The top priority of fire management agencies in Canada is to protect human life and property. Here we investigate if decades of aggressive fire suppression in the boreal biome of Canada has reduced the proportion of recently burned forests  near human communities, and thereby inadvertently increased the risk of wildfire. We measured the percentage of RBF, which are usually less flammable than older forests, up to a 25-km radius around communities compared to that in the surrounding regional fire regime zone. Our analysis of 160 communities across boreal Canada shows that 54.4% exhibited a deficit or lack of RBF, whereas only 15.0% showed a surplus. Overall, a majority (74.4%) of communities are surrounded by a low (≤10%) proportion of RBF, indicating a higher vulnerability of those communities to wildfire. These findings suggest that suppression policies are increasing flammability in the wildland–urban interface of boreal Canada. A primary element of modern wildfire management is to aggressively suppress small fires before they become large, but benefits can be offset by the fact that these practices promote older forests that are more ‘flammable’. Here the authors show that this downside puts numerous human communities at elevated risk of fires in boreal Canada. Identifying the drivers of this change is, however, challenging given that wildfire is a complex phenomenon influenced by several natural and human variables4. This includes changes in weather and climate resulting from increased atmospheric CO2, fuel  composition and continuity, human land use, and fire management policies and practices. Increasing population growth in wildfire-prone areas5 combined with projections of greater burn rates due to climate change could further exacerbate the risk of wildfire to people and property7. In Canada, this growing threat of wildfire requires a comprehensive approach to fire management8, of which one aspect is efficient fire suppression around communities. However, the effect that management policies and practices have had on boreal burn rates is still not fully understood9. For example, although people are responsible for more than half of ignitions in boreal Canada10, people also limit wildfire through fire-suppression activities, such as early detection and rapid initial attack, resulting in a net decrease in area burned by wildfires12. Fire suppression may thus result in a wildfire deficit that has directly contributed to an increase in the amount and continuity of flammable biomass, especially around communities14.Over the past half century, Canada’s forests have experienced an upward trend in annual area burned, particularly in western Canada1. Those large fires greatly reduce the amount of flammable material and are mostly lethal to trees15. Post-fire boreal forest stands that are <30 years in age are less likely to burn than older forests due to the combined effects of depletion of biomass after fire and the slow regrowth of vegetation  of high-latitude forests16. This leads to a reduced potential for fire ignition and subsequent propagation17, and this negative feedback between fire and fuels has been observed throughout the biome  would be substantially higher22.The wildfire regimes of the North American boreal forest are characterized by a combination of numerous small fires and relatively infrequent large high-intensity crown fires that have a disproportionate impact 24. The ‘intensive’ zone is managed with aggressive and systematic fire-suppression policies due to its greater wildland–urban interface (WUI) and natural resource-related values . In this zone, fire management is focused on aggressive fire suppression that involves rapid detection and response to extinguish low-to-moderate intensity fires, while they are relatively small . In the more remote ‘extensive zone’, fires are often monitored but generally allowed to burn with minimal intervention, unless there are human values at risk, in which case active fire suppression is employed25. Fire management agencies throughout the country prioritize public safety and community protection over other values, regardless of the fire management zone26. In other words, while fire-suppression policies may affect fire regimes over broad areas27, their impacts are most pronounced close to communities.In Canada, fire management efforts are spatially variable and can be broadly split into ‘intensive’ and ‘extensive’ fire protection zones28. Have the long-term effects of fire management policies limited the prevalence of young stands and increased forest flammability around boreal communities? If such an increase is borne out, fires burning in the vicinity of some communities will likely be more intense  and be more difficult to control than those in the overall forest matrix29. Anecdotally, recent catastrophic wildfire events in the WUI have burned through forests that had been spared by wildfires for several decades. This was the case of the 2016 Fort McMurray wildfire , which became the costliest natural disaster in modern Canadian history ($3.64 billion CND in insured losses), as this 590,000-fire spread almost entirely through forests that had not burned since the 1940s or earlier.Decades of aggressive fire suppression around communities in boreal Canada likely has altered the forest mosaic by promoting the retention of older forest stands compared to what would have occurred under a naturally functioning fire regime30. This allowed us to: (1) compare the proportion of RBF around communities to that of the corresponding FRZ, (2) identify where high fire hazard (RBF ≤  10%) communities were located, and (3) qualitatively evaluate whether communities recently impacted by wildfire were predominantly surrounded by old forest, suggesting a fire deficit and increased risk of wildfire.Here, we investigate the potential flammability of forest cover surrounding communities relative to the overall forested landscape in the boreal biome of Canada. Specifically, we calculated the proportion of forest stands that burned <30 years ago (termed ‘recently burned forests’ (RBF)) in 5-km radius concentric bands (up to 25-km) around selected communities and compared this to the RBF percentage within the forest matrix further away from communities that are considered to have similar fire regimes (hereafter ‘fire regime zones’ (FRZ); Fig. Our results show a low percentage of RBF (forests <30 years old) around most communities Fig.  and a fiA majority (74.4%) of communities in the boreal biome of Canada are surrounded by older forests  within a 10-km radius Fig. . When rep < 0.05; Mann–Whitney test) greater percentage of open water in their vicinity (10-km radius) compared to randomly selected points in that zone  varied among FRZ. Communities in most FRZ  had a significantly  spent annually on firefighting crews, equipment, and aircrafts35. While suppression has proven effective in many parts of the boreal forest12, its effectiveness is likely to degrade as limited fire-suppression resources become increasingly overwhelmed under projected climate changes36.Wildland fires are dependent on three factors that are increasingly coinciding in time and space: flammable fuels, ignitions, and fire-conducive weather26 and that most fire ignitions (per unit area) occur closest to human development, firefighting resources are often stationed in or near communities. This allows them to attack many fires when they are small and low in intensity, thus increasing the probability of successful containment37. Extinguishing wildfires before they become large increases the age of the forest and the amount and continuity of flammable vegetation near communities, thereby unintentionally amplifying the fire hazard in the long run around these same values that we seek to protect. In fact, successful fire suppression without subsequent modification of the forest  will inevitably lead to vegetation conditions characteristic of a fire deficit. This effect, termed “fire paradox”38, has already been observed in many fire-prone ecosystems of the USA (refs. 40). Our results show that this is also occurring in parts of Canada.Given that protecting people and property is the highest priority for fire management agencies41. We show that, relative to the forest matrix, there is a significant lack of RBF within 5 km and up to 25 km for many communities in the Canadian boreal biome, a majority of which are located in the western half of Canada and in FRZ where settlements are generally more remote and the burn rates are higher. However, little or no fire deficit around a community does not necessarily imply low exposure to wildfire. In eastern Canada, for example, wildfires are inherently less frequent, generally resulting in lower fire deficits surrounding communities compared to western Canada. Consequently, forests in general and those around communities in eastern Canada are considerably older than those in western Canada  that burned several kilometers into an 8-year-old forest during 2 days of extreme weather22. Identifying the specific weather conditions at which the flammable biomass limitation is overcome represents an active area of research46; however, high-resolution historical reconstructions16 and meteorological analysis of particularly extreme fire seasons, such as the 2014 season in the Northwest Territories  management50, and, where feasible, prescribed burning52. There are, however, many physical, policy, and operational challenges to overcome. Mechanical fuel treatments require continued maintenance over time, are too expensive to apply across large boreal landscapes53, and are usually not designed to halt extreme wildfires54. Unlike the forests of other North American biomes, vegetation management in the boreal forest can be less focused on modifying forest structure  and instead emphasize changes to forest composition. For example, where possible and ecologically desirable, encouraging the establishment of deciduous stands through forestry practices represents an attractive option for drastically reducing the likelihood of wildfire over larger expanses of forest55.Our results reaffirm the urgent need for a more holistic approach to wildland fire management that emphasizes proactive mitigation to complement an efficient fire-suppression system as a means to reducing the risk of wildfires to communities57, the propensity of coniferous boreal forests to burn as high-intensity crown fires can make prescribed burning a risky proposition for some residents and decision-makers. The risk tolerance to prescribed burning may, however, increase as the need for hazard reduction becomes critical. For example, in Banff, Alberta , which welcomes millions of tourists annually, Parks Canada has garnered public approval to maintain an active prescribed burning program for forests adjacent to the town since the early 1990s. The risk to the community is minimized by burning almost exclusively during the spring and fall, and by burning small parcels frequently  rather than conducting single large burns, practices that are consistent with traditional indigenous burning practices in that area51.Although prescribed burning programs in boreal forests would reset the stand age and effectively reduce wildfire potential for decades to come58. Recognizing, however, that there is no single solution or silver bullet to reducing the risk of wildfires to communities, breaking the continuity of older, highly flammable forests must be an element of a comprehensive approach to managing wildland fire risk26.Large, high-intensity wildfires are inevitable in the boreal forest and the absence of other plausible factors explaining reductions of RBF around many communities lends credence to the presumption that fire management policies, particularly fire suppression, are contributing to a fire deficit. Identifying the critical proportion of RBF necessary to substantially reduce the risk remains an open question, but even a modest increase in the proportion of RBF could be highly beneficial in some instances, especially when fire management strategies maximize the use of non- or less-flammable features across the landscape. The disproportionately high density of ignitions around communities combined with a greater continuity of older forests in some locales in boreal Canada may increase the call for more fire suppression, especially if projections of more extreme fire weather are borne out59. This region is generally bounded to the north by the transition to tundra and to the south by prairie and temperate forest ecosystems. This study area was subdivided for analysis into 12 FRZ, ecographic units considered to have similar fire regimes30. Although the zonation exists for all of Canada, only those FRZ in the boreal biome were considered, and of these, zones with fewer than six communities  were excluded from the analyses summarized by FRZ (see below). All analyses were performed using the R software v3.6.1 and ArcGIS Enterprise v10.7 for Windows.The study area included all of boreal Canada Fig. , as defi60 based on the following criteria. Communities with a population <200 (ref. 61) were excluded from the analysis because many of them were temporary (or even abandoned) settlements. We removed communities with >30% natural or anthropogenic nonfuel within a 25-km buffer  to eliminate boreal communities with largely non-forested surroundings. Communities on islands in large lakes were also excluded. Next, we retained only one community from pairs or groups within 25 km of one another to eliminate spatial overlap in the analysis. A community was retained if its population was at least twice that of these nearby communities. If this condition was not met, the community with the greatest forest cover within 10 km was retained, based on land cover analysis of 2014 forest vegetation62. Finally, the remaining 160 community centroids were spatially corrected using aerial imagery .From an initial dataset of 381 boreal communities, 160 communities were selected from a geographic dataset of populated places63. Fire polygons were rasterized at a resolution of 250 m and overlaid to calculate time since fire. All permanent nonfuel  was masked out using the kNN Canadian land cover dataset62. We produced a map of RBF by classifying any pixel with an age <30 years (1988–2017) as RBF, and any pixel with an age ≥30 years as non-RBF. Forest harvest areas, which were based on a Canada-wide Landsat-based 30-m resolution change-detection dataset from 1985–2015 , were not considered in the calculation of RBF.The National Burned Area Composite was used to analyze wildfire patterns across the study area34, for comparison; although the results were broadly similar, HFZ were too large and encompassed an unacceptable degree of variation in fire regimes, and were thus subsequently dropped.Statistics on RBF were computed for each community and FRZ. Concentric buffers, 5 km in width and centered on community boundaries, were used as analysis units, up to a maximum of 25 km. We calculated the percent RBF of the total area of forested lands within buffers after masking permanent nonfuels . To limit any interaction among neighboring communities, parts of buffers were removed where they overlapped another community’s buffer with a narrower radius . We removed all pixels within 2 km of community boundaries to limit the effects of outlying residences, infrastructure, and other compounding factors. The percentage of RBF within these concentric buffers, averaged for all communities of a FRZ, was compared against the percentage of RBF of the entire FRZ in which they were located. The analysis was also performed using an alternative fire zonation scheme, the homogeneous fire zones (HFZ)45. To investigate the sensitivity of this threshold, we repeated the analysis with a threshold of 20 (1998–2017) and 40 (1978–2017) years. The 20- and 40-year definitions of RBF yielded results coherent to those of the 30-year definition, suggesting that our results are not overly sensitive to the choice of age threshold  was disproportionately higher around our selected communities relative to the areas of the fire zones. Using the 5-km buffers, we compared the percentage area harvested near communities against percentage area harvested across FRZ for a 30-year period.We conducted several supplementary analyses to investigate whether other factors were related to the prevalence of RBF near communities, including ignition density, forest harvest percentage, and land cover. Ignition density was calculated within 5-km concentric buffers centered on our selected communities and compared to the ignition density outside of this buffered area, considering all fires larger than 0.1 ha from 1988–2017. We also verified if forest harvest from 1985–2015 , and deciduous forest, which is considered substantially less flammable than coniferous forests. The analysis of water was carried out using the Canada MODIS Land Cover Time SeriesFurther information on research design is available in the Supplementary InformationReporting Summary


PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase ABC (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates brain-derived neurotrophic factor (BDNF)-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase σ , receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ-deficient mice (PTPσ+/−). The antidepressant drug fluoxetine, which is known to promote TRKB phosphorylation and reopen critical period-like plasticity in the adult brain, disrupts the interaction between TRKB and PTPσ by binding to the transmembrane domain of TRKB. We propose that both chABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex by promoting TRKB signaling in PV+ neurons through inhibition of TRKB dephosphorylation by the PTPσ-CSPG complex.Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulfate proteoglycans (CSPGs), which preferentially encase parvalbumin-containing  by chondroitinase treatment, or by chronic antidepressant treatment. We now show that the effects of both chondroitinase and fluoxetine are mediated by the neurotrophin receptor TRKB in parvalbumin-containing (PV+) interneurons. We found that chondroitinase-induced visual cortical plasticity is dependent on TRKB in PV+ neurons. Protein tyrosine phosphatase σ , a receptor for PNNs, interacts with TRKB and inhibits its phosphorylation, and chondroitinase treatment or deletion of PTPσ increases TRKB phosphorylation. Antidepressant fluoxetine disrupts the interaction between TRKB and PTPσ, thereby increasing TRKB phosphorylation. Thus, juvenile-like plasticity induced by both chondroitinase and antidepressant treatment is mediated by TRKB activation in PV+ interneurons. Plasticity is the ability of the brain to change itself through establishing new neuronal connections and rewiring existing ones. Plasticity is prominent in early life and it peaks during so-called “critical periods” when the ability of the brain to adapt is at its highest . After t+) orchestrate synchronous neuronal oscillations and play a particularly important role in this process  around them  balance that take place because of maturation of cortical inhibitory interneurons. Fast-spiking interneurons expressing parvalbumin  might be a nexus that mediates plasticity processes induced by both methods. PTPσ is a receptor for CSPGs , and it + interneurons is essential for plasticity induced by chABC. While CSPGs removal by chABC injection into the visual cortex promotes ocular dominance shift, this effect is abolished in heterozygous mice with reduced TRKB in PV+ neurons (PV-TRKB+/−). We have confirmed that PTPσ interacts with TRKB, and genetic deficiency of PTPσ promotes TRKB phosphorylation (pTRKB) in vitro and in vivo. We further show that PTPσ deficiency promotes plasticity at network levels, as PTPσ+/− mice display critical period-like plasticity in the visual cortex in adulthood. Finally, we have observed that the antidepressant fluoxetine disrupts TRKB:PTPσ interaction in vitro and in vivo.We now demonstrate that TRKB activity in PVPTPRS gene (PTPσ+/− mice) and their wild-type (WT) littermates, C57BL/6J mice heterozygous for TRKB gene in PV+ interneurons (PV-TRKB+/−) and their PV-Cre littermates (PV-TRKB+/+), WT C57BL/6J mice were used in the experiments. BALB/c PTPσ+/− mice were originally developed by Michel Tremblay's lab  mice were generated by mating heterozygous floxed TRKB mice  littermates with intact TRKB in PV+ neurons were used as a control group for PV-TRKB+/− mice. The mice were four months old at the beginning of the experiments. WT C57BL/6J mice five months old were used to assess fluoxetine effect on TRKB:PTPσ interaction in the visual cortex in vivo. The mice were kept under standard laboratory conditions with 12/12 h light/dark cycle (lights on at 6 A.M.) and access to food and water ad libitum. All the procedures involving animals were done in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals guidelines and were approved by the Experimental Animal Ethical Committee of Southern Finland (ESAVI/10 300/04.10.07/2016).BALB/c and C57BL/6J mice heterozygous for 2. The death was confirmed by ascertaining cardiac and respiratory arrest. The animals were decapitated, the visual cortices were dissected and stored at −80°C. Samples from the primary visual cortex were sonicated in NP lysis buffer  containing a protease and phosphatase inhibitor mix  and 2 mm Na2VO3. The homogenate was centrifuged for 15 min at 15,000 × g, 4°C. The supernatant was collected and used for further analysis. Protein levels were measured using DC Protein Assay kit  by colorimetric Lowry method in Varioskan Flash (Thermo Fisher Scientific).Mice were killed with COin vitro (DIV). For the experiments assessing the effect of PTPσ genetic deficiency on pTRKB in vitro, cortical cell cultures were prepared from BALB/c mouse embryos  extracted on E18 using the same protocol as described above for the rat cells. Mouse fibroblast cells stably expressing full-length TRKB (MG87.TRKB) or TRKA (MG87.TRKA) were cultured in DMEM supplemented with 10% fetal calf serum (FCS), 1% penicillin/streptomycin (PS), 1% L-glutamine, and 400 mg/ml G418. Human-derived HEK293T cells were cultured in DMEM supplemented with 10% FCS, 1% PS, and 1% L-glutamine.Cerebral cortical cell cultures were prepared from Wistar rat (Harlan Labs) embryos extracted on embryonic day (E)18 . The celWe transfected 70% confluent MG87.TRKA, MG87.TRKB, and HEK293T cell lines using Lipofectamine 2000 (Thermo Fischer Scientific). MG87.TRKA and MG87.TRKB cells were transfected with PTPσ (RefSeq number NM_019140) Myc-DDK-tagged open-reading frame (ORF) plasmid purchased from OriGene (#RR209636), pCMV6-Entry vector with C-terminal Myc-DDK Tag (#PS100001) was used to transfect control cells. HEK293T were transfected with GFP-tagged full-length TRKB plasmid , PBS with Tween 20 (PBST) was used for ELISA .Aggrecan was purchased from Sigma-Aldrich (A1960). Anti-phospho-TRKA (Tyr490)/TRKB  rabbit monoclonal antibody (mAb) was purchased from Cell Signaling Technology . Anti-TRKB goat polyclonal antibody (pAb) was bought from R&D Systems, #AF1494. Anti-phosphotyrosine mouse monoclonal antibody (clone PY20) was purchased from Bio-Rad (#MCA2472). Anti-PTPσ (SS-8) mAb was purchased from Santa Cruz Biotechnology (SC-100419). Secondary horseradish peroxidase (HRP)-conjugated antibodies were purchased from Bio-Rad (goat anti-rabbit #1705046 and goat anti-mouse #1705047) and from Invitrogen (rabbit anti-goat #611620). Enhanced chemiluminescent (ECL) substrate WesternBright Quantum HRP substrate (Advansta) was used for Western blotting (#K-12042). Pierce HRP ECL substrate was used to detect luminescence in ELISA . Tris-buffered saline with Tween 20 (TBST) was used for Western blotting ; 20 ng/ml BDNF was added to cortical cells for 10 min; 0.1 and 1 μm sodium orthovanadate and protease inhibitor mix. The homogenized suspension was centrifuged , and the resulting supernatant was used for analysis. For immunoprecipitation, TRKB was captured using anti-TRKB antibodies (R&D Systems). The samples were incubated with Sepharose, washed with NP lysis buffer twice and the proteins were separated by heating in 2× Laemmli buffer  for 5 min at 95°C. The samples were loaded to NuPAGE 4–12% Bis-Tris Protein polyacrylamide gels , and the proteins were separated according to their molecular weight using electrophoresis. The samples were transferred to polyvinylidene difluoride (PVDF) membrane, incubated in 1:1000 primary antibody dilution in 3% bovine serum albumin (BSA) in tris-phosphate buffer containing 0.1% Tween 20 (TBST) overnight at 4°C and subsequently incubated in HRP-conjugated secondary antibodies  for 1 h at room temperature (RT). The bands were visualized using chemiluminescent western blotting substrate in Fuji LAS3000 camera (Tamro Medlabs).The cells were lysed using NP lysis buffer containing 2 mm sodium bicarbonate and 42.6 mm sodium carbonate, pH 9.8). On day 2, the plate was incubated for 2 h at RT in the blocking buffer (3% BSA in PBST) to block non-specific binding. Homogenized and centrifuged brain samples or lysed cell samples were added to the plate and incubated overnight at 4°C. On day 3, the plate was washed four times with PBST using an automated plate washer (Thermo Fisher Scientific Wellwash Versa), and the samples were incubated in anti-phosphotyrosine or anti-pTRKB antibodies diluted 1:1000 in the blocking buffer overnight at 4°C. On day 4, the samples were washed four times in PBST and incubated with tertiary HRP-conjugated antibodies in the blocking buffer (1:5000) at RT for 1 h. Finally, ECL was added to the plate and luminescence was measured with 1-s integration time using Varioskan Flash plate reader (Thermo Fisher Scientific). Levels of TRKB:PTPσ interaction were evaluated by ELISA using a similar protocol. TRKB was captured using anti-TRKB antibodies, and anti-PTPσ were applied afterward to assess levels of PTPσ bound to TRKB.Levels of pTRKB were evaluated using ELISA for pTRKB developed in our lab . On day Cell-surface ELISA was conducted to assess PTPσ levels found on the cell surface as previously described . BrieflyTransparent skull surgery was conducted as described previously . Animals+/− versus WT experiment and 7 d for the PV-TRKB+/− versus WT experiment. The integrity of the suture was checked on a daily basis before the lights were on.MD was conducted by suturing the eye contralateral to the imaged hemisphere (left eye) with perma-hand silk thread (Ethicon). The length of the MD was 3.5 d for the PTPσ2:air.Optical imaging of intrinsic signals was conducted as previously described . Visual Four-month-old mice were used for the experiments. During week 1, the animals underwent transparent skull surgery. After 7 d, during week 2, the animals underwent the first session of the optical imaging under isoflurane anesthesia (IOS1). During week 3, the animals were injected with 50 mU of chABC in PBS or PBS into the binocular area of the visual cortex and were subjected to MD for 7 d. During week 4, the eyes were opened, and IOS2 immediately took place.Two-month-old mice were used for the experiments. During week 1, the animals underwent transparent skull surgery. After 7 d, the animals underwent the first session of the optical imaging (IOS1) followed by MD for 3.5 d. We have switched to the shorter MD length as compared with the previously described experiment since it has been recently demonstrated to be sufficient for the induction of the critical period-like plasticity . On day The mice were anesthetized with isoflurane combined with 0.05 mg/kg buprenorphine analgesia. Images acquired during the first session of the optical imaging were used to identify the binocular area of the visual cortex. A hole in the skull was made with a drill, and 50 mU of chABC in 1 µl of PBS or 1 µl of PBS was injected in the center of the binocular area using a microsyringe pump; 10-µl Nanofil syringe (WPI Nanofil) with drilled 1.1-mm outlet bore to accommodate 1.0-mm glass needle and custom-made bevelled borosilicate glass needles with a 50-µm tip diameter were used for the infusions. Infusions were done at the speed of 2 nl/s. After the surgery, the animals were left to recover in the home cage, and the second imaging session took place 7 d later.in vivo fluoxetine experiment . Parametric tests were preferentially used to gain statistical power. Exceptions were made whenever the data presented lacked homoscedasticity or when variables were discrete, in which cases non-parametric tests were chosen. The statistical tests used in each particular experiment and statistical values are described in the legend of figures, and statistical values are provided in p < 0.05. Statistical analysis and plots were made in GraphPad Prism 6 software. Data are presented as mean ± SEM. Detailed information on the statistical analysis of each experiment, and number of samples/animals used is given in The experiments were designed taking into account good laboratory practices and the 3Rs principle of animal research. Both sexes of mice were used in all the experiments involving animal testing, except for the Digestion of PNNs by chABC is a well-known activator of plasticity , and it + interneurons is involved in chABC-induced plastic changes. For that purpose, we generated mice heterozygous for full-length TRKB allele in PV+ interneurons , as previously shown . These data demonstrate that chABC-mediated reactivation of visual cortical plasticity is dependent on intact TRKB signaling in the PV+ interneurons.We tested the hypothesis that TRKB functioning in PVly shown . Howeverin vitro (DIV) for 7 d with 2 U/ml chABC for 30 min and checked the activation of TRKB by assessing its phosphorylation levels .Next, we assessed whether PNN digestion with chABC induces TRKB activation in primary cerebral cortical neurons. We treated rat cortical neurons grown s pTRKB; . We obsein vitro B.in vitro); however, it significantly decreased BDNF-induced pTRKB (C). Taken together, these data demonstrate that PNNs regulate plasticity in a TRKB-dependent manner in vivo and that PNNs exert negative effects on TRKB activation in vitro.After observing that PNN digestion with chABC treatment positively affects pTRKB, we investigated whether treatment with aggrecan, a major PNN component in the adult CNS, might have an opposing effect on pTRKB and render BDNF-induced TRKB activation less effective. We added 10 µg/ml aggrecan to the primary cortical neurons cultured for 6 DIV. After 24 h, we challenged the cells with 20 ng/ml BDNF for 10 min. Aggrecan treatment did not alter basal pTRKB levels , were transfected with myc-PTPσ, immunoprecipitated with anti-TRKB antibody and blotted for PTPσ. In the transfected samples, we observed a band below 250 kDa (A), which is consistent with the predicted molecular weight of the plasmid's product. Additionally, a 165-kDa band was observed in non-transfected cells, which corresponds to the endogenous mature full-length PTPσ . Since transgenic mice quite often develop compensatory mechanisms to counteract genetic deficiency, we wanted to confirm that neurons lacking PTPRS allele would present comparable reduction in PTPσ:TRKB protein interaction. We prepared E18 neuronal cultures from cortex of WT or PTPσ+/− littermates, and compared them after 7 DIV using co-immunoprecipitation. We observed a reduction of ∼50% in the interaction between TRKB and PTPσ in samples from PTPσ+/− mice as compared with WT (B). Then, we further investigated whether PTPσ influences pTRKB. We compared cortical pTRKB levels in embryonic cultures from PTPσ−/− and PTPσ+/− mice with those in cultures prepared from their WT littermates. Notably, PTPσ had a clear gene dosage-dependent suppressive effect on the basal pTRKB. PTPσ+/− cortical cultures demonstrate increased pTRKB as compared with cultures from their WT littermates, and PTPσ−/− samples demonstrate yet further increased pTRKB significantly differing from both PTPσ+/− and WT samples (C). We also checked the levels of pTRKB in samples from the adult visual cortex of mice heterozygous for PTPRS gene (PTPσ+/−). In line with our in vitro data, adult PTPσ+/− mice exhibit increased basal TRKB autophosphorylation in the visual cortex (D), despite having slightly reduced levels of total TRKB (E), which may represent a compensatory downregulation because of a long-term increase in pTRKB.Next, we set out to investigate the role of PTPσ in pTRKB by using mice heterozygous for PTPσ , indicating that closure of the critical period was delayed or prevented in the PTPσ+/− mice.Finally, we investigated whether increased TRKB signaling produced by genetic deficiency of PTPσ might render the cortical structures of PTPσ+/− mice F, indica+ interneurons in the amygdala and hippocampus, shifting PV+ interneurons toward an immature state and reopening brain plasticity (m) for 30 min. Fluoxetine dose-dependently reduced the interaction between TRKB and PTPσ in vitro as measured by ELISA (A). Since fluoxetine has been shown to increase pTRKB as fast as 30 min after systemic injection  and killed the animals 30 min after the injection. Acute fluoxetine treatment significantly reduced TRKB:PTPσ interaction in vivo (B).Antidepressants have been demonstrated to induce activation of TRKB receptors in the brain . Moreoveasticity . Therefoby ELISA A. Since njection , we chec in vivo B.C). These data indicate that fluoxetine does not affect PTPσ shedding and positioning on cell surface, and supports the idea that the decrease in PTPσ levels in co-IP experiments is a result of decreased interaction with TRKB.PTPσ is proteolytically processed by cleavage in the juxtamembrane region, leading to shedding of the extracellular domain . To ruleFig. 3m) failed to influence TRKB:PTPσ interaction in the cells carrying R427A/Y433F mutated TRKB (D), providing evidence that the site of interaction of PTPσ and fluoxetine with TRKB lies within the transmembrane region of TRKB.Antidepressants have recently been shown to directly interact with TRKB through the transmembrane region . Moreoveted TRKB D, provid+ interneurons. PNNs, extracellular structures rich in CSPGs, are associated with a reduction of plasticity in the adult brain. Maturation of PNNs coincides with the closure of the critical period  and in samples from the visual cortex of PTPσ+/− mice. Moreover, we observed that genetic deficiency of PTPσ delays the closure of critical period-like plasticity in the adult visual cortex, an effect that we demonstrated to be dependent on TRKB in PV+ neurons.CSPGs, major components of PNNs, have been shown to exert inhibitory action on plasticity through protein tyrosine phosphatase receptor type S . PTPσ ha with WT . Interes with WT . Faux et with WT . We have+ interneurons is sufficient for the induction of juvenile-like plasticity in the adult brain and necessary for the plasticity-inducing effects of fluoxetine (TRKB signaling is known to be critical for activation of plasticity by antidepressant drug treatment and for the behavioral consequences of it . Moreoveuoxetine . We now uoxetine . These dAntidepressants have recently been shown to directly interact with TRKB through its transmembrane domain . Our dat+ neurons, which releases TRKB from the PTPσ-mediated dephosphorylation and promotes its autophosphorylation. Chondroitinase treatment downregulates CSPG-mediated activation of PTPσ, which allows for enhanced signaling of TRKB (Our findings suggest a general mechanism responsible for the opening of critical period-like plasticity in the adult brain by chABC and antidepressant treatment . We prop of TRKB . Antidep of TRKB .+ interneurons is a critical regulator of chABC-induced and antidepressant-induced plasticity in the adult cortex. The similarity in the plasticity-promoting effects of chABC and antidepressants prompted us to focus on these two treatments, but there are a number of other methods known to reactivate juvenile-like plasticity in the adult cortex (+ interneurons.Taken together, our data reveal that interaction between TRKB and PTPσ in PVt cortex , such ast cortex , 2014 ant cortex . It will


Since the discovery of TAR DNA-binding protein 43 (TDP-43) in 1995, our understanding of its role continues to expand as research progresses. In particular, its role in the pathogenesis of Alzheimer’s disease (AD) has drawn increasing interest in recent years. TDP-43 may participate in various pathogenic mechanisms underlying AD, such as amyloid β deposition, tau hyperphosphorylation, mitochondrial dysfunction, and neuroinflammation. Because AD is complex and heterogeneous, and because of the distinct characteristics of TDP-43, mostly seen in the oldest-old and those with more severe clinical phenotype, subcategorization based on specific features or biomarkers may significantly improve diagnosis and treatment. AD-like cognitive dysfunction associated with TDP-43 pathology may therefore be a distinct encephalopathy, referred to as limbic-predominant age-related TDP-43 encephalopathy (LATE). TAR DNA-binding protein 43 (TDP-43) is a 414-amino-acid protein encoded by the TAR DNA binding protein gene on chromosome 1p36  and amyotrophic lateral sclerosis (ALS). Similar findings were found in AD: pathological TDP-43 aggregation is more common in the limbic system of patients with AD, including the hippocampus, amygdala, and adjacent cortex , is a major component of senile plaques and is considered to be a major pathological change in AD , a significant contributor to disease (Gao et al., Mitochondria are organelles that can replicate independently in a variety of eukaryotic cells. They provide energy and also participate in nearly all types of cell death, including apoptosis and necrosis, and contribute to a number of important physiological functions (Kroemer et al., Neuroinflammation, characterized by microglial activation, astrocyte proliferation, and increased cytokine expression, is a key factor in the pathogenesis of AD. While acute inflammation protects the nervous system, chronic inflammation can contribute to AD development (Youmans and Wolozin, Many studies have demonstrated the importance of TDP-43 in the pathogenesis of AD (Amador-Ortiz et al., The AD-like cognitive dysfunction associated with TDP-43 pathology may represent a distinct encephalopathy because of its specific characteristics. Many researchers believe that the disease caused by TDP-43, characterized by changes in cognitive function, may be a novel disease: LATE (Nelson et al., Since the shorthand for the disease is LATE, the interesting question that could be asked is: is it too late to discover LATE? Most clinical trials for treatment of AD have failed (Doody et al., TDP-43 plays an important role in the CNS. Abnormal aggregation and localization of TDP-43 can cause mitochondrial dysfunction, aggravate neuroinflammation, and contribute to many diseases involving various regions of the brain. Abnormalities in TDP-43 in the upper and lower motor neurons can contribute to ALS, while abnormalities in TDP-43 in the frontal and temporal lobes can contribute to FTLD, and those in the limbic system to AD. TDP-43 contributes to various pathogenic processes underlying AD, such as Aβ deposition, tau hyperphosphorylation, mitochondrial dysfunction, and neuroinflammation. However, AD-like cognitive dysfunction associated with TDP-43 pathology appears to be distinct from that associated with AD. Therefore, AD-like cognitive dysfunction with TDP-43 as the main marker may be defined as a new encephalopathy, LATE, or may alternatively represent a subcategory of AD . Future WH and YZ contributed equally to this work and wrote the manuscript. WH, YZ, LT, ZB, JH, NH and YL contributed to the critical revision of the manuscript and read and approved the submitted version.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.


To design efficient and powerful field emission cathodes, the screening effect is of great importance and should be traded off between screening and emitter number. It has long been found that to achieve maximum emission efficiency in an array, neighboring emitters are at two or three times their height from each other. However, this is only true for one-dimensional emitters, such as carbon nanotubes, but for graphene, a two-dimensional material, it is different. In this work, we found that to achieve maximum emission efficiency in an array of graphene, the separation of the emitter is four times the height, and it is insensitive to the anode voltage and the distance between the cathode and the anode. Field emitter arrays (FEAs) have been an active area of research for many years due to the high current densities, low voltage operation, and high pulse repetition that can be obtained ,3,4,5,6.Although much research has been done on the EFS, most of it has been based on the EFS from carbon nanotubes (CNT) arrays in simulations. For example, in 2000, Nilsson et al. found that an optimum intertube distance of two times the height of the CNT is strongest in accordance with the experiment . HoweverGraphene is a monolayer of carbon atoms packed into a dense honeycomb crystal structure that can be viewed as an individual atomic plane extracted from graphite . The atoIn this paper, we simulated the field screening effect in graphene arrays, and the effects of various parameters in the model on the field screening effect were investigated in detail. We also compared the simulated current density of the graphene sheet array that we optimized with some previous experimental results about field emission of graphene arrays prepared by different methods.l and thickness 2r are placed on a grounded cathode that is separated from the positive anode by distance d; the graphene is separated by a distance s, the anode voltage is U. Assuming that the thickness and height of the graphene in the array are the same and the top of the graphene sheet is assumed to be circular. The emitted current depends on the electric field in the vicinity of the graphene top. The emission array performance was studied by simulating a unit cell consisting of the integrated flake nanostructure and the anode.Because the radius of the curvature of the tip of the emitter is very small on the nanometer scale, and the device structure is relatively large, the skills of variable mesh are used. The accurate field strength at the tip of the emitter is obtained from denser grids, and sparse grids are used far from the emitter to speed up the program. Calculations were performed using the MAGIC software code. MAGIC is a particle-in-cell simulation code, which is a two-dimensional, finite-difference, time-domain code for the self-consistent simulation of the interaction between charged particles and electromagnetic fields. The full set of Maxwell equations and the complete Lorentz force equation were used. Space charge effects were automatically included. Boundary conditions included conductors, the surface of graphite nanoplatelets, and the cell-to-cell relationships using SYMMETRY MIRROR boundary conditions, which allowed us to simulate an entire array, not just a cell as in many previous works. J is calculated froms/l.A Fowler-Nordheim emission module was developed and inserted in MAGIC code to model the electron field emission from the surface. The current density Although the skill of variable grid is used to achieve simulation of the field emission characteristics of emitters with nanometer-scale thickness, because the thickness of graphene is an atomic scale and the total number of grids that MAGIC can draw is limited, even the skill of variable grid cannot simulate the electric field at the top of the emitter of the graphene sheet. Therefore, we firstly studied the effect of the thickness of graphite nanoplatelets to the screening effects; graphite nanoplatelet is a kind of graphite sheet with nanometer thickness, graphene is actually a graphite sheet with only one or more atomic layers. In the simulation, we changed the spacings between the graphite nanoplatelets in arrays with different thicknesses. s/l. The result shows that the law of change of electric field strength at the tip of the graphite nanoplatelet in the middle of the array caused by the field screening effect is insensitive to the thickness of the graphite nanoplatelets; the three curves are approximately coincident. All show that the electric field strength at the top of the emitter increases with the increase of the spacing of the array. For s/l > 5, the value of the normalization of the electric field strength reaches saturation. So, we focused on studying the effect of different spacings between the graphite nanoplatelets and the screening effects of graphite nanoplatelets arrays. Simulation with different thicknesses of graphite nanosheet arrays had almost no effect on the results; thus we used graphite nanosheets  instead of graphene to simulate.s/l = 0.5, there is almost no potential distribution around the top of the emitter. When s/l = 4, the interaction between emitters is very small, and the electric potential distribution is similar to that of a single emitter.We simulated the potential distribution of single platelets and graphene arrays with different spacings; the anode voltage was 400 V. s/l = 4 and U = 200 V.Because the field emission current is exponentially related to the electric field intensity at the top of the emitter, the emission current of the emitter at the center of the array is also simulated by a particle simulation method. U = 400 V and r = 20 nm. The current of graphite nanoplatelets in the middle of the array increases with the increase of spacing between graphite nanoplatelets; for s/l > 5, the value of current of graphite nanoplatelets in the middle of the array reaches saturation. The result demonstrates that with the increase of the spacing between graphite nanoplatelets, the screening effects decrease, the electric field strength increases, the current of graphite nanoplatelets in the array tends to be saturated, and the behavior of the individual graphite nanoplatelet is similar to that of a single one. Therefore, we can weaken the screening effects and increase the current of each emitter of the array by changing the spacing between emitters in the array.Although the emission of a single emitter is not affected by the screening effects, the current of a single emitter is limited, which cannot meet the requirements of the device. According to the above simulated calculation, for graphene arrays, the screening effects can be neglected when the spacing between emitters is five times higher; on the other hand, due to the enlargement of the spacing between emitters, the number of emitters on a fixed area decreases and the total current on the surface decreases. Because the spacing between emitters is very close, the screening effects will affect the value of the current of each emitter in the array, which makes the total emitter current smaller. Therefore, it is necessary to find the appropriate array density by simulated calculation.Z-axis depth is 1 m in the MAGIC simulation software, the actual fixed area obtained is 10 square centimeters. We assumed that the current of each graphite nanoplatelet in the array is equal. When the spacing of graphite nanoplatelets in the array is twice the height of the emitter, the number of emitters on the area is 500, when the spacing of graphite nanoplatelets in the array is three times the height of the emitter, the number of emitters on the area is 333, and so on. The number of emitters on the launching surface decreases with the increase of the spacing of emitters, and then the total emission current of all emitters on the launching surface is calculated.So, we performed further simulation for a total array width of 1 mm. Because the default 2 as a function of the normalization spacing, for the aspect r  chosen to be 20 nm, 40 nm, and 80 nm, when the spacing of the graphite nanoplatelet between the array is four times the height of the graphite nanoplatelet, the total emission current of the emitter surface is the largest, and the law is the same for different thicknesses of graphite nanoplatelet. This also corroborates the results of previous simulations that if we focus on studying the effect of different spacings between graphite nanoplatelets and the screening effects of graphite nanoplatelets arrays, the results are insensitive to different thicknesses of graphite nanoplatelets. Therefore, in the later simulation, we still used graphite nanoplatelets with a thickness of 40 nm (r = 20 nm), instead of graphene sheets. On a fixed area of the emitter, the number of emitters on the emitter surface is determined by the distance between the emitters. The more the number of emitters on the emitter surface, the greater the emission current on the fixed area. However, the greater the number of emitters, the smaller the distance between emitters, and the more obvious the field screening effect becomes. In order to obtain the maximum field emission current on a fixed area, it is necessary to find a balance between the distance and the number of emitters. s/l = 4 is the equilibrium in our simulations.Firstly, the anode voltage was 200 V, we used a graphite nanoplatelet array with different thicknesses and changed the spacing between the graphite nanoplatelets in the array, then calculated the total current in this area. r = 20 nm); we changed the spacings between the graphite nanoplatelets in the array with different anode voltages and calculated the total emission current of the area. 2 as a function of the normalization spacing, for the anode voltage is chosen to be 150 V, 175 V, and 200 V. When the spacing of the graphite nanoplatelets in the array is four times the height of graphite nanoplatelets, the total emission current of the emitter surface is the largest, and the law is insensitive to anode voltages.The thickness of the graphite sheet was 40 nm  graphite nanosheets instead of graphene to simulate. We found that when the spacing between the graphene in the graphene array is five times the height of the graphene, the screening effect is greatly weakened. The current of graphene emitters in the array tends to be saturated, and the behavior of each individual graphite nanoplatelet is similar to that of a single one. We also found that when the spacing between the graphene in the graphene array is 4 times the height of the graphene, the total emission current of the emitter surface is the largest, and the law is insensitive to the anode voltage and the distance between cathode and anode. The emission current density of graphene arrays optimized by our simulation is better than in most previous experimental results about field emission of graphene array cathodes, the results of this simulation can provide guidance for the design of graphene array cathode emitters.In this paper, calculations were performed using the MAGIC software code, and the technique of variable mesh was used. We focused on the effect of different spacings between graphite nanoplatelets to study the screening effects of graphite nanoplatelets arrays. Simulations show that different thicknesses of graphite nanosheets in arrays have almost no effect on the results. Therefore, we used thicker (40 nm thickness,


The results show that the resistance of the sensors exhibited significant changes with increasing humidity, the response times of the two sensors within the relative humidity range of 23–97% were 49 s and 67 s, and the recovery times were 24 s and 43 s, respectively. Meanwhile, continuous breathing monitoring results indicate that the sensitivity of the sensors remained basically unchanged during 10 min of normal breathing and simulated apnea. The response of the sensor is still good after 30 days of use. We believe that the Schottky structure composite sensor is a very promising technology for human breathing monitoring.Two types of Schottky structure sensors (silicon nanowire (SiNW)/ZnO/reduced graphene oxide (rGO) and SiNW/TiO Sleep apnea hypopnea syndrome (SAHS) is a prevalent and potentially serious disorder with the occurrence of at least 30 apneas during normal 7-hour sleep, where each apnea time is at least 10 s . Therefo2) nanomaterials can also be used as moisture-sensitive components [2 was proposed as the sensitive layer of a humidity sensor, and Milad Ghalamboran reported TiO2–SnO2 composites for moisture detection [2/rGO Schottky composite metal nanomaterials were developed and used for sensitive detection of trace explosive vapors [With the rapid development of science and technology, more and more new materials have been developed for humidity-sensitive sensors in recent years, and composite nanomaterials have become a focus for research, including one-dimensional carbon, silicon, and semiconductor nanoparticles ,4. As a mponents  screen-petection . In addietection ,11,12,13etection ,15. The etection . Inspiree vapors ,18, and 2/rGO, which combine the advantages of graphene and metal oxide. We found that the resistance of the three-dimensional compound materials is sensitive to humidity, and the high sensitivity, fast response time, and excellent repeatability of the sensors provide high potential and very good prospects for the design of a portable human breathing monitoring system.In this paper, we report two kinds of Schottky structure humidity sensors, SiNW/ZnO/rGO and SiNW/TiO4 which had been stored in the refrigerator, quickly injected it into a sealed bottle filled with ice, sealed the bottom with deionized water, and quickly shook it until the ice melted. We immersed the SiNW array into the TiCl4 solution to obtain a TiO2-modified SiNW array [The design process of the Schottky structure sensor is shown in NW array ,22. FinaNW array ,24. 2 nanoparticles. It can be seen from the figure that the surface of the SiNWs was successfully decorated with TiO2 nanoparticles. 2/rGO Schottky heterojunction, and the inset is a side screenshot. The successful formation of the Schottky heterostructure involves a large number of defects on the surface, resulting in a significant increase in activity and improving the amount of water absorption. Because the doped TiO2 is relatively small, the existence of TiO2 cannot be directly seen in 2 nanoparticles. In 2. −1 and 1592 cm−1, corresponding to the D and G peaks, respectively. After reduction of graphene, both the D and G peaks shifted downward. I(D)/I(G) is the intensity ratio of the D-peak and G-peak, the D-peak represents defects in the C atom lattice, and the G-peak represents the in-plane expansion and contraction of C atom sp2 hybrid vibration. The I(D)/I(G) value of rGO (1.12) is clearly greater than that of GO (0.91), revealing the formation of new sp2.Scanning electron microscopy  was used to check the surface morphology of the prepared sensor. The surface properties were studied by X-ray photoelectron spectroscopy . The structural characteristics of the sensor were characterized by Raman scanning spectroscopy . 3COOK, K2CO3, NaCl, and K2SO4  at room temperature to simulate environmental relative humidity levels of 23%, 43%, 75%, and 97%, as shown in We used a classic saturated salt solution method to test the sensitivity of the developed sensors at different humidity levels ,26. Firs0 is the initial value of the sensor under dry conditions. The response time and recovery time of the sensor were defined as the time it takes for the resistance of the sensor to change from the initial value to 90% of the stable offset.The sensor was secured to the Printed Circuit Board (PCB) with conductive silver slurry, and copper wire electrodes were placed at both ends of the circuit board. The experimental data acquisition was performed using a miniature hardware terminal based on an STM32F030 microcontroller , which was controlled by an Android phone connected via Bluetooth. The resistance values were obtained by the voltage-divider circuit, and were collected and plotted on the phone after filtering and smoothing . As shown in 2/rGO were 49 s and 67 s, and the recovery times were 24 s and 43 s, respectively; the response and recovery times of SiNW/ZnO/rGO were better than those of SiNW/TiO2/rGO. For respiratory monitoring, SiNW/ZnO/rGO sensors are more suitable for human respiratory monitoring because of their faster response and better sensitivity. In short, these sensors based on Schottky structures have great potential for the development of future portable respiratory monitoring systems, and they also have certain implications for the development of new moisture-sensitive materials.In summary, we presented two Schottky structure sensors and demonstrated their good sensitivity and good repeatability in human breathing monitoring. The response times of SiNW/ZnO/rGO and SiNW/TiO


The propagation length of the hybrid plasmonic waveguide varies from 0.14 μm to 20.43 μm by the voltage tunability of graphene in 1550 nm incident light. A modulator with a length of 3 μm is designed based on the hybrid waveguide and it achieves about 100% modulation depth. The lower energy loss (~1.71 fJ/bit) and larger 3 dB bandwidth (~83.91 GHz) are attractive for its application in a photoelectric integration field. In addition, the excellent robustness (error of modulation effects lower than 8.84%) is practical in the fabrication process. Most importantly, by using the method of adjusting propagation length, other types of graphene modulators can also achieve about 100% modulation depth. A modulator is the core of many optoelectronic applications such as communication and sensing. However, a traditional modulator can hardly reach high modulation depth. In order to achieve the higher modulation depth, a graphene electro-optical switch modulator is proposed by adjusting propagation length in the near infrared band. The switch modulator is designed based on a hybrid plasmonic waveguide structure, which is comprised of an SiO F) with electrostatic gating. Based on this excellent tunability of the absorption property   ,38, whereff/A0 can be given by Equation (3) [m refers to the total energy density and max {W} represents the maximum energy density of the structure. Smaller Aeff/A0 means stronger optical confinement in the devices. The consumed energy can be given by E = 1/4CVp2. C represents the total capacitance of the modulator, which is mainly composed of the quantum capacitance of graphene and the equivalent capacitance between graphene and Si. Vp refers to the peak-to-peak value of external voltage. The 3dB bandwidth of the modulator can be given by f3dB = 1/2πτRC = 1/2πRtotalC, where Rtotal refers to the resistance of the whole modulator. It is composed of the graphene resistance and the contact resistance between graphene and metal electrode. The resistance of graphene can be generally ignored because of the small value (about tens of ohms) [The normalized effective mode area Ation (3) :A0=λ2/4of ohms) .2 at 1550 nm incident wavelength are − 129 + 3.3i, 2.25 and 12.25, respectively [The modal properties of the presented modulator are investigated numerically by using the finite element method package in RF module of COMSOL Multiphysics 5.4 software . The modectively .In order to optimize the size of modulator, the normalized effective mode area and propagation length need to be calculated. By discussing the values of the normalized effective mode area and propagation, the optimal size of gap g and radius R can be decided.eff/A0 becomes larger with the increase of g. The main reason is that when g is large, the interface area between dielectric Si and Ag nanowire is not large enough to confine the light into a very small scale. The Lm becomes larger with the increase of g. The main reason is that the increase of g can bring the smaller interface area between dielectric Si and Ag nanowire, which will decrease the energy loss of incident light and bring the increase of Lm. m will increase with the larger R. The key factor is that the larger radius will cause a smaller loss of incident light and improve the propagation length. By contrast, larger R reduces the degree of light localization and results in a larger Aeff/A0. In fact, the results shows that larger Lm and smaller Aeff/A0 are contradictory in the devices. In order to obtain the larger Lm and keep Aeff/A0 as small as possible, the g is set to 1 nm and R is set to 50 nm. By tuning the refractive index of graphene, Neff will be changed and the propagation length can be adjusted for this switch modulator.It can be concluded from According to the result in p2, the energy loss of the whole switch modulator is ~1.71 fJ/bit. The total resistance mainly includes graphene resistance and the contact resistance between graphene and metal electrode. Because the resistance of graphene is too small (about tens of ohms) and can be ignored, the total resistance is 177.93 ohms. According to Equation f3dB = 1/2πτRC = 1/2πRtotalC, the 3 dB bandwidth of this switch modulator is 83.91 GHz.The total capacitance is mainly composed of graphene quantum capacitance and equivalent capacitance between graphene and Si. After calculation, the quantum capacitance of graphene is ~0.098 F/m and the equivalent capacitance between graphene and Si is ~0.0108 F/m. Due to the width and length of this switch modulator is 400 nm and 3 μm, its total capacitance is 10.66 fF. Moreover, 1.5 V and 2.3 V voltages are used to control the on and off for this switch modulator. According to Equation E = 1/4CVm) − min(Lm))/max(Lm). The maximum error of this switch modulator in 1.5 V is about 2.89% (g = 1 corresponds to the ~19.926 μm propagation length and g = 4 corresponds the ~20.502 μm propagation length). For the error of propagation length in 2.3 V, maximum error of this switch modulator is about 0.58% (g = 1 corresponds to the ~0.1396 μm propagation length and g = 4 corresponds to the ~0.1404 μm propagation length). As shown in It can be observed from 2. 10 nm thickness of Si upon the graphene layer is deposited as the substrate by atomic layer deposition, which can constrain the electric field distribution inside the device. Another layer of graphene can be transferred in the same way. Then, a SiO2 layer can be transferred onto graphene, which can be used as a cladding material for the gap between Ag and the upper graphene. In addition, the SiO2 layer is also used to grow a silver nanowire. Flipping the entire structure, by ion beam etching an SiO2 layer in a z direction definite size, a cylindrical hole can be etched out. After using the magnetron sputtering technology and masks technology, silver ions can fill empty slots in the cylinder to form the silver nanowire needed. Finally, flipping the entire structure to the original place, SiO2 cladding can be grown on the whole devices [The switch modulator can be manufactured with general commercial SOI wafers. Firstly, two grating couplers can be produced at both ends of the device by deep reactive ion etching (The cycle of grating couplers is set to 780 nm in 1550 nm working length), which can achieve the phase matching and let the incident light enter or output the switch modulator. Then a layer of graphene can be transferred onto 100 nm SiO devices ,42. In tIn this paper, a novel graphene electro-optical switch modulator based on adjusting propagation length is proposed in the near infrared band. It successfully combines the advantages of hybrid waveguide and the tunability of graphene to adjust the propagation length, which achieves ~100% modulation depth for the switch modulator in theory. The numerical simulations at the wavelength of 1550 nm show that GESMBOSN has relatively low loss (~1.71 fJ/bit) and very large 3 dB bandwidth (~83.91 GHz). In addition, the wonderful robustness of this switch modulator is also conducive to the actual application. Most importantly, with this new method to design a graphene switch modulator, other graphene switch modulators can also have the potential to arrive at about 100% modulation depth.


The thinning of thick Si substrate down to 50 µm has been performed prior to a multi-step milling of the conical-shaped micropore with final pore size of 3 µm. A transfer of graphene onto the fabricated conical-shaped micropore with little or no defect was successfully achieved using a newly developed all-dry transfer method. A circular shape graphene nanohole with diameter of about 30 nm was successfully obtained at beam exposure time of 0.1 s. This study opens a breakthrough in fabricating an integrated graphene nanohole and conical-shaped Si micropore structure for biosensor applications. A biosensor formed by a combination of silicon (Si) micropore and graphene nanohole technology is expected to act as a promising device structure to interrogate single molecule biopolymers, such as deoxyribonucleic acid (DNA). This paper reports a novel technique of using a focused ion beam (FIB) as a tool for direct fabrication of both conical-shaped micropore in Si Biosensors have attracted a great deal of attention for biological detection in the past three decades ; for exaGraphene, a two-dimensional nanomaterial, facilitated with a nanohole and integrated onto a solid-state micropore structure is considered as a promising alternative to realize a stable biosensor due to its one-atom thick layer and its extremely high surface-to-volume ratio, which enable it to be used as a highly sensitive membrane for the detection of biomaterials, such as DNA and protein ,21,22,23At first, the Si substrate (thickness: 525 µm) was cleaned with conventional organic treatment  water) to remove native oxides and contaminants on the substrate surface. 3N4) was deposited onto a Si substrate with a thickness of 100 nm using plasma-enhanced chemical vapor deposition (PECVD), as shown in I, were set at 2.1 and 9.3 nA for primary and secondary milling, while the ion beam voltage, V, was kept constant at 30 kV. It can be seen here that the primary milling was performed in a multistep manner where the milling diameter was changed at every milling step, as the upper diameter is always set larger than the bottom diameter so that the conical-shape of the micropore can be realized. At the primary milling, the diameter was changed in the condition that can be expressed as d1 > d2 > d3 >….> dn. The milling diameter was changed from 40 down to 15 µm, with the 5 µm in difference. Each milling step was carried out at the same depth value, zp, which is about 3 µm in depth. At the secondary milling stage, the milling was carried out in a single step. The value for ds and zs were always fixed to 3 and 1000 µm, respectively. The substrate with the micropore structure was characterized using scanning electron microscopy (SEM). Silicon nitride  and Raman spectroscopy (Witec Alpha 300 M+).I, of 9.3 and 2.1 nA, respectively. As shown in the For the results, first we present the dependency of the Si micropore’s shape and size with the change of the FIB milling current. Then, the dependency of the shape and size of the graphene nanohole as a function of the FIB milling time is described. The properties of the transferred graphene membrane on the Si micropore using the all-dry transfer technique is also presented. −1 and 2690 cm−1, respectively [2D/IG of 1.1 indicates that the transferred graphene layer is a bilayer graphene [−1, which indicates that clean and defect free graphene was successfully transferred by the all-dry transfer method.ectively . The intgraphene . No defeThe formation of the nanohole was performed in the transferred graphene on the Si micropore by a direct milling using the FIB. The Raman spectra was measured to confirm the nanohole formation in the graphene layer. In summary, a simple and reliable direct fabrication of a conical-shaped Si micropore and a graphene nanohole using a FIB was successfully demonstrated for the first time. A clean and defect free graphene was also successfully transferred accurately onto a micropore by a developed all-dry transfer method. This study opens a breakthrough towards the utilization of integrated graphene nanohole and conical-shaped Si micropore for biosensor applications.


The reactive nature of PE-ALD enables deposition of thin (2 nm) dielectrics directly on graphene and other two-dimensional materials without the need for a seed or functionalization layer; however, this also leads to significant oxidation of the graphene layer as observed by Raman. In FETs, we find this oxidation destroys conductivity in the graphene channel. By transferring thin (1.6 nm) MOCVD BN layers on top of graphene channels prior to PE-ALD, the graphene is protected from oxidation enabling BN/Al2O3 layers as thin as 4 nm. Raman and X-ray photoelectron spectroscopy on BN films show no significant oxidation caused by PE-ALD of Al2O3. Inserting the BN layer creates an atomically abrupt interface significantly reducing interface charges between the graphene and Al2O3 as compared to use of a 2 nm Al buffer layer. This results in a much smaller Dirac voltage (− 1 V) and hysteresis (0.9 V) when compared to FETs with the Al layer (VDirac = − 6.1 V and hysteresis = 2.9 V).Here, we investigate the use of few-layer metal organic chemical vapor deposition (MOCVD) grown BN as a two-dimensional buffer layer for plasma enhanced atomic layer deposition (PE-ALD) of Al The layered structure of these materials, with strong in-plane bonding and weak van der Waals inter-planar bonding, provides the ability to thin and stabilize them down to a single layer. Although, these materials have fully compensated surfaces with no dangling bonds; they are quite sensitive to the surrounding environment, including the substrate, ambient adsorbates, and in devices, the addition of component layers like-contacts, gate dielectrics, and passivation layers10. These can lead to oxidation, doping, and charge scattering severely degrading properties. In graphene, the effects of these surrounding elements have been shown to greatly impact basic transport properties and devices performance. To mitigate the effects of the substrate and adsorbates, a thin van der Waals (vdW) buffer layer, like hBN12, has shown to be extremely effective at preserving the properties of graphene.Devices based on two-dimensional (2D) materials offer great possibilities for applications requiring mechanical flexibility15; for which, atomic layer deposition (ALD) is ideally suited. However, 2D materials present a significant challenge to depositing ultra-thin, high quality, high-κ dielectrics due to the inherent lack of reactive surface nucleation sites16. To overcome these nucleation challenges, various surface functionalization and seeding layers have been used to promote ALD deposition. Surface functionalization by treatment with reactive species like ozone17, XeF218, and H2, O2, or N2 plasma21 produce functional surface groups and defects that provide nucleation sites. However, these functionalization methods partially convert sp2 C bonds in graphene to sp3 degrading properties, which can be in some cases recovered through annealing19. Nucleation can also be improved by functionalization with physisorbed molecules like H2O22 and NO223 followed by low temperature thermal ALD. Zheng et al.22 found the low temperature Al2O3 ALD layer to be low density and have low dielectric constant requiring deposition of a second higher temperature high quality layer. On the other hand, seeding-layers consisting of thin polymers24, metal-oxides26, or metals27 can be deposited by low impact methods, like evaporation, that minimize damage to the graphene layer. Functionalizing the graphene surface or inserting a seed layer between graphene and the ALD dielectric can introduce interfacial charges and traps, reduce the total dielectric constant of the gate stack, and limit the minimum equivalent oxide thickness (EOT)28. One alternative is to use a 2D buffer layer on top of the graphene to protect the interface during ALD30.The progression toward high performance 2D devices necessitates the integration with high quality thin dielectrics, for gates, tunneling barriers, etc.2O3 on graphene for top gated field effect transistors (FETs). PE-ALD offers a number of advantages over thermal ALD for deposition of dielectrics on 2D materials. Generally, the high reactivity of the plasma species allows for a wider range of materials to be produced, with higher quality, higher density, and at lower temperatures than thermal ALD31. Plasma species can also modify the surface promoting nucleation and greatly reducing nucleation delay critical for reducing gate thickness32. Additionally, PE-ALD enables more exotic coating and high-k dielectric that can reduce (EOT) even further33. For graphene and other 2D materials the plasma species can serve as in-situ functionalization eliminating the need for ex-situ functionalization or seeding required for thermal ALD of ultra-thin high quality layers; however, this occurs at the cost of damaging the 2D layer34. By transferring a thin (1.6 nm) BN layer on top of the graphene FET channel prior to PE-ALD of the Al2O3 gate dielectric, we demonstrate a weakly interacting 2D buffer layer that protects the graphene layer during PE-ALD. We find that depositing directly on graphene with no seed layer causes significant oxidation destroying the graphene channel, while devices with a BN buffer layer are preserved. These BN devices also have significantly lower shift in the Dirac point and lower hysteresis due to reduced interfacial doping at the BN/graphene vdW interface.In this paper, we investigate the use of 2D BN grown by metal organic chemical vapor deposition (MOCVD) as a thin buffer layer for plasma enhanced (PE) ALD of Al2O3 gate dielectric, Fig. 2O3 were explored: (1) no seed layer—PE-ALD directly on graphene, (2) transferred 2D BN on graphene followed by PE-ALD, (3) 2 nm e-beam evaporated Al seed layer followed by PE-ALD, and (4) transferred 2D BN layer followed by 2 nm e-beam evaporated Al seed layer and PE-ALD. Figure 2-plasma etching followed by e-beam deposition of Ti/Pt/Au ohmic contacts. An O2 plasma power of 200 W was used to selectively remove the graphene, while leaving the BN layer intact. For devices with the 2D BN layer a 1.6 nm thick BN layer was wet transferred on top of the defined graphene channel and contacts. BN layers were grown on 2″ sapphire wafers by MOCVD under self-terminating growth conductions, similar to the BN layer used on the substrates side, providing a large-area, highly reproducible and uniform 1.6 nm thick layer36. Figure 2/Si. After, the BN is transferred, the PMMA is removed, and the stack annealed to improve the graphene BN interface and clean the BN surface prior to ALD. Next, a 2 nm Al seed layer, excluded in buffer layer 1 and 2, is deposited followed by 20 nm of Al2O3 by PE-ALD and Ti/Au gate contacts.Top-gated graphene FETs were fabricated on chemical vapor deposition (CVD) graphene films transferred to 2″ MOCVD grown BN on sapphire substrates. A variety of FETs with gate lengths from 2.5 to 10 µm were used to investigate electrical characteristics of devices with different buffer layers for PE-ALD Al2O3 deposition on graphene’s structural quality. Figure 2O3 deposition. To compare the effect of the 2 nm Al layer, the graphene film was masked and Al was deposited on half of the sample. Compared to the as transferred spectra, the half without the Al layer shows a significant increase in defect related D/D’ peaks and reduction in the G’ indicative of the formation of graphene oxide37. The side with the 2 nm Al layer does not have the same increase in D and D’ indicating the layer serves to protect the graphene. AFM images  and morphology. Both layers appear to completely cover the graphene layer with no signs of nucleation issues, which is expected due to the in-situ functionalization caused by the O2 plasma.The advantages of PE-ALDs in-situ auto functionalization comes at the consequence of potentially damaging the graphene layer. Raman spectroscopy was used to investigate the effect of Alges Fig.  of Al2O32O3 gate dielectrics were deposited with no seed layer and the other half with the Al seed layer. Device characteristics were measured on one device with a 10 µm gate length per reticle. Figure D in the range of 0.7–2.1 mA/mm at Vds of 0.1 V. The oxidation observed in Raman clearly has a significant effect on the electrical conductivity of the graphene layer.To investigate the effect on device operation, a full 2 × 150 µm) graphene FET wafer was processed, in ~ half of the devices the Al × 150 µm35. To mitigate these interface effects we explore inserting a few layer thick sp2 bonded BN layer between the graphene and Al2O3 layer. Figure 2O3. BN is well established as an oxidation resistant coating even when thinned to only a few monolayers38, but how MOCVD/CVD grown films react to O2 plasma during PE-ALD is not established. AFM shows a uniform surface morphology with a roughness of ~ 0.5 nm  and N 1 s ( 397.8 eV) in good agreement with previous reports on sp2 bonded BN39 with no oxide related peaks around 193 eV (B–O)40. The lack of oxidation signatures in the BN layer indicates the BN layer could be thinned to below four mono-layers. With the established stability of the BN layers under the PE-ALD process, we now investigate its use as a buffer layer for protecting graphene. Figure 2O3 on bare graphene and graphene covered with the BN buffer. As observed in Fig. 2O3 oxidizes the graphene layer, but by covering the graphene with a thin BN layer the graphene is preserved with little change in the Raman. This can even be observed optically  structures from each region  from vdPs with the BN buffer, Al seed layer, and both the BN and Al seed layer of − 9 × 1011, − 3 × 1012, and − 7 × 1012 cm-2 and Hall mobility of 890, 560, 1,060 cm2/Vs. To check that the buffer type does not impact the gate leakage current (IG), we measure IG as VG is swept from − 8 to 4 V at Vds of 0.5 V. Figure G for all gate types, between 12 and 16 pA, demonstrating consistent insulating behavior of the gate dielectric independent of buffer type.To compare the effect of the 4 buffer types on FET performance, we fabricated a full wafer with top gates fabricated using each type, Fig. Dirac due to n-type doping and similar peak transconductance of 30 µS or better. Upon the reverse VG sweep, hysteresis with a positive shift in VDirac is observed in Ids–VG, which is common in graphene FETs. This shift is due to negative charge traps at the graphene interface from defects in the dielectric and/or contamination 43. The effect of interface contamination can be reduced by processing under vacuum or inert environments, cleaning processes, annealing, or by inserting a 2D buffer layer, like BN. Indeed, if we compare transfer curves from each buffer type, we observe VDirac and hysteresis depend strongly on the buffer type with the lowest doping and hysteresis in devices with a BN buffer  at 20 °C for up to 2hrs. Released films were wet transferred, dried in air, followed by the PMMA removal with acetone, and finally annealed in 5% H2:N2 forming gas at 400 °C for 30 min. Graphene grown on copper by CVD using methane as the carbon source were transferred to the BN/sapphire substrates using a typical wet transfer with PMMA, similar to the process described in Ref.44.Boron Nitride on 2″ sapphire substrates and transferred films used in this study were grown by metalorganic chemical vapor deposition (MOCVD) at 1,000 °C, 20 Torr and B/N ratio of 2250 for 30 minThe surface morphologies of graphene and BN layers were analyzed by AFM using a Bruker Dimension Icon in tapping mode. Raman measurements of graphene and BN were performed using a Renishaw inVia system under a backscattering geometry. A 488 nm excitation source at 4 mW, 20 µm slits, and a 3,000 l/mm grating was used for these measurements. Chemical analysis of films was performed using X-ray photoelectron spectroscopy .2-plasma. Source and drain Ti/Pt/Au contacts were evaporated. A 20-nm thick Al2O3 top gate dielectric was deposited by ALD. ALD was performed at 250 °C with half cycles of trimethylaluminum and a remote 300 W oxygen plasma, achieving a growth rate of 0.94 A/cycle. Gate metal (Ti/Au) contacts were defined using a second lift-off process31. The automated electronic characterization was performed using a Cascade Summit 12 k probe station with an HP 4142 parameter analyzer and GSG probes.Graphene FETs were fabricated using transferred CVD graphene on BN/sapphire. The graphene mesas were etched using an OSupplementary Information.


Here, we succeed in stabilizing pure-phase ε-Fe2C nanocrystals by confining them into graphene layers and obtain an iron-time yield of 1258 μmolCO gFe−1s−1 under realistic FT synthesis conditions, one order of magnitude higher than that of the conventional carbon-supported Fe catalyst. The ε-Fe2C@graphene catalyst is stable at least for 400 h under high-temperature conditions. Density functional theory (DFT) calculations reveal the feasible formation of ε-Fe2C by carburization of α-Fe precursor through interfacial interactions of ε-Fe2C@graphene. This work provides a promising strategy to design highly active and stable Fe-based FT catalysts.The development of efficient catalysts for Fischer–Tropsch (FT) synthesis, a core reaction in the utilization of non-petroleum carbon resources to supply energy and chemicals, has attracted much recent attention. ε-Iron carbide (ε-Fe 2C has been identified as the highly active phase for Fischer-Tropsch synthesis (FTS), but is stable only at low-temperature. Here, the authors show that ε-Fe2C phase can be stabilized even at ~ 573 K by being encapsulated inside graphene layers, and retains high activity in FTS.ε-Fe Because FT synthesis is a core reaction in the utilization of various non-petroleum carbon sources  to supply energy and chemicals, the development of efficient FT catalysts has received much-renewed interest in recent years6. Iron-based catalysts have widely been used in the industrial FT process because of the low cost of iron, wide operation conditions, and flexible product distributions7. However, Fe-based catalysts usually suffer from low activity and stability3, and thus many recent fundamental studies have been devoted to enhancing the FT activity and stability of Fe catalysts by employing different modifiers or different supports14. Unlike Ru- or Co-based FT catalysts, where metallic Ru0 or Co0 functions as the active phase, metallic Fe0 is unstable and the evolution of a conventional Fe-based catalyst typically results in a mixture of different iron phases including Fe3O4 and iron carbides under FT reaction conditions21. Iron carbides are believed to be responsible for the activation of CO and the chain growth in FT synthesis, but the nature of the true active iron-carbide phase is still under debate and this hinders the rational design of highly active and stable Fe-based FT catalysts.Fischer–Tropsch (FT) synthesis transforms syngas  FT reaction29. The Fe catalyst based on ε-Fe2C phase could also decrease the CO2 selectivity during FT synthesis30. However, it is known that ε-Fe2C would be transformed into χ-Fe5C2 at above 523 K, and thus would be unstable at a higher temperature (~573 K) that is usually adopted for Fe-catalyzed FT synthesis. Under FT reaction, Fe-based catalysts are usually coated with an amorphous carbon/carbide layer that facilely induces the carbides transformation  can stabilize this metastable phase for FT synthesis at 523–613 K. The Fe-time yield (FTY), which is defined as the moles of CO converted to hydrocarbons per gram of Fe per second, reaches 1258 μmolCO gFe−1 s−1 at 613 K, breaking the upper-limit value (1000 μmolCO gFe−1 s−1) reported for Fe-based FT catalysts13. The catalyst is highly stable under our FT reaction conditions and high CO conversion (~ 95%) can be kept at 573 K at least for 400 h. DFT calculations suggest that the confinement effects of graphene layers favor the formation of ε-Fe2C from carburization of α-Fe, which maintains the high stability of ε-Fe2C under high-temperature FT reaction conditions. On the other hand, the facile transformation of FexC particles may occur during FT synthesis over the conventional FT catalyst. To the best of our knowledge, this is the first example to demonstrate experimentally that the ε-Fe2C phase can be stabilized under high-temperature FT reaction conditions. The present work provides a promising strategy to synthesize highly active and stable Fe-based FT catalysts and offers an opportunity for the study of FT reactions on pure metastable-phase iron carbides.Here, we attempt to replace the amorphous carbon with few graphene layers that confines the Fe-based catalyst. The confinement of the rigid geometry of the graphene shell can inhibit the formation of the amorphous carbon layer and improve the stability of highly active ε-Fe2C Fig. . We repo2 and carburization in syngas flow. X-ray diffraction (XRD) measurements and 57Fe Mössbauer spectroscopy showed that θ-Fe3C was the major Fe phase in the precursor obtained after pyrolysis  facet of θ-Fe3C and the (002) facet of graphene, respectively, were observed . It is of interest that ε-iron carbide (ε-Fe2C) rather than θ-Fe3C or χ-Fe5C2 was formed after the carburization  on the 2D material overlayers, which mainly follow the defect-aided intercalation mechanism34. In addition, the Raman spectra of ε-Fe2C@graphene catalyst show that the 2D peak position of ε-Fe2C@graphene blueshifted relative to single-layer graphene and the peak pattern consistent to the few graphene layers rather than bulk graphite , the ε-Fe2C content remained constant (about 62.8%), indicating the stabilizing effect by the graphic carbon layer on ε-Fe2C even under reaction conditions  as explained in the computational details of 2C inside graphene layers can keep it from phase transformations probably.To gain further insights into the possible evolution of iron phases, we have performed in situ XRD characterizations for our sample in syngas flow under different conditions. α-Fe was still the major phase under syngas with a H3 K Fig. . In addi3 K Fig. . It is n3C@graphene samples before and after treatment under different conditions  and the G-band (graphene carbon), respectively . The θ-Fe3C@graphene , indicating unique defect-rich structure graphene layers after the annealing process. Moreover, the XPS results clearly confirmed the presence of defective graphene layers during the reducing and carburization processes  of ε-Fe2C is ~6–10 times higher than the θ-Fe3C and 2 times higher than the χ-Fe5C2. Furthermore, CO-TPD profiles of ε-Fe2C@graphene catalyst show a multi-peak overlapped cure with a maximum peak position at ca. 843 K, which is attributed to desorption of CO after recombination of dissociated carbon and oxygen on the surface  under the same reaction condition. On the other hand, the FTY value of reference Fe/C catalysts decreased sharply upon increasing Fe loading probably due to the aggregation of Fe species and the oxidation of the active carbide phase under reaction conditions  was increased to 160 L gcat−1 h−1 at 613 K  with different GHSVs revealed that the ε-Fe2C@graphene is much more active than χ-Fe5C2 in FT synthesis, as shown in Supplementary Fig. 2C@graphene was completed during 50 h at GHSV of 64.0 L gcat−1 h−1. For evaluation of catalyst deactivation, we have performed long-termed FT reactions for both ε-Fe2C@graphene and un-encapsulated χ-Fe5C2 catalysts at 573 K under harsh conditions . Further, the pressure drop across the ε-Fe2C@graphene catalyst bed was negligible even at high conversion, indicating that the coke deposition on this catalyst was significantly suppressed by the graphene layers under harsh condition.Time-on-steam evolution of CO conversion for ε-Feons Fig. . The CO 2C@graphene catalyst follows the Anderson-Schulz-Flory distribution  is relevant in describing the thermodynamics of iron carbides, which can be determined from the equilibrium of carburization reactions of different gas atmospheres for pretreatment or FT reaction at some temperatures and pressures. Higher temperature and lower pressure, as well as higher H2/CO ratio, result in lower ΔμC value indicating a lower carburization ability  can be derived for describing the carburization reaction from metallic Fe to iron carbide. The volume-normalized carbon absorption energy (Ωabs) was applied to the bulk iron carbides20.The effects of a graphene layer on the surface stability and carburization feasibility of ε-Feity Fig. . Based oωabs), which is suitable for describing the surface carburization of iron carbide with and without graphene confinement. The most abundant (101), (1-21), and (2-21) surfaces were selected to evaluate the confinement effects of graphene layers on the ωabs  > (1-21) > (2-21) according to the calculated surface energy  show similar results to those of graphene.On the other hand, the confinement effects are modeled by covering the ε-Fe3 Å Fig.  close to2C surface with and without graphene confinement. Both the direct and H-assisted dissociations are considered including different active sites of perfect ε-Fe2C, graphene, and the C-vacancy on ε-Fe2C  of ca. 1.2 eV than those of direct and H-assisted dissociations (2.57-2.61 and 2.83-2.87 eV) on the perfect ε-Fe2C surface with and without the confinement of graphene. The CO dissociation on the graphene site hardly occurs due to the high Ea values (> 2.89 eV). Similar results can be found for graphene-N. The confinement of graphene or graphene(-N) favors to improve the stability of the highly active ε-Fe2C to achieve the high catalytic performance of FT at high temperature.In addition, taking (1-21) as an example, we further investigate the mechanism of CO dissociation on the ε-Fe2C nanocrystals for the FT reaction. It exhibited remarkably activity (~ 1258 μmolCO gFe−1 s−1) and stability (>400 h) under realistic FT synthesis conditions. The confinement effects of graphene layers stabilize the metastable but very active ε-Fe2C phase. The unique confinement structure (ε-Fe2C@graphene) can inhibit the formation of an amorphous carbon layer that converts catalytically active ε-Fe2C phase to other less active carbide phases . Our results and conclusion could help in the rational design of promising active phases in industrial catalysts for hydrogenation processes.In summary, we synthesized graphene layers encapsulated ε-Fe3)3•9H2O. In a typical synthesis, an amount of Fe(NO3)3•9H2O, corresponding to the final Fe loading of 30–60 wt%, was mixed with 5.0 g urea and 3.0 g glucose at 393–433 K to form a transparent solution. The resultant molten mixture was heated at 453 K in an oven for 24 h. The solid collected was subjected to a heat treatment in flowing N2 (10 mL min−1) at 673 K for 30 min and finally at the final temperatures (773–1023 K) for another 2 h.The iron carbide nanocomposites were synthesized by pyrolysis of a molten mixture of urea, glucose, and Fe(NO3C@graphene samples obtained above were reduced in a flow of 3 L gcat−1 h−1 of H2 at 623 K for 3 h (denoted as Fe@graphene), and then the carbonization in a flow of 64 L gcat−1 h−1 of syngas (H2/CO = 1) at 573 K for 10~400 h (denoted as ε-Fe2C@graphene).The θ-FeThe size and morphology of samples were determined using a FEI Tecnai G20 transmission electron microscope operated at 200 kV and a Hitachi SU8000 field emission scanning electron microscope at an accelerating voltage of 15 kV.57Fe Mössbauer measurements were performed at room temperature or 77 K using a conventional spectrometer  in transmission geometry with constant acceleration mode. A 57 Co(Rh) source with an activity of 25 mCi was used. The velocity calibration was done with a room temperature α-Fe absorber. The spectra were fitted by the software Recoil using Lorentzian Multiplet Analysis. The samples were passivated in flowing 1% O2/N2 for 1 h at room temperature prior to air exposure and being sealed in a sample holder with paraffin wax for Mössbauer spectroscopy measurements.The 2/CO = 1) at 573 K for 5 h. Subsequently, the adsorbed species were removed by flowing He at 823 K for 2 h. The samples were cooled to 308 K, then CO chemisorption experiment was conducted. The average CO:Fe stoichiometry was assumed 1:2. For θ-Fe3C@graphene catalyst, reduction and carburization processes are eliminated.The CO chemisorption was performed using a Micromeritics AutoChem II 2920 unit. Before CO chemisorption, 0.1 g of catalyst was reduced under flowing pure hydrogen at 623 K for 3 h and then carburized in syngas (H2/CO = 1) at 573 K for 5 h. Subsequently, the adsorbed species were removed by flowing He at 573 K for 2 h. The samples were cooled to 308 K. At this temperature, the carburized sample was flushed with CO for 1 h and consequently purged with He until the baseline of CO signal leveled off. Finally, the sample was heated to 1,073 K at a ramp of 10 K min−1. For θ-Fe3C@graphene catalyst, reduction and carburization processes are eliminated.For CO temperature-programmed desorption (CO-TPD), 0.1 g of catalyst was reduced under flowing pure hydrogen at 623 K for 3 h and then carburized in syngas (HX-ray diffraction (XRD) patterns of the samples were recorded on a Bruker D8 powder diffractometer equipped with a Cu-Kα source operated at 40 kV and 40 mA and a Vantec-1 detector.Kα radiation operated under vacuum (2 × 10−6 Pa) with the binding energy (BE) calibrated using the C 1s peak at 284.6 eV.X-ray photoelectron spectroscopy (XPS) measurements were conducted on a VG Multilab 2000 photoelectron spectrometer using Al −1) with a ramping rate of 10 K min−1.Thermogravimetric analysis (TGA) was carried out on a NETZSCH TG 209F3 TGA analyzer during temperature ramping from 303 K to 1,173 K in flowing air (50 mL min2 (10 mL min−1) at 623 K for 3 h before reactions. The pre-treated catalysts were cooled to 373 K in flowing H2 before the introduction of syngas (H2/CO = 1). The reaction temperature was then ramped slowly to 593 K. The permanent gases  and light alkanes  in the effluent of the reactor were monitored by an online Agilent Micro GC3000A gas chromatograph (GC) equipped with the molecular sieve, Plot-Q and Al2O3 capillary columns and a TCD detector. The oil and wax products were separated using a cold trap (271 K) and a hot trap (423 K), respectively, while the aqueous products were obtained by phase separation in those traps. The oil products were analyzed using an Agilent 6890N GC with a FID detector and a HP-5 column; the wax products were dissolved in CS2 and analyzed using an Agilent 7890A GC equipped with a FID detector and a HT5 column; the aqueous fraction was analyzed using an Agilent 4890 GC equipped with a FID detector and a HP-Innowax column. The product selectivity was calculated based on the carbon balance.Fischer–Tropsch synthesis was performed in a stainless steel fixed-bed reactor (i.d. = 12 mm). Catalysts were diluted with inert SiC particles in a mass ratio of 1:10 prior to testing. The diluted catalysts (5.5 g) were pre-treated in flowing H44 and projector-augmented wave (PAW) method45 as implemented in the Vienna ab initio simulation package (VASP)46. A second-order Methfessel–Paxton electron smearing scheme (sigma = 0.2 eV) was used because of the metallic conductor properties of iron carbide. Plane-wave kinetic energy cut off of 400 eV is sufficiently accurate for the spin polarization calculations of the electronic properties of open-shell iron carbide. Energy and force convergence criteria were 10−5 eV and 0.03 eV Å−1, respectively. The most abundant ε-Fe2C(1-21), ε-Fe2C(101), and ε-Fe2C(2-21) surfaces were taken into account. A vacuum of 15 Å was used for screening the interactions vertical to the surface. The most stable configurations were selected to model the confinement effects of graphene and N-doped graphene (graphene-N) on the carburization feasibility of ε-Fe2C from metallic iron and the reaction mechanism of CO dissociation. The computational details are deposited in Density functional theory calculations were performed using the generalized gradient approximation Perdew–Burke– Ernzerhof of (PBE) functionalSupplementary Information