GFs . They ing in air . To endoresponse . The Fe3achieved . This stachieved .Reduced GO nanoribbon (GONR) fibers were also fabricated by using an electrophoretic self-assembly method without any polymer or surfactant. Specifically, a graphitic tip as a positive electrode was immersed into the chemically reduced GONR colloidal solution in a Teflon vessel containing the counter electrode. The distance between two electrodes is ca. 5 mm, and the fiber is drawn out under a constant voltage ranging from 1 to 2 V. After annealing treatment, the fiber showed superior field emission performance with a low potential for field emission and a giant field emission current density when compared with vertically aligned few-layer graphene and single-layer graphene films prepared by electrophoretic deposition .Different from the above three methods using GO as precursors, self-assembly method directly utilizes graphene films to fabricate GFs. The 1D fiber-like structures were self-assembled from 2D graphene films in an organic solvent  and then dried to give the porous and crumpled structure , 71. Theσ and 1.25 to 397 GPa for E , it is fundamentally important to probe the critical factors affecting the mechanical properties of CFs. The CNT structures  [σ and E would reduce with increasing twisting MWNT fibers to a larger extent [Based on the assembly approaches, the mechanical properties of CFs show a broad range from 109 to 8800 MPa for ntation)  and CF gntation) . The larr extent .Table 1SE of CFs. To solve this problem, strong interaction between the tubes must be introduced. Electron beam irradiation is an effective approach to cause stable links between neighboring CNT within bundles. The mechanical properties showed a 30-fold increase in the bending modulus due to the formation of stable crosslinks that effectively eliminate sliding between the nanotubes [Owing to the weak van der Waals interaction between the neighboring CNT, the CNT can easily slide on each other, resulting in a low anotubes .−1, far superior to commercially used high-strength fibers [−1, far exceeding spider dragline silk (165 J g−1) and Kevlar (78 J g−1) [Besides the electron-beam-induced crosslinking approach, a method based on filtration-twisting was proposed to fabricate CNT-based composite fibers . The strh fibers . Further8 J g−1) .σ from 0.55 to 0.91 GPa compared with the pure fibers. After crosslinking at 120 °C for 2 h, σ and E of the fibers increased to 2.2 GP and 120 GPa, respectively  [σ is raised from 124 to 214 MPa and E reaches 47 from 14 GPa. To decreasing the structural defects, large-sized GO were used as building block [σ ranged from 214 to 501 MPa. To enhance the interlayer interaction, PVA [σ of 199, 652, 452, and 500 MPa, E of 17.1, 20.9, 8.31, and 18.8 GPa, respectively (as shown in Table The first GFs show a ht knots . Compare1.1 TPa) –83, a pl1.1 TPa) , 85. The1.1 TPa) . When drng block , 86, 87.ion, PVA , HPG [59ion, PVA , PGMA [5ion, PVA , and SA ion, PVA  were intσ break through 1 GPa for the first time. In 2015, Lian’s group improved the mechanical performance of GFs to 1.15 GPa by combining the large-sized graphene with small-sized graphene, aided by flowing-stretching and high-temperature graphitization treatment [High-temperature graphitization process is a more effective method to achieve high-performance GFs since the structural defects were removed or restored. The reatment . Recentlreatment –91.Many methods are developed to assemble CNTs and graphene into macroscopic fibers. For CNT fibers, on account of the entanglement nature between individual nanotubes, the approach of drawing CNT out from superaligned CNT arrays or aerogels is promising in achieved continuous, high-strength and high-electrical-conductive fibers. For GFs, considering the excellent dispersity of GO in water and organic solvent, liquid-state spinning approaches may be more competitive in the future.σ of CFs and GFs both exceed 1 GPa, comparable to that of the universal carbon fibers. In order to improve the performance of macroscopic CFs and GFs, defects such as voids and disordered orientation should be minimized.Although great progress has been made to improve the mechanical performance of macroscopic CFs and GFs, a wide gap still exists considering the intrinsic properties of CNT and graphene building blocks. Until now, the To further upgrade the combined performance of CFs and GFs, especially the mechanical strength and electrical conductivity, much work is waiting to be explored and more sophisticated understandings about the relationship between the structure and performance is of significant important from the viewpoints of both fundamental research and real application. On the one hand, we should establish a real-time system to monitor the structural evolution of the basic CNTs/graphene units during the fiber-forming process, which will contribute to the structure controlling of the fibers. On the other hand, the processing techniques  used to enhance the performance of polymeric fibers and carbon fibers should be borrowed to optimize the fabrication process throughout.


X-ray photoelectron spectroscopy (XPS) revealed the relative extension of the graphene sheets π-system and the type of nitrogen chemical functions present in the lattice structure. Scanning Electron microscopy (SEM), Transmission Electron microscopy (TEM) and Raman spectroscopy were applied to determine morphological and structural characteristics of the sheets. Optical emission and FT-IR spectroscopy were applied for characterization of the high-energy density plasma environment and outlet gas stream. Electrochemical measurements were also performed to elucidate the electrochemical behavior of NG for supercapacitor applications.Direct assembling of N-graphene, i.e. nitrogen doped graphene, in a controllable manner was achieved using microwave plasmas at atmospheric pressure conditions. The synthesis is accomplished via a single step using ethanol and ammonia as carbon and nitrogen precursors. Tailoring of the high-energy density plasma environment results in a selective synthesis of N-graphene (~0.4% doping level) in a narrow range of externally controlled operational conditions, i.e. precursor and background gas fluxes, plasma reactor design and microwave power. Applying infrared (IR) and ultraviolet (UV) irradiation to the flow of free-standing sheets in the post-plasma zone carries out changes in the percentage of sp Among the possible doping agents, nitrogen has drawn a considerable amount of attention because its atomic radius is comparable to that of carbon and contains five valence electrons available to form strong covalent bonds. The conjugation between the nitrogen lone-pair electrons and the graphene π-system modifies graphene physical and chemical properties. The substitution of carbon atoms by nitrogen ones influences the atomic charge distribution on the graphene scaffold and creates “active sites” thus significantly increasing the electrochemical activity of nitrogen-doped graphene, known as N-graphene (NG)4.Beyond its unique set of physico-chemical properties, graphene can be considered as a robust, atomic scale scaffold from which other 2D materials can be derived through the attachment of foreign atoms and functional groups5 predicted modified electronic and chemical properties of nitrogen-doped graphene, which is being supported by numerous experimental investigations. Indeed, there is significant experimental evidence of the advanced properties of the NG-based materials in respect to already practically implemented ones5. For instance, NG has been tested in fuel cells either as the catalyst or carbon supports. The “active sites” can be engaged in catalytic reactions, such as oxygen reduction reaction (ORR), or can be used as a scaffold for other catalysts8. NG demonstrates better chemical reactivity and sheet-to-sheet separation than the pristine graphene9. To this end, N-doping is a very promising approach for the development of metal-free carbon-based catalysts with even better performance than commercially available Pt-based electrodes, with prospective impact on fuel cells’ commercialisation. However, the lack of an appropriate synthesis route providing both high quality and quantity of NG hinders its practical implementation.The theoretical studies5. The influence of the N-bonding configuration on the carrier concentration and consequently on the electronic properties of graphene was studied in10.Graphitic, pyridinic and pyrrolic are the three common N-bonding configurations. Graphitic N can facilitate electron transfer by lowering charge-transfer resistance of the electrode. Being electrochemically active, pyridinic and pyrrolic N offer high pseudocapacitance−1), excellent life number of cycles , suitable to operate with flexible substrates and various electrolytes were developed in11 using nitrogen-doped graphene. Moreover, N-doped graphene has been hybridized with different metal compounds to enhance electronic and ionic conductivity12.N-doped graphene display interesting properties for charge storage applications. Supercapacitors with high capacitance , spintronics, etc.26. The sensing ability of NG was investigated for certain dyes by a new surface analysis technique, i.e. graphene-enhanced Raman scattering15. It was demonstrated that NG can be used to efficiently detect trace amounts of certain molecules.N-doped graphene nanoribbons were also tested as conductive host materials in lithium-sulfur (Li-S) batteries, demonstrating stronger fixation of sulfur-containing species and higher stability, as compared with pristine graphene nanoribbons27. The battery exhibited an open-circuit voltage of 1.46 V, a specific capacity of 873 mAhg−1, and a peak power density of 65 mWcm−2, that can be continuously charged-discharged with an excellent cycling stability.Rechargeable zinc-air battery with the nitrogen-doped graphene nanoribbons used as an air electrode in a two-electrode configuration was assembled in5 can be categorized into in-situ direct methods and post-treatment approaches. In situ approaches characterized by simultaneous graphene synthesis and N-doping include CVD, ball milling, solvothermal synthesis, etc19 CVD involves growth of N-graphene on a preheated structure  in the carbon and nitrogen-containing environment. Although CVD is one of the most common methods for in-situ NG synthesis, it suffers from metal interference. Post-treatment methods include wet chemical methods, thermal annealing of graphene oxides (GO) with heteroatom precursors and plasma-based treatments38. These methods present several drawbacks, such as degradation of the nanostructure properties due to the transition metals used, the requirement of expensive and/or hazardous catalysts, vacuum systems and very high temperatures, and lengthy/complex batch procedures. Although, in principle, direct synthesis may have the potential to create homogeneous doping throughout the bulk material, the results reported up to now fail to indicate so. As a rule, graphene oxide (GO), in the presence of N-precursors, has been frequently used for N-graphene synthesis. However, chemical reduction of GO requires the use of reducing toxic agents. Although it is a low-cost method to produce N-graphene in a relatively large scale, the materials obtained exhibit only relatively low electrical conductivity due to the contaminants, saturated sp3 bonds and bonded oxygen groups30. Thus, restoration of the high conductivity of N-graphene sheets is an issue.Numerous methods for synthesis of N-graphenehttps://graphene-supermarket.com/) show variable physical properties, thus limiting their use. Generally, the fabrication of N-graphene meets significant unresolved problems such as: i) uncontrolled N bonding type and distribution; ii) N doping at non-specific positions and untuned doping content. Most importantly, the greatest challenge on the path towards either graphene or N-graphene commercialization is the controllable production of high quality material on a large scale, at low cost and in a reproducible manner. To this end, plasmas and their ability to control energy and matter at an atomic scale level appear as powerful tools to tackle this challenge3. Plasma assisted growth of nanostructures can be achieved without the use of catalysts due to plasma’s unique ability to activate the surface, thus creating favorable conditions for nucleation and growth processes.Graphene/N-graphene´s properties vary strongly as a function of its synthesis method and their intrinsic properties are drastically dependent on the structural quality. A good spatial control of the energy and mater fluxes at a nanoscale, is indispensable in enabling a cost-effective and environmentally friendly synthesis process and constitutes one of the main challenges of the above-mentioned conventional methods. Existing commercial products  was achieved using low pressure RF nitrogen plasma treatment39. Similarly, microwave N2-Ar post discharge plasma was used for N-doping of free-standing graphene, with a maximum level of doping achieved of 5.6%32. Gas-phase controllable doping of graphene by ammonia plasma exposure, with maximum doping level of about 0.4% has been reported in32. However, the large percentage of oxygen, common for post-treatment approaches, is to be noticed. Generally, plasma-based post-treatment approaches can provide higher levels of N-doping compared to direct ones, but these processes have some disadvantages. They are two-step processes, slower, more complex and expensive, and are commonly performed at low-pressure conditions. Furthermore, plasma post-treatment affects only the surface of the sample, which significantly reduces its effectiveness.The successful synthesis of N-graphene consisting of multiple layers with 1% level of doping using a DC arc-discharge with carbon electrodes in an atmosphere of ammonia, was reported inin-situ direct synthesis of free-standing N-graphene flakes at a relatively high yield (~ 1.3 mg min−1), was achieved in a single step by employing microwave plasma  operating at atmospheric pressure conditions44. An ethanolic solution of ammonia (4 wt %) was used as precursor of both carbon and nitrogen. Argon was used as a background gas. The plasma properties have been tailored to achieve selective synthesis of free-standing N-graphene sheets. The flowing sheets were submitted to UV and IR irradiation in the post-plasma zone during their flight to the collecting system to further improve their structural quality40. Raman spectroscopy, SEM and TEM and XPS were used to characterize the morphology, microstructure and chemical properties of the synthesized material. The outlet gas stream was analyzed by Fourier-Transform Infrared spectroscopy (FT-IR) to detect the generated by-products. The electrical conductivity of the synthesized NG samples was determined using the Van der Pauw method45. Electrochemical measurements were also performed to elucidate the electrochemical behavior of NG for supercapacitor applications. Optical emission spectroscopy (OES) was used to detect the emission of plasma generated “building units” and to determine the gas temperature.In the present work, 2, C, CN, N) and to determine important plasma parameters such as the gas temperature in the “hot” zone of the plasma reactor, emission spectroscopy has been applied. Optical emission spectroscopy allows the identification of the active carbon/nitrogen species in the plasma that are the “building units” for the synthesis and growth of the nanostructures in the mild plasma zone43. The detected argon/ethanol/ammonia plasma emission spectra in the visible range (240–750 nm) are shown in Fig. 2Σ → X2Σ), C2 , CH band, the hydrogen Balmer-alpha line Hα (656.3 nm) and several Ar lines. These species are formed as a result of ethanol/ammonia decomposition and intensified chemistry in the “hot” plasma zone. As it can be seen in Fig. 2 molecular band, i.e. the Swan system, with heads band at 473.7, 516.5 and 558.6 nm were detected. The typical green colour of the plasma  is due to C2 emission caused by the radiative decay of the excited state C2*(A3Πg). Electron impact and three body recombination processes, involving carbon and argon atoms, are responsible for the excitation of the ground state C2 molecules to the C2*(A3Πg) excited state, while CN species are formed according to the reaction C + N + Ar → CN*(B2Σ) + Ar44.To identify the species of interest  (3000–3200 Å) band was used to estimate the rotational temperature, which at atmospheric pressure conditions is nearly equal to the gas temperature. The OH spectrum detected in the range 307.5–315 nm,  at axial distance z = 2.5 cm from the launcher in the “hot” plasma domain is shown on Fig. 44. An exemplification of the 2D map of the temperature as obtained by an infrared-sensitive thermal imager (FLIR camera) is shown in Fig. 40 can be clearly distinguished. The temperature corresponding to the position of the marker is 437 °C.The gas temperature in the plasma, particularly in the “hot” zone, is an essential parameter regarding plasma kinetics. In gas discharges, the gas temperature can be usually assumed equal to the rotational temperature of diatomic molecular species−1 and 1000 cm−1, which are “fingerprints” of the ethanol and the ammonia molecules, respectively. With the plasma turned on, these lines are not present, clearly indicating that the ethanol and ammonia molecules are decomposed in the plasma environment. At the same time, the absorption peaks of CO at around 2170 cm−1; C2H2 and/or HCN at around 720 and 3300 cm−1, and C2H2 at around 1350 cm−1 are detected  of the 2D peak in the synthesized samples is typically 50 cm−1, suggesting that graphene dominantly consists of several layers. For the sample obtained without application of IR and UV irradiations, the intensity ratio of the D-band to G-band at different locations on the sample vary significantly, as seen from Fig. As seen from the figures the spectra are dominated by three peaks, attributed to the D, G and 2D bands at about ~1332 cmEx-situ XPS analysis has been performed to study the relative extension of the delocalized system, the amount and type of nitrogen atoms doping the graphene and the amount of oxygen.40. However, N 1s spectrum shown in Fig. 52 and/or nitrogen atoms bound to oxygen, like nitroso groups.Nitrogen was detected in all the samples. The detailed XPS regions Fig.  show dif2 carbon atoms in highly delocalized C-C bonds, and the expected features due to the energy losses associated to π-π* excitations. This energy losses region can extend roughly from 287 eV to over 295 eV, superposing to much less intense photoelectron peaks assigned to carbon bound to oxygen , which, as attested by O 1s region (not shown), is in a residual amount  and also has the largest relative amount of nitrogen (N/C ~ 0.4%) and is the least oxidized (O/C = 1.5%). The sequence of UV irradiation and relatively low heating (i.e. 200 °C) slightly increases the sp2%. Additionally, changes in the relative amount of the different nitrogen groups are observed, such as an increase of the amounts of pyridinic and pyrrolic nitrogen. This might be caused by activation of the defects due to additional heating, with the subsequent bonds reorganization. The fact that these changes are small, however, makes it difficult to assess the validity of this assumption and further investigation to analyze this influence is an ongoing work. The small decrease of oxygen/carbon ratio from 0.021 to 0.015 can be attributed to the kicking-out of the oxygen groups by UV irradiation with a photon energy of ~3 eV.The results in Table The electrical conductivity of the N-graphene sheets was measured on pressed disc pellets of 8 mm diameter and thickness between 1.2 and 3.2 mm. A four-contact configuration with pinching point contacts located on the periphery of the pellet, was used, providing longitudinal conductivity measurements for the current lines parallel to the pellet surface. For the current ranging from 0.5 to 3.5 mA, the current-voltage characteristics and reconfirmation of the Ohmic contact character were obtained.54.The values of electrical conductivity presented in Table QAr = 1200 sccm, QAr/Et/Am = 120 sccm and submitted to IR and UV irradiation, was tested as electrode for supercapacitor applications by performing cyclic voltammetry (CV), galvanostatic charge-discharge (GCD) and Electrochemical Impedance Spectroscopy (EIS) in 1 M H2SO4 electrolyte. The measurements were performed in a three-electrode electrochemical cell using Pt and Standard Calomel Electrode (SCE) as counter and reference electrodes, respectively.N-graphene, produced at P = 2 kW, vs. SCE at varying scan rates, are presented in Fig. −1. Such rectangular features and high reversibility can be attributed to the high and easily accessible active surface area of the N-graphene.The CV curves obtained in the potential window of 0–0.8 V −1 , ∆t is discharge time (s), and ∆V is working potential window. The specific capacitance of 8.87 Fg−1 was obtained at current density of 0.1 Ag−1 which retained ~100% of the capacitance on increasing the applied current ten times higher i.e. at 1 Ag−1  to study the resistive nature of the synthesized N-graphene. The spectra along with the equivalent circuit proposed to fit the data are illustrated in Fig. 2 obtained from fitting suggest negligible charge transfer resistance.Nyquist plot gives the information about the charge transfer resistance at high frequency and capacitive at low frequency. The absence of a semi-circle in the high frequency region, as can be noticed from magnified plot shown in inset of Fig. o in the mid frequency region represents the diffusion of ions dependent on frequency. A well-defined and short Warburg region portion, with phase angle of around - 45° (n = 0.51), evidences the short and equal diffusion path length of the ions in the electrolyte. Also, the Warburg resistance value of 0.386 Ωcm2 was very low. The very low charge transfer resistance and the decreased diffusion effect can be the reason for very fast reversible processes at the interface, which explains the rectangular CV, the rectangular nature retention even at high scan rates and the linear profiles of GCD plots. At very low frequency, the presence of almost vertical line and phase angle close to - 90°  and ultraviolet (UV) irradiation to the flow of free-standing sheets in the post-plasma zone carries out changes in the percentage of spElectrodes assembled with the produced N-graphene showed good electrochemical response with negligible interfacial resistance, even at low percentage of N-doping in the graphene, evidencing high potential for supercapacitor applications.By optimizing the microwave plasma reactor performance, along with detailed modelling of the plasma environment and formation of the main “building units”, well controlled synthesis of carbon/nitrogen atom lattices can be generated. Further investigations are underway in these directions, including the use of other carbon/nitrogen precursors such as methane, air, pyridine etc., to achieve further advancements in this technique, and increase the yield along with reduction of the cost via scaling-up the plasma reactor. Focus will be on mastering the process by achieving control on both the level of doping and bond configuration.The method is highly scalable and versatile: carbon precursors in liquid, gas and solid state can be used and different graphene derivatives can be synthesized using the same plasma reactor. Moreover, customization is possible, i.e., depending on the target application one can tailor N-graphene sheets in a suitable form and required quality.Supplementary Material


The real capacity of graphene and the lithium-storage process in graphite are two currently perplexing problems in the field of lithium ion batteries. Here we demonstrate a three-dimensional bilayer graphene foam with few defects and a predominant Bernal stacking configuration, and systematically investigate its lithium-storage capacity, process, kinetics, and resistances. We clarify that lithium atoms can be stored only in the graphene interlayer and propose the first ever planar lithium-intercalation model for graphenic carbons. Corroborated by theoretical calculations, various physiochemical characterizations of the staged lithium bilayer graphene products further reveal the regular lithium-intercalation phenomena and thus fully illustrate this elementary lithium storage pattern of two-dimension. These findings not only make the commercial graphite the first electrode with clear lithium-storage process, but also guide the development of graphene materials in lithium ion batteries. The mechanism of lithium storage in graphenic carbon remains a fundamental question to be addressed. Here the authors employ suitable bilayer graphene foam to investigate various physiochemical phenomena of lithium intercalation and propose a storage model. Before its commercial application in 19902, intensive studies had been performed to determine its related Li-storage process/mechanism4. Examples include the classical pleated-layer model by Daumas and Hérold in 1969, and the earlier Rüdorff model in 19657. Recently, in the wake of the discovery and development of graphene  and the numerous reports of enhanced energy-storage performances of graphene-modified electrode materials, many researchers believe that the capacity of LIB can be significantly enhanced through simply replacing the traditional graphite anode by this ultimate carbon material that has metal-level conductivity, large surface area (2630 m2 g−1 in theory), and possibly two exposed sides to adsorb Li atoms (namely forming the expected Li2C6 stoichiometry with a doubled capacity of 744 mAh g−1)10. However, despite the considerable investment in money and time, this target has not been achieved by using pure graphene materials. Even the Li-storage mechanism (or the storage locations) on graphene is still up for debate both experimentally and theoretically12. For instance, based on density functional theory (DFT) calculations14 and the different electrochemical behavior of monolayer graphene supported by Cu foil from those of multilayer graphenes/graphite for LIBs15, it has been proposed that Li atoms cannot be adsorbed onto pristine monolayer graphene, instead they only intercalate into the graphene interlayer or the interspace between graphene and substrate through edge planes or high-order defects . The understanding and resolution of this problem are rather essential for the development of graphene materials in LIBs.Despite its limited capacity (maximum of 372 mAh gn) into account, the considerable difference between the deduced theoretical capacities assuming the above opposite viewpoints . However, basic requirements for graphene in LIBs, such as a sufficient monolithic mass and absence of extrinsic interference from the as-applied substrates  to address this issue.Taking the number of graphene sheet layers  route17 Fig. , we have17 Fig. . Such a 17  was measured to be about 0.49, in good agreement with the computational and experimental values of I{0110}/I{1210} ≈ 0.4–0.5 for the Bernal (AB) stacking bilayer graphene23. By distinguishing the height, width, Lorentzian fits, intensity, and chemical-shift features of the 2D and G bands, Raman spectroscopy can provide more definitive identification for graphene materials with diverse numbers of layers regardless of the macroscopic appearance27, as displayed in Fig. 8 C6-ring units with an area of 0.052 nm2) were randomly collected from different locations on the surface and cross-section of the as-prepared samples (before and after removing the Ni substrate). In this way, the bilayer-dominated region in our target material was estimated to be over 90%25. Moreover, the specialized Lorentzian fitting analyses of the 2D bands in Fig. 26, together with the matched FWHM and ID2/IG values 27, can help confirm the predominant Bernal stacking configuration of this CVD-grown bilayer graphene foam. This is also in line with subsequent X-ray diffraction (XRD) results showing an interplanar spacing d002 of ~3.35 Å ). The weak D band from the Ni-free bilayer graphene indicates the mere existence of some intrinsic structural defects originating from the edge planes, grain boundaries, vacancies, or geometrical curvatures of the graphene sheets17. These defective sites on graphene are essential in coordinating the 3D nanoporosity17 as well as suppressing the aforementioned restacking effect29. Combining the preparation mechanism and the above characterization results, we presume that such bilayer graphene foam can help elucidate the Li-storage mechanism in graphene-based electrodes.As shown in Fig. 6 in ethylene carbonate/dimethyl carbonate in R2032-type coin cells, the common half-cell configuration2 was adopted for the electrochemical characterizations of the freestanding bilayer graphene foam. For graphite-based LIBs, it is well known that (1) the insertion/deinsertion potential of Li+ ions is always below 0.3 V (vs. Li+/Li)31, a range that contributes to the overwhelming capacity of graphite (close to 372 mAh g−1), and that (2) the inevitable solid-electrolyte interphase (SEI) is usually generated at above 0.5 V during the initial charging–discharging cycles34. Both the highly reversible galvanostatic charge–discharge (GCD) measurements  that are close to the theoretical value of LiC12 at 8040 C mol−1  to gain deep insight into the Li-intercalation behavior in bilayer graphene. Clearly, there are seven intrinsic and quasi-reversible redox peaks in each CV profile . Compared to those reported for graphite36, other than the emergence of one new pair of redox peaks , especially considering the staged distribution densities of Li atoms on the X–Y plane  between the CV peak-current response (i) and the sweep rate (ν), the pseudocapacitive intercalation for Li+ ions, namely the surface-controlled behavior with b ≈ 1.0 at the initial C5–C3 and unique C1 stages, tended to become slow solid-state diffusion (like the case in a battery with b ≈ 0.5) for the PI generation , further verified this rate-determining step. These values and their trends are also similar to those of natural graphite electrodes (DLi+ ≈ 10−9–10−7 cm2 s−1)45. Obviously, it is the planar distribution density of Li atoms, not the number of graphene layers, that intrinsically determines the intercalation kinetics of Li-graphene/graphite products, in line with the above-mentioned 2D model , all the characterization results are statistical and thus can reflect the macroscopic features and general phenomena. Firstly, the highly reversible in situ Raman spectra9 for this graphene electrode , ex situ Raman spectroscopy, transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS) techniques  by the outer graphene sheets in the CRC-stacking configuration31. Furthermore, according to the simultaneous XRD patterns of the typical bilayer and multilayer electrode samples  to Li atom (radius: 1.52 Å))28, the d002 value  seemed to increase slightly in the foregoing P5−P3 phases of ARB stacking (<0.02 Å), only relying on a small population of Li atoms. However, after the unstable P2 phase48 with a theoretically transitional stacking configuration from ARB to ARA28 28. These inequalities likely result from the varied electrostatic repulsions between neighboring graphene layers bonding with the interbedded Li atoms of different volume concentrations  and the following ex situ XPS results also favor these observations and discussions. That is to say, Li intercalation into the interlayers of various graphenic carbons not only follows similar mechanisms in the 2D plane  and Li-free graphene sheets at the highly lithiated PI or P1 phases  and 0.40 (1.17) for A–B (A–A) stacking C6C6 and C6LiC6, respectively). In particular, for the P3 phase with a large enough but still unsaturated Li concentration, the plentiful vacancies would make the initial movements of its interlayered Li atoms rather disordered , when the peaks at 52–51 eV were ascribed to metallic Li species (like in the ARB mode)50. Thus, from the point of view of chemical composition change, the combined experimental and theoretical results further reveal and verify the phase-wise stacking configurations suggested by the XRD and SAED characterizations performed at different analytical ranges. This is seen in: the maintained ARB structure at P5  and P4  modes at P3 (C14LiC14) with a large enough Li concentration  with ionic Li 1s species of high BE 47 and a simultaneous nearly single C 1s species. In brief, upon the Li intercalation, the holistic ionic character of Li atoms is enhanced along with the stacking configuration transformation, while the metallic character decreases .In view of the roughly equal concentrations (at 50 ± 3 at.%) and the common source of their O components  t 28 Fig. , and (3) 28 Fig.  accordin 28 Fig. , the obs 28 Fig. , and the 28 Fig. . All theits Fig. .Fig. 5ScD graphenic carbon material. It is found that there is no fundamental difference between bilayer or fewlayer graphenes and graphite electrodes in the Li-storage manner and kinetics behavior, and the whole Li-storage process goes through four-time fractal-way Li intercalations to achieve the saturated composition of LiC6, with the final step the rate-controlling step. This study not only clarifies the Li-storage mechanism for commercial graphite anodes, but also highlights the potential of defect-free graphene in LIBs to guide its development in the energy-storage field.In summary, by developing a high-quality freestanding bilayer graphene foam and systematically studying various aspects of Li storage in it , we have demonstrated that Li atoms can only intercalate into graphene interlayer and proposed a planar Li-storage model for 230Mn70 foil in 2.0 M (NH4)2SO4 solution for 10 h, was put at the center of a quartz tube (φ30 × φ27 × 1000 mm) of the CVD furnace. The initial flow of Ar was 500 sccm until that the temperature reached the low temperature Tl shown in Supplementary Fig. Th, the flow of Ar and H2 was gradually increased to be 2500 and 100 sccm, respectively. After the above reduction pre-treatment, benzene  was introduced with the gas flow of Ar and H2 for graphene growth. For bilayer graphene, the initially total pressure and the partial pressure at the tube’s front end should be controlled at 5–6 and 0.5–0.7 Mpa, respectively. The minimum Tl value was determined to be 700 °C, below which a large amount of defects would generate on the graphene sheets. The furnace was immediately opened to let the inner quartz tube rapidly cool to room temperature with a fan  for the target material.Nanoporous Ni foam, by directly dealloying the Ni2O < 0.5 p.p.m., O2 < 0.5 p.p.m., MBraun, Unilab) with LiPF6 solution of 1 M in ethylene carbonate (EC)/dimethyl carbonate (DMC) (EC:DMC = 1:1 vol/vol) as the electrolyte, the freestanding graphene foams, the graphene@np-Ni composites, monolayer graphene on plate Cu foil, bilayer graphene on plate Ni foil directly as the working electrodes, fresh Li foil as the counter electrode, and Whatman glass fiber as the separator. No binder was adopted for the coin-cell assembly. For the graphite electrode supported by Rany Ni current collector or not, polytetrafluoroethene (with the mass ratio to graphite powder at 1:9) dissolved in ethanol was used as the binder. Both GCD and CV measurements were carried out at room temperature on an electrochemical workstation and a battery-measurement equipment. The alternating-current electrochemical impedance spectrum with varied open circuit voltages were recorded simultaneously at a frequency range from 100 kHz to 0.1 Hz and an amplitude of 5 mV. ZView software was applied to simulate the Nyquist plots in view of the reported equivalent electric circuit proposed for graphite electrode42.Coin 2032-type test cells were assembled in a high-purity argon-filled glove box (HKα radiation and nickel filter (λ = 0.15406 nm), and the operating voltage and current were 40 kV and 30 mA, respectively. A micro-Raman spectrometer (Renishaw InVia RM 1000) with laser wavelength of 514.5 nm (excitation energy: 2.41 eV) was used for Raman measurements. The laser power was set at 2.0 mW to avoid possible damage by laser irradiation. The spectrum acquisition time was 150 s. The surface species of the samples were determined by XPS  with an Al Kα (mono) anode at 150 W in a vacuum of 10–7 Pa. Both the Raman and XPS spectra were recorded from micron-sized regions.The microstructure was characterized by both of a field-emission SEM  and a field-emission TEM  equipped with two aberration correctors (CEOS GmbH) for the image- and probe-forming objective lens systems. The SAED patterns of each sample were recorded from areas of 30–100 nm in diameter. High-resolution EELS spectra of the samples were collected using a Gatan Enfina spectrometer, and energy dispersion was 0.5 eV per pixel. The XRD patterns were collected on X-ray diffractometer (SmartLab) using Cu To prepare lithiated graphene samples for the ex situ TEM and XPS measurements, in case of oxidation, each coin cell loading the target Li-graphene product Fig.  was disa51 was applied to generate projected electrostatic potential of the Li and C atoms. The applied accelerating voltage was set at 200 kV. Standard deviation of the random Gaussian distribution accounting for atom vibration was 0.085 Å, and phonon configuration number was 300. Considering the large area selected for the SAED, the periodic boundary condition was set in order to acquire intense Bragg peaks. Different rectangle supercells were constructed to meet the rectangle dimensional of simulated image size (1024 × 1024). Meanwhile, CaRine Crystallography 3.1 software was applied to simulate the diffraction patterns of various structure models to obtain the information of lattice spacings.The multislice method was adopted to simulate the diffraction spot brightness of various graphene-based structures. The scattering factors in ref. −1. In the static calculations of total energy, a 10 × 10 × 1 Monkhorst–Pack k grid was employed and the electron wavefunctions were expanded by using a plane wave basis set with a cutoff energy of 400.0 eV.First-principles calculations were performed by using the Vienna ab initio simulation package, based on the spin-polarized DFT. The electron-ion interactions were presented by the frozen core all-electron projector augmented wave pseudopotentials, and generalized gradient approximation of the electron exchange-correlation functional was adopted. The atomic layer distance was fully optimized until the Hellmann–Feynman force was <0.01 eV Å14 sheet and LiC6 sheet with normal in-plane lattice parameters  were constructed in the first step. Then, we restricted the Z-axis relaxation and merely allowed atoms to relax in the X–Y plane  to obtain the optimized structure achievable in theory. Finally, the above CaRine Crystallography 3.1 software was applied to simulate the in-plane lattice parameters of the new structure (namely the optimized unit cell) used for comparison with those experimental SAED data.On the one hand, to confirm the in-plane lattice-expansion phenomena of lithiated bilayer graphene induced by electron beam irradiation Fig.  and 18, X–Y plane, we fixed the interlayer spacing , restricted the in-plane relaxation, and merely allowed individual atoms to relax along the Z-axis direction in the binding-energy calculations  was calculated asEn−1)Ligraphene+ and n Li atoms interlaminated between two graphene atomic layers. μLi is the average Li chemical potential calculated as the unit cell merely contains isolated Li atoms. As for the BE of different equivalent C sites in different stacking configurations with Li interlaminated, its value was calculated asV). Similarly, μC is the average C chemical potential calculated as the unit cell merely contains the specific isolated C atoms.On the other hand, considering different configured Li sites relative to carbon lattice in the ons Fig. . The litSupplementary InformationPeer Review File


Graphene, a two-dimensional nanomaterial, has shown tremendous promising applications in a broad range of fields. Mass production of defect-free graphene is a prerequisite for its applications. In this work, by using a needle valve, we propose a simple hydrodynamic-assisted exfoliation method to produce high-quality few-layer graphene flakes. The prepared graphene flakes, with an average layer of 5 (~ 71% less than five layers) and a Raman D/G intensity ratio as low as 0.1, are free of defects and oxidation. The average thickness and length of the few-layer graphene flakes are 2.3 nm (~ 90% < 4 nm) and 1.9 μm (~ 50% in the range of 1–7 μm), respectively. In a lab-scale trial, the concentration of graphene can reach 0.40 g/ml under mild operating conditions , and the corresponding production rate is 0.40 g/h. The hydrodynamic-assisted exfoliation by needle valve potentially offers a simple and efficient method for large-scale production of high-quality graphene. Graphene, a single layer of graphite, has been attracting growing attention since its discovery in 2004 . Owning To date, many methods such as micromechanical cleavage , chemicaID/IG, a measure of defect content) and low aspect ratios. For example, Liang et al. [ID/IG value of 0.38 for jet cavitation exfoliated graphene, while the length was unknown. The graphene produced by kitchen blender  and high-pressure homogenizer  were also featured with high ID/IG values and low aspect ratios [ID/IG and length in the range of 0.14–0.78 and 0.02–1.41 μm [Recently, as an alternative pathway, fluid dynamics-assisted liquid phase exfoliation, has been proposed to produce graphene with low defect content on large-scale , 23–33. g et al.  reportedt ratios , 31. Dif–1.41 μm –33, respN-methyl pyrrolidone aqueous solution as solvent [In this work, a simple method based on hydrodynamic mechanism was proposed for scalable production of high-quality few-layer graphene flakes. A simple needle valve was used as exfoliation device. The exfoliation process was exemplified using 80 wt%  solvent , 35. QuaN-methyl pyrrolidone (NMP) (purity 99.5%) and graphite powder  were purchased from Aladdin Industrial Corporation in Shanghai (China). Deionized water was purified by a laboratory water purification system .A schematic view of the needle valve used for exfoliation is shown in Fig. The morphology and size of graphene were analyzed by SEM . Samples for SEM were coated with gold in an argon atmosphere. TEM was performed by a Tecnai G2 F30 S-Twin and operated at 300 kV. The samples were prepared by dropping the graphene dispersion onto holey carbon grids. AFM images were captured in tapping mode using a Bruker Dimension Icon. A newly cleaved mica was used as substrate for AFM analysis. Raman spectroscopy was conducted with a Lab RAM HR800 (λ = 532 nm) at room temperature. XPS was employed to detect the oxidation defect of graphene using an ESCALAB 250Xi analyzer. UV-Vis absorption was performed to measure graphene concentration by a Lambda 35 spectrophotometer (PerkinElmer) at a wavelength of 660 nm.Figure To identify the formation of mono-layer or few-layer graphene, TEM analysis was performed to visually observe the number of graphene layers. Figure To further identify the thickness and length of graphene, AFM analysis was performed by using mica wafer as the substrate. Shown in Fig. −1), G band (~ 1580 cm−1), and 2D band (~ 2700 cm−1) were observed for these two graphitic materials. For graphene, the 2D band was in the shape of symmetric peak. The full width at half maximum (FWHM) of G band was 13 cm−1, well matching with the previous reports for thin graphene flakes (12–14 cm−1) [ID/IG) for the prepared graphene was 0.10, lower than that of ultrasonication exfoliated graphene (0.29) [Raman spectroscopy was performed to detect the defect content of graphene. Figure 14 cm−1) . Moreovee (0.29) , shear fe (0.29) , 26, ande (0.29) , 32, furThe oxides content of the prepared graphene flakes was investigated by XPS. As shown in Fig. P), number of cycles (N), and initial concentration of bulk graphite (Ci), on the concentration of few-layer graphene dispersion were investigated.To maximize the productivity of few-layer graphene, the effects of operating parameters, that is, working pressure , the concentration obviously increased with increasing working pressure from 1 to 20 MPa, and a concentration as high as 0.40 mg/ml was reached at 20 MPa. However, further increasing the working pressure to 30 MPa, no significant increase in the concentration was observed. Such results may be explained by the following reasons. In hydrodynamic-assisted exfoliation process, increasing in the working pressure results in an increase in the collapse intensity of cavity, due to which there is an increase in the magnitude of the stress derived from cavitation and turbulent, thereby favoring the delamination of graphite. The concentration did not change appreciably above 20 MPa, probably due to the agglomeration and re-stacking of graphene flakes caused by the rise of temperature under higher working pressure [As shown in Fig. pressure .Fig. 8EfP = 20 MPa, Ci = 10 mg/ml). As expected, the concentration was increased with increasing number of cycles. With 16 cycles, the concentration reached a maximum value of 0.4 mg/ml. However, further increasing the number of cycles, the concentration was basically unchanged. In the exploitation process by needle valve, passing the suspension through the valve more than once could result in the fragmentation of graphite, which was favorable for exploitation due to the fact that smaller graphite pieces are easier to delaminate into graphene than larger ones [Figure ger ones . Howeverger ones . TherefoP = 20 MPa, N = 16), the concentration increased from 0.146 to 0.40 mg/ml with increasing the initial concentration of graphite from 2 to 10 mg/ml. In liquid phase exfoliation process, particle-particle collisions are beneficial to the delamination of graphite. A higher initial concentration of graphite leads to the reinforcement of particle collision, thereby contributes to the self-exfoliation of graphene [Initial concentration of bulk graphite also had a significant influence on graphene concentration . As showgraphene . When thgraphene  and Araographene , indicatID/IG of the few-layer graphene produced by different fluid dynamics methods. The graphene produced by needle valve had a concentration as high as 0.40 mg/ml, which was higher than most of the reported values. In a lab-scale trial, the production rate was calculated to be 0.40 g/h. The concentrations reported by Varrla et al. [ID/IG as low as 0.1 (lower than the reported ratios). Therefore, it can be concluded that the hydrodynamic-assisted exfoliation by needle valve was an efficient approach to produce few-layer graphene flakes with high quality.Table a et al.  and Araoa et al.  could reWe suggest the superiority of the hydrodynamic-assisted exfoliation be ascribed to the exfoliation mechanism. Considering the structure of the needle valve, the flowing fluid dynamics effects are responsible for the delamination of graphite: First, when the suspension containing graphite passes through the narrow gap of the valve, the total pressure of the liquid falls sharply below its vapor pressure. As a result, a turbulent jet that causes huge hydrodynamic stress is formed at the outlet of the valve and generating a large volume of cavitation bubbles. The bubbles then grow from micro gas nucleuses and subsequently collapse intensely. With the collapse of bubbles, intensive microjets and shock waves that surround the graphite are generated, thus resulting in the delamination . Second,ID/IG ratio as low as 0.1 were free of defects and oxidation. In a lab-scale trial, the concentration of few-layer graphene could reach 0.40 mg/ml under mild operating conditions , and the corresponding production rate was 0.40 g/h. Hydrodynamic-assisted exfoliation by needle valve was potentially an efficient method for scalable production of high-quality graphene.In summary, we have demonstrated the production of high-quality few-layer graphene using a simple hydrodynamic-assisted exfoliation method. The results indicated that ~ 71% of the prepared graphene flakes were less than five layers, while the average thickness and length of the flakes were 2.3 nm (~ 90% < 4 nm) and 1.9 μm (~ 50% in the range of 1–7 μm), respectively. The flakes with


The geroscience hypothesis holds that targeting fundamental mechanisms of aging has the potential to prevent or reduce severity of multiple age-related diseases. Cellular senescence is a key mechanism that may be driving disease in human aging, including Idiopathic pulmonary fibrosis (IPF), a progressive, ultimately fatal, senescence-associated disease. Importantly, cellular senescence may be targeted therapeutically. Senolytic agents are drugs that selectively induce senescent cell apoptosis by transiently disabling anti-apoptotic pathways. Selective ablation of senescent cells using the senolytic drug combination dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered IPF mouse model. We conducted the first-in-human trial of senolytics in IPF patients, and our data indicate that short-term, intermittent administration of DQ may alleviate physical dysfunction that accompanies IPF in human aging, including clinically-meaningfully improvements in mobility (p<0.05). This geroscience-guided clinical feasibility study supports evaluation of senolytics in larger randomized, controlled trials of cellular senescence-associated age-related diseases.


Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. The treatment is challenging and nowadays a comprehensive approach based not only in pharmacological strategies is necessary. Identification and control of comorbidities, non-pharmacological treatment, prevention and management of exacerbations as well as other areas of care  are fundamental for a holistic management of IPF. Gastroesophageal reflux, pulmonary hypertension, obstructive sleep apnea, combined with emphysema, lung cancer and cardiovascular involvement are the main comorbidities associated with IPF. Non-pharmacological treatment includes the use of oxygen in patients with rest or nocturnal hypoxemia and other support therapies such as non-invasive ventilation or even a high-flow nasal cannula to improve dyspnea. In some patients, lung transplant should be considered as this enhances survival. Pulmonary rehabilitation can add benefits in outcomes such control of dyspnea, exercise capacity distance and, overall, improve the quality of life; therefore it should be considered in patients with IPF. Also, multidisciplinary palliative care programs could help with symptom control and psychological support, with the aim of maintaining quality of life during the whole process of the disease. This review intends to provide clear information to help those involved in IPF follow up to improve patients’ daily care. Idiopathic pulmonary fibrosis (IPF) is a progressive and unpredictable disease with a poor 5-year survival outcome and great impact on patient’s quality of life. Therefore, improving survival has been the main objective of research studies and the goal of IPF’s treatment. In the last decade, scientific evidence changed the perspective of the disease by demonstrating the efficacy of two drugs in slowing down the loss of lung capacity in patients with IPF.Despite of these promising new treatments, IPF remains an incurable disease with a complex comprehensive approach. In this respect, optimal management may include comorbidity identification and treatment, as well as non-pharmacological interventions such as ambulatory oxygen, pulmonary rehabilitation and lung transplant.Besides, during the past century life expectancy has improved significantly, especially in developed countries. In these societies, quality of life (QOL) has become an important issue, particularly in older ages with significant comorbidities. This population is well represented by IPF patients. So, QOL is also a goal of the management plan. Nonetheless, palliative care plays a very important role as one of the main keys in preserving QOL and alleviating symptoms.In the current article, we will review the most recent medical literature about IPF comorbidities, complications and non-pharmacological treatment in order to provide clear information to help those involved in IPF follow up to improve patients’ daily care.Management of comorbidities in IPF is very important due to their significant impact in life expectancy and quality of life. However, due to the few well-designed clinical trials in this field quality data is scarce, and most recommendations are based in expert opinions or single centers experiences. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure ≥25 mmHg evidenced on right heart catheterization—the gold standard procedure for diagnosis —althoughPH should be suspected in patients with evidence of right heart failure on physical exam, dyspnea or oxygen desaturation out of proportion for their pulmonary function, disproportionately low diffusion capacity, or evidence of pulmonary artery enlargement or right ventricular hypertrophy on imaging studies. Transthoracic echocardiogram is the study used to screen for PH and right ventricular systolic pressure >35 mmHg has a sensitivity of >85% for detecting PH in patients with IPF [Besides, PH could be aggravated by other comorbidities, such as obstructive sleep apnea (OSA), pulmonary thromboembolic disease, emphysema or cardiological abnormalities (ventricular diastolic dysfunction). Therefore, it is important to screen for these conditions and treat them if necessary.No effective therapy has been established for PH associated with IPF. In ATS/ERS/JRS/ALAT 2015 guidelines  authors Despite this results, nitric oxide pathway treatment showed a possible benefit as some secondary outcomes were positive . Trials Combined pulmonary fibrosis and emphysema (CPFE) prevalence is around 30% in IPF patients. There is still controversy about the amount of emphysema observed in high-resolution computed tomography to define CPFE, and it is proposed ≥10% emphysematous involvement throughout the lungs. Because of the distinct clinical, functional, radiological, and pathological characteristics of CPFE, it has been proposed as a phenotype of IPF or as a separate clinical entity [Individuals with CPFE are usually male with an extensive smoking history and increased oxygen requirement. The pulmonary function test often shows relatively preserved total lung capacity and forced vital capacity (FVC), with a disproportionate reduction in the diffusion capacity of the lung for carbon monoxide (DLCO). The incidence of pulmonary hypertension (50%) and lung cancer (47%) is higher in this group, with an increased risk of death in some cohorts .General treatment recommendations in these patients includes smoking cessation, inhaled bronchodilators according to chronic obstructive pulmonary disease guidelines, oxygen therapy (if there is an indication), rehabilitation, vaccines and lung-transplant evaluation. Both Pirfenidone (ASCEND) and Nintedanib (INPULSIS 1–2) trials included patients with emphysema. Despite the inclusion of emphysema patients, all the variability of patients with CPFE was not represented in those trials because patients with airway obstruction and lower DLCO were excluded. With the aforementioned trials, the efficiency of these antifibrotic drugs was maintained in the subgroup of patients with emphysema .The prevalence of OSA in IPF patients has been reported from 10–88% and is often undiagnosed. In the Lancaster et al.  study, mThe presence of OSA was associated with a more rapid clinical deterioration independent of the severity of IPF. OSA with prolonged sleep-related desaturation was associated with worse prognosis, both in terms of mortality and clinical deterioration .There are several theories to explain the relation between OSA and IPF. It has been suggested than the main contributor is the impairment of the upper airway stability due to decreased lung volumes, especially during the REM (rapid eye movement) phase. This can facilitate the upper airway collapse. On the other hand, intermittent hypoxia, produced in OSA, is a potent stimulus to oxidative stress causing systemic inflammation and tissue damage that could carry out progression of pulmonary fibrosis .The initiation of continuous positive airway pressure (CPAP) has shown to improve daily activities and quality of life measures . Also, iGastroesophageal reflux (GER) is highly prevalent in patients with IPF (87–94%), with almost half of the patients being asymptomatic. GER and microaspiration have been proposed as risk factors for the development and progression of IPF . Both acRecently, alkaline reflux has also been linked to alveolar injury in epithelial cells, playing a part in pathogenesis of IPF and also increasing the risk of exacerbations. Hypothesizing a potential benefit in controlling acid and non-acid GER, Raghu et al.  evaluateStenotrophomonas spp. and Campylobacter spp. The presence of Campylobacter spp., a gastrointestinal pathogen, in the respiratory microbiota is supposed to have arisen from silent microaspiration of gastric contents.Finally, microaspiration has been proposed to have a role in the development of AE-IPF. The association between microaspiration and AE-IPF was strengthened in a recent study by Molyneaux et al. . In thisThe importance of this comorbidity was highlighted in the study of Nathan et al. , as cardCoronary artery disease has an estimated prevalence of 3–68% in IPF patients, sharing several risk factors as male gender, increasing age and smoking history . Other cCoronary disease could be increased by the promotion of atherosclerotic effects hypothesized of pulmonary fibrosis, mediated by increasing serum levels of interleukins, cytokines and circulating immune complexes. Interleukin-4 (IL-4), Interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) are involved in angiogenesis and are also present in fibro-proliferative processes beyond the lungs. All these disorders might explain the possible mechanisms of increased atherogenesis .Dyspnea not fully explained by the severity of IPF should be evaluated with an electrocardiogram, stress radionuclide myocardial perfusion imaging, or stress echocardiography should be considered .Treatment of cardiovascular comorbidities in this group of patients do not differ from the general population.The incidence of lung cancer in IPF patients ranges from 1–48%. IPF is an independent risk factor for lung cancer in addition to smoking .Therapeutic modalities need to be determined in this group, because interventions could provoke exacerbations of IPF. A study in patients with non-small cell lung cancer (NSCLC) who underwent surgery showed that the survival to five years was 40%, referring to reduced early dead with wedge resection (caused by respiratory failure) and long-term better prognosis with lobectomy .Acute exacerbation increased also with chemotherapy  and with radiotherapy . InterstPirfenidone was proposed to reduce acute exacerbations after surgery in the PEOPLE Study (“Efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection”). . FurtherReduced mobility with venous stasis and a probable involvement and activation of the coagulation cascade is involved in the pathogenesis of IPF, evidenced by elevated levels of tissue factor and fibrin; this increases the risk of venous thrombosis and, consequently, pulmonary embolism (PE) .Epidemiological analysis reported a relationship between thromboembolic phenomenon and pulmonary fibrosis ,33. In fConsidering this, Leuschner et al.  conducteRegarding thromboembolic phenomenon management, prolonged treatment with anticoagulants is necessary. Both American and European guidelines ,38 recomThe 2011 guidelines for diagnosis and management of IPF  made a sIn order to investigate the relationship between IPF and DM, a Chinese group performed a systematic review on this topic . After rThe prevalence of hypothyroidism is 1–2% for men and 5–9% for women being the autoimmune thyroiditis the most common etiology . In a caAnxiety and depression are comorbidities commonly find in patients with interstitial lung diseases including IPF. The prevalence of anxiety ranges from 30–50% while the prevalence of depression from 20–30% ,45. AnxiRecently, Glaspole et al.  performeIn the same line, a recent Cochrane review  highlighIn conclusion, there is still some doubt about the directionality of this relationship between IPF and symptoms of anxiety and depression. However, what is clear is that the need for pharmacological or behavioral therapy must be detected early and assessed individually in order to improve global management of IPF and quality of life.The main complication of IPF is the acute exacerbation, a condition that remains unpredictable and it is associated with a high risk of death. The continuous search for risk factors and clinical predictors for exacerbations is needed in order to improve the management of those patients.In 2016 the international working group for AE-IPF reviewed the definition of acute exacerbation. The new definition describes any acute (less than a month), clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by the presence of new bilateral ground-glass opacity and/or consolidation not fully explained by cardiac failure or fluid overload .The most important risk factors for AE-IPF are low forced vital capacity, rapid decline in FVC (less than six months), high alveolar-to-arterial oxygen pressure difference, pulmonary hypertension at the time of evaluation for lung transplantation, gastroesophageal reflux and air pollution .There is no proven effective treatment for AE-IPF. The 2011 IPF guidelines recommended supportive care and suggested that most patients could be treated with corticosteroids, without clear evidence to support this approach . While rLung transplantation is proposed for appropriate patients with IPF, according to IPF guidelines. Transplant eligible patients should be referred to a transplantation center for early evaluation in the course of their disease, preferably before an episode of AE-IPF. Mechanical ventilation and extracorporeal membrane oxygenation are proposed as bridge for transplantation candidates. A more strict selection criteria for patients candidates to mechanical ventilation and the use of protective ventilation strategy could improve AE-IPF prognosis .p = 0.0047) [Moreover, treatment with nintedanib is proposed to reduce the risk of developing an acute exacerbation although no statistically significant difference in the incidence rates of investigator reported acute exacerbations in the nintedanib and placebo groups were seen . The com 0.0047) .Pirfenidone could reduce the incidence of postoperative AE-IPF in patients with lung cancer and it´s safe to be use in these circumstances . BesidesOther proposed treatment is the recombinant human soluble thrombomodulin, which has an anti-inflammatory, anticoagulant and antifibrinolytic effect, that had favorable mortality rate in some uncontrolled studies and is now been test in a phase three clinical study .Other promising treatments that are in study are hemoperfusion with polymyxin B-immobilized fiber column and therapies against autoantibodies .Statins and anti-acid treatment were proposed to reduce incidence of AE-IPF, with prospective studies needed to confirm this hypothesis ,54.Current IPF treatment guidelines highlight the importance of non-pharmacological treatment in these patients. In the IPF is associated with increased dyspnea and therefore, with a hypermetabolic state and high resting oxygen consumption. It is not unusual to observe a reduction in body weight and loss of muscle mass that contributes to reduction in functional capacity and low physical activity. Therefore, nutritional counseling is very important in the global management of IPF patients. This is even more important in patients referred to for lung transplant.In smokers it is very important to provide information about smoking cessation assistance. As other chronic lung diseases, smoking increase the risk of presenting with other severe comorbidities as lung cancer and co-existence of emphysema. So, quitting smoking is a cornerstone of management.Regarding vaccination, no specific studies have been conducted in IPF patients. Although, as with other patients with chronic respiratory diseases, they have a higher risk of suffering from respiratory infections. Hence, the annual influenza and anti-pneumococcal vaccination is recommended in all patients.Compared to other chronic respiratory diseases, exertional hypoxemia is a common finding in IPF. However, hypoxemia at rest usually occurs in the final stages of the disease, which means the subsequent indication for ambulatory oxygen. The prescription of oxygen may reduce breathlessness and increase physical capacity by improving the gas exchange. But also, ambulatory oxygen is helpful in the treatment of frequent comorbidities in IPF associated with poor prognosis such as pulmonary hypertension and right heart failure.There is scarce evidence with no clinical randomized trials to evaluate the benefit of oxygen in interstitial lung disease, including IPF. Results of the low-quality evidence provided by retrospective studies are contradictory. For example, Douglas et al.  analyzed2;  of 96% standing. A directly proportional relation between the oxygen flow and the mortality was shown, independent of other factors as FVC and 6-MWT results. Other studies demonstrated that ambulatory oxygen improves exercise capacity in IPF patients [Regarding exertional dyspnea, it is well known that exercise limitation and increase of dyspnea have an important impact on quality of life. In fact, hypoxia during the 6 min walking test (6-MWT) is an independent prognostic factor of mortality and disease progression ,60,61. Lpatients . In the patients .2  <55 mmHg or resting PaO2 <60 mmHg with evidence of polycythemia (hematocrit greater than 55%), pulmonary hypertension or cor pulmonale. This well-accepted relationship between the use of long term ambulatory oxygen and improved health outcomes in COPD raises the possibility that it could have similar effects in ILD. Therefore, although there is no strong demonstrated evidence of survival benefit, the use of oxygen in patients with rest or nocturnal hypoxemia (SpO2 < 88%) is recommended by International Guidelines [Taking into account the previous mentioned, and considering the lack of studies supporting a survival benefit from ambulatory oxygen in IPF patients, the indications and use of oxygen therapy in IPF is extrapolated from the experience in COPD. The use of long term oxygen in those patients is well established, based mostly on two principal clinical trials performed in that group: the nocturnal oxygen therapy trial (NOTT)  and the idelines . Also, iAn acute life-threatening hypoxemia during the course of IPF occurs in a 5–10% of patients. This event may lead to consideration of invasive or non-invasive ventilatory support (NIV) as other new options as extracorporeal membrane oxygenation (ECMO) or high-flow nasal cannula (HFNC) oxygen.2 (Fraction of inspired oxygen) delivery. The therapeutic benefit includes reducing the rate and work of breathing and improving oxygenation. Also, the humidification improves secretion clearance and maintenance of mucosal integrity in a more comfortable way for the patient. One of the advantages versus NIV is that it requires less training and can be applied outside ICUs. Although it is a promising treatment, the specific role in ILD is yet unknown given the lack of specific studies, except case series reported. More studies are needed to evaluate the real benefit to guide an adequate indication of this therapy. Nowadays in clinical practice, it has been used depending on the availability and center experience. Mostly to avoid more invasive procedures in exacerbations while adjusting specific etiology treatment or waiting for lung transplant.In IPF hospitalizations, especially in acute exacerbations, oxygen therapy even in high concentrations is the main support therapy, given the significant hypoxia produced by an important mismatch of ventilation/perfusion ratio (V/Q) with severe diffusion impairment . Due to Regarding mechanical ventilation, is known that patients admitted to the intensive care unit with acute respiratory failure needing invasive ventilation have a very poor prognosis  with a hIn this context, NIV may be an appropriate option with an important role in improving dyspnea. Vianello et al.  performeAnother possible strategy is the use of ECMO or veno-venous ECMO in patients awaiting a lung transplant that suffer an acute worsening . The firIPF is a progressive disease with poor prognosis. In the past years, new pharmacological treatment has been developed with good results in slowing down the progression of the disease. Despite the pharmacological advance, it remains an incurable disease where lung transplant plays an important role and should be considered in some patients as it enhances survival. Determining the time to referral and register on the transplant list could be difficult. In order to advice physicians, in 2015 the International Society for Heart and Lung transplantation released guidelines on the selection of lung transplant candidates . The guiHistopathologic or radiographic evidence of usual interstitial pneumonitis or fibrosing non-specific interstitial pneumonitis, regardless of lung function.Abnormal lung function with FVC <80% predicted or DLCO <40% predicted.Any dyspnea or functional limitation attributable to lung disease.Any oxygen requirement, even if only during exertion.For inflammatory interstitial lung disease (ILD); failure to improve dyspnea, oxygen requirement, and/or lung function after a clinically indicated trial of medical therapy.The timing of referral is wider and includes:Decline in FVC >10% during six months of follow-up.Decline in DLCO >15% during six months of follow-up.Desaturation to <88% or distance <250 m on 6 MWT or 450 m decline in 6 MWT distance over a 6-month period.Presence of pulmonary hypertension on right heart catheterization or 2-dimensional echocardiography.Hospitalization because of respiratory decline, pneumothorax, or acute exacerbation.Regarding when is recommended to list these patients for transplant; the following situations were proposed:In addition to the above, it is also important to ensure adequate nutritional status and social support.Another initiative to improve the selection of candidates for lung transplant was published in May 2005 by the United Network for Organ Sharing: the Lung Allocation Score (LAS). The LAS is nowadays a widely used method in many countries to identify the best candidates for transplant. The score is calculated using different measures of patient’s health that estimate survival probability and projected duration of survival with or without lung transplant. Since the implementation of LAS, a greater number of IPF patients received a lung transplant and the percentage of patients on the waiting list with restrictive lung disease has increased . In factConsidering the type of procedure, both single and bilateral lung transplantations are performed in IPF patients and there is still a current debate on the election method. The lack of randomized trials to compare the both procedures does not allow showing a significant difference between single or bilateral transplantation, although some retrospective studies point out that survival could improve in patients with a bilateral lung transplant ,77.In one study, patients with IPF who received a lung transplant showed a 75% reduction in risk of death compared with patients who remained on the waiting list. Risk of mortality while waiting for lung transplantation is significantly greater for patients with IPF compared with cystic fibrosis and emphysema . The oveAccording to the above mentioned and international guidelines, patients with IPF should be considered for lung transplant at the time of diagnosis to achieve an early referral to evaluation.Pulmonary rehabilitation (PR) is defined by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors” .In ILD, it is well known that exercise intolerance is an important feature due to its association with exertional dyspnea. Low physical activity is related to a deterioration in quality of life and poor survival . In the The duration of PR programs varies between 6–12 weeks but is not well established because of the yet few patients included in the studies performed with ILD and IPF patients. Likewise, rehabilitation programs are not standardized and vary based on local practice. However, those programs usually perform muscular training with strength and resistance exercises and also respiratory reeducation through control of respiration techniques and diaphragmatic effort to prevent tachypnea, anxiety and to improve gas exchange.Until recently, most respiratory rehabilitation studies had been conducted in COPD. Nowadays, new evidence suggests a short-term benefit of those programs in ILD patients. For example, a Cochrane review in 2014 showed that pulmonary rehabilitation reduced dyspnea, increased walked distance (average difference of 44.34 m in ILD and 35.63 m in IPF) and improved quality of life . BesidesDespite the aforementioned, pulmonary rehabilitation is weakly recommended in the international guidelines of the ATS/ERS/JRS/ALAT, as the long-term benefit of pulmonary rehabilitation remains unclear. Further large randomized control trials are needed to explore the best IPF-specific PR protocol, optimum duration and aftercare to assess long-term benefits.The management of idiopathic pulmonary fibrosis (IPF) should be oriented to a multidisciplinary care approach, including control of symptoms and psychological care, as this disease affects the quality of life of the patient, as well as that of his family and caregivers.The World Health Organization defines palliative care as the “approach that improves the quality of life of patients and families who face the problems associated with life threatening diseases, through the prevention and alleviation of suffering through the early identification and impeccable evaluation and treatment of pain and other physical, psychological and spiritual problems.” It is evident that this is the situation of many patients affected by IPF, given the evolution and progression of this disease.Gómez-Batiste , identifDepression and anxiety, related to the diagnosis and prognosis, is prevalent in patients with IPF. It has a significant impact on QOL. So, it is important to perform a psychological assessment regularly in these patients.Few studies have evaluated the role of palliative care in IPF, and these show shortcomings in the control of symptoms, psychological care and the planning of last wills. It also reveals the need to develop a strategy for the evaluation, treatment and monitoring of the palliative needs of patients . This wiThere are studies suggesting that the implementation of a multidisciplinary care model, including palliative care, in IPF patients, is associated with a decrease in the number of admissions in the situation of last days, as well as in the consumption of health care resources in the last year of life . PatientIn conclusion, the early inclusion of patients with IPF in an advanced phase in a multidisciplinary palliative care program helps to adequately control symptoms, psychological support and makes decisions regarding the end of life, with the aim of maintaining the quality of life during the whole process of the disease.Management of IPF is a challenge for respiratory physicians due to the unpredictable course of the disease and the significant impact in QOL and survival. Beyond pharmacological treatment, a comprehensive approach includes non-pharmacological therapies. An example is the growing role and value of palliative care in patients with advance disease or poor symptoms control.Regarding comorbidities, in this review we have provided evidence-based information to highlight the value of an early assessment and management.Acute exacerbation remains the main complication of patients with IPF. In recent years, there has been a significant interest in this field but still there is no effective treatment and prevention remains the clue.