Here, it is shown that epitaxial graphene films grown on SiC can increase the hardness of SiC up to 100% at low loads (up to 900 µN), and up to 30% at high loads (10 mN). By using a Berkovich diamond indenter and nanoindentation experiments, it is demonstrated that the 30% increase in hardness is present even for indentations depths of 175 nm, almost three hundred times larger than the graphene film thickness. The experiments also show that the yield point of SiC increases up to 77% when the SiC surface is coated with epitaxial graphene. These improved mechanical properties are explained with the formation of diamene under the indenter's pressure.Silicon carbide (SiC) is one of the hardest known materials. Its exceptional mechanical properties combined with its high thermal conductivity make it a very attractive material for a variety of technological applications. Recently, it is discovered that two‐layer epitaxial graphene films on SiC can undergo a pressure activated phase transition into a sp 2) ‐diamene (sp3) phase transition. The hardness of graphene coated SiC increases by 30% compared to bare SiC, even for indentation depths 300 times larger than the graphene coating thickness.This work shows that the yield point of SiC can be increased by 77% by coating SiC with epitaxial graphene. This enhancement is due to a pressure‐induced graphene (sp However, experiments on graphene grown by chemical vapor deposition (CVD) on a copper substrate showed no increase in hardness of the graphene coated copper substrate. Regarding the stiffness of substrates coated with graphene, no increase has been detected for exfoliated graphene on SiO2 substrates, while a 5% increase has been measured for copper coated with CVD compared to bare copper. For a copper substrate coated with graphene, a mild increase in bearing capacity has been shown during the initial elastic regime at low loads.Graphene has shown great potential for mechanical applications due to its exceptional mechanical properties.4, 52 to sp3 hybridization. This phase transition dramatically changes the elastic properties of the graphene/SiC system under pressure. In particular, purely elastic ångström indentation (Å‐indentation) measurements indicated a surface stiffness comparable to diamond, while no investigations on the plastic behavior have been performed.Very recently it has been reported that two‐layer epitaxial graphene grown on silicon carbide (SiC) can undergo a room temperature, pressure activated phase transition from sppressure.11 In  due to its extreme hardness, strength, and high thermal conductivity. Considering the technological interest in the exceptional mechanical properties of SiC, second only to diamond, here, we investigate how the hardness of a SiC substrate can be further improved when SiC is coated with an atomically thin and thermally conductive epitaxial graphene film. In particular, we conduct Berkovich hardness indentation tests on monolayer (1L) epitaxial graphene films grown on the Si‐face of SiC(0001), where a typical buffer carbon layer (BfL) sits in between graphene and SiC  substrates are investigated by indentation experiments using a Hysitron TI 950 Triboindenter with a diamond Berkovich indenter, applying loads in the range between 300 µN and 10 mN  direction using a Berkovich indenter. In Figure  induced by the pressure activated sp2 to sp3 phase transition in the two graphitic layers under the indenter. This 2D diamond‐like structure on SiC increases the resistance of SiC to yield compared to bare SiC, resulting in higher hardness. On the other hand, previous theoretical work predicts no graphene‐diamene phase transition at room temperature for >3 L. Indeed, we find that when SiC is coated with 10 L of epitaxial graphene, the hardness decreases of ≈88% compared to bare SiC. This is also in agreement with previous studies that did not show any improvement in the hardness of copper when coated with only one layer of CVD graphene. The increased hardness of the 1L/Bfl/SiC(0001) system is consistent with a coating harder than the SiC substrate. The hardness of the graphene/SiC composite structure decreases with increasing loads, reaching a plateau value of ≈40 GPa at 10 mN loads, a value which is 30% larger than the hardness of bare SiC at the same load and closer to the hardness of diamond, i.e., 60–150 GPa. Furthermore, compared to bare SiC, the hardness of 1L/Bfl/SiC(0001) and 2L/H‐SiC(0001) at lower loads, e.g. 500 µN, displays an incredible increase of up to 100%, compared to bare SiC, reaching values of 60 GPa , and 63% for the AFM nanoindentation experiment (10 nm).Furthermore, we investigate the presence of residual indentations at low loads (300–700 µN) on the surface of bare SiC(0001) and graphene coated SiC to determine the onset of plastic deformation. Interestingly, we observe residual indentations on the surface of bare SiC for all loads, while no residual indentations are present on the surface of 1L/Bfl/SiC at loads 300 and 400 µN  probe to apply a local load and simultaneously measure the electronic current flowing through the AFM tip‐sample contact, see 33 diamene structure, we have investigated the hardness of single crystal SiC coated with epitaxial graphene films. We find that when SiC is coated with 10L of epitaxial graphene, the hardness decreases of ≈88% compared to bare SiC. However, when SiC is coated with a 1 L epitaxial graphene plus a graphene‐like buffer layer, or two graphene layers (in this case the SiC surface is passivated with hydrogen), we observe a dramatic increase in hardness. Precisely, we observe that coating SiC with 1L graphene plus buffer layer can increase the hardness of up to 100% at low loads (between 500 and 900 µN) compared to bare SiC, increasing from 30 to 60 GPa, a value approaching the hardness of diamond. This increase in hardness falls off at high loads, reaching a plateau value of 30% at 10 mN. The experiments also show that the yield point and onset of plastic deformations in SiC increases up to 77% when the SiC surface is coated with epitaxial graphene. These findings shed light on the formation of diamene under the indenter's pressure. In particular, we show that the atomically thin diamene layer can improve hardness of SiC even at high loads, corresponding to indentations of ≈175 nm, i.e., almost 300 times larger than the graphene film thickness. This work opens new possibilities for designing ultra‐hard and ultra‐light thermally conductive coatings for SiC to improve its mechanical performances for applications such as body armors, high‐impact protective coatings, and for use in aeronautics, aerospace, and automobile industry.In conclusion, motivated by the recent discovery of a room temperature pressure activated phase transition of epitaxial graphene into a sp4 The first carbon layer on the Si‐face of SiC is called the buffer layer and this layer is partially covalently bonded to the SiC surface (≈30% sp3 bonded carbon atoms). The layers on top of the buffer layer have carbon atoms in sp2 configuration. Therefore, when we refer to single layer graphene, it is a structure comprised of a graphene layer and buffer layer. The quasi‐free standing bilayer graphene is prepared from single layer epitaxial graphene sample by intercalation in hydrogen atmosphere at an approximate pressure of 1000 mbar with hydrogen flow at 3.0 slph. Hydrogen atoms saturate Si—C bonds between SiC surface and buffer layer, which create Si—H bonds and turn sp3 bonded carbon atoms into sp2 configuration. More details about the growth procedure can be found in Reference. Schemes of the structures are presented in Figure Large area epitaxial graphene films are grown on the Si face of 6H silicon carbide (0001) substrates (II–VI Inc) by the thermal decomposition method.14 TheRtip, is ≈150 nm at room temperature and in humid atmosphere. The Berkovich tip indents the sample surface at a constant rate until the set maximum load is achieved, then is held for 5 s. The loading time for this process is 62 s. Finally, the tip is unloaded linearly in time within 5 s  byHere  We therefore use the following equation to describe the projected areaAt large contact depths the ideal tip area function, mentioned in Equation 29 We 0C kept at 24.56, describing the ideal Berkovich diamond indenter.The parameters in Equation S is defined as S = dP/dh, which can be obtained from the unloading part of a load‐displacement curve as shown in Figures Er isβ is a correction factor =1.034 for a Berkovich tip. The reduced elastic modulus is given byEi= 1140 GPa and νi= 0.07 are the known elastic modulus and Poisson's ratio of the indenter, and E and ν are the same parameters of the sample.Contact stiffness −1) in ambient conditions. The normal forces between 0 and 200 µN are used to indent a sample's surface. The investigated area is scanned before and after indentation experiment with the same tip in a tapping mode, to distinguish if the residual indentation was created or not.The AFM nanoindentation experiments are performed on a Bruker Multimode 8 AFM using a diamond AFM probe  in ambient conditions. The current dependency on normal load is measured at forces between 0 and 250 nN.The conductive AFM measurements are performed with a Bruker Multimode 8 AFM using a sharp conductive diamond probe (Adama innovation, tip radius ≈10 nm, normal spring constant 74 N mThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.


The in vivo experiment further demonstrated the distribution of targeted NPs in tumor tissues, with changes in NIRF and MR signals observed. Our study indicated that SPIO-aPD-L1-Cy5.5 NPs can be used to monitor PD-L1 expression in breast cancer as NIRF/MR contrast agents.Chemotherapy has remained the mainstay of treatment of triple-negative breast cancer; however, it is significantly limited by the associated side effects. PD-1/PD-L1 immune checkpoint inhibition therapy (ICI) has been a breakthrough for this patient population in recent years. PD-L1 expression is crucial in immunotherapy since it is a major predictor of PD-1/PD-L1 antibody response, emphasizing the significance of monitoring PD-L1 expression. Nonetheless, it is hard to assess the expression of PD-L1 before surgery, which has highlighted the urgency for a precise and noninvasive approach. Herein, we prepared a dual-mode imaging nanoparticle probe to detect PD-L1. The particle size, zeta potential, biocompatibility, and imaging ability of NPs were characterized. The synthesized NPs showed slight cytotoxicity and good T2 relaxivity. The targeted NPs accumulated more in 4T1 cells than nontargeted NPs  Triple-negative breast cancer (TNBC) is a subtype of breast cancer negative for PR/HR/Her-2 receptors, accounting for 10–20% of breast cancers. It has been established that TNBC exhibits a highly aggressive phenotype accounting for its poor prognosis . PD-1/PDαvβ3 [Molecular imaging enables noninvasive monitoring of changes in potential molecular targets of tumor cells. In recent years, contrast agents have been developed to detect tumors and improve treatment efficacy, involving recognizing specific receptors on the surface of tumor cells, such as αvβ3 , 10 and αvβ3 , 12, whiαvβ3 , 14. In αvβ3 , 16. Intαvβ3 , 18 and αvβ3 , 20.3+ as the signal unit, SPIO has some upsides. (1) The signal intensity of SPIO is higher than Gd chelate contrast agents at the same concentration. (2) SPIO absorption by the body is accompanied by efficient biodegradation and iron homeostasis mechanisms for treating the free irons [Superparamagnetic iron oxide (SPIO) nanoparticles are among the highest-ranked nanoparticles in medicine due to their unique physicochemical property (superparamagnetism) as well as their established biocompatibility and stability in aqueous solutions , 22. Moree irons , and thaee irons . Therefo3O4 and NHS-Cy5.5 to form stable amide linkages. Take 20 mg solution of PEG-COOH-coated Fe3O4 , replace the buffer with 0.02 M MES solution, and adjust the pH to 5.5. Then, 2 mg PD-L1 antibody (clone 10F.9G2) or IgG antibody (for the control group) was added, and the mixture was incubated at 26°C for 30 min in a shaker. Subsequently, 4 mg EDC was added to the mixture and incubated overnight in a shaker at 26°C. The solution was removed, and a magnetic separation column was used to remove the free antibody and rinse out the stagnant magnetic beads. 1 ml of the solution was treated at a time, and the obtained colorless solution was then measured. NHS-Cy5.5 was dissolved in anhydrous DMF and diluted to a 20 mg/mL solution. The magnetic beads were taken after coupling the PD-L1 antibody, and the volume was made to 10 mL. The NHS-Cy5.5 solution was added to the mixture and incubated at 26°C for 5 h in a shaker. The free Cy5.5 was removed using a 100 K ultrafiltration tube  until a clear colorless solution was observed. The volume of the product was made to 20 mL at a concentration of 1 mg/ml.Free amino groups of antibody IgG and anti-PD-L1 can react with the active group of PEG-COOH-coated FeThe nanostructure of the nanoparticles was determined by a transmission electron microscope . The zeta potential and size of the nanoparticles were studied by dynamic light scattering using a Zetasizer Nano ZS . The emission and excitation spectra were recorded by a fluorescence spectrometer .3 cells/well density and cultured overnight. The adherent cells were then incubated with 100 μL of the corresponding medium containing SPIO-aPD-L1-Cy5.5 of various Fe concentrations  for 24 h. Subsequently, the cells were washed three times with PBS, and then, 90 μL of fresh medium and 10 μL of CCK8 reagent were added. The 96-well plates were then incubated at a constant temperature for 2 h. In addition, a blank group (only add the 90 μL of fresh medium and 10 μL of CCK8 reagent) was set up. A microplate reader was used to record the absorbance at a wavelength of 450 nm. The cell viability was calculated using the following formula:Ae is the absorbance of the experimental well, Ac is the absorbance of the control well, and Ab is the absorbance of the blank well. The experiment was repeated three times.The CCK-8 method was used to examine the cytotoxicity of the molecular probe on 4T1 cells. The 4T1 cells were seeded in a 96-well plate at a 5 × 105 cells/mL overnight. Then, the cells were incubated with SPIO-aPD-L1-Cy5.5 NPs  at pH 7.4 for 4 h, and SPIO-IgG-Cy5.5 NPs were used as controls. To further validate the active targeting of the nanoparticles, a blocking group was made, which was designed to add antibody PD-L1  before adding SPIO-aPD-L1-Cy5.5. After the incubation, the cells were then washed three times in PBS, and DAPI was used to stain the nuclei for 10 minutes. Fluorescence images were acquired by confocal laser scanning microscopy .To evaluate the cellular uptake of the nanoparticles, 4T1 cells were seeded onto 35 mm glass-bottom culture dishes  at a density of 1 × 106 cells in 200 μL.All experiments followed animal ethics of the guiding opinions on the treatment of laboratory animals issued. All female Balb/c nude mice (aged 4 weeks) were obtained from the Experimental Animal Center of Guangxi Medical University. 4T1 cells were injected subcutaneously in the right flank at a concentration of 2 × 10MRI exams of SPIO-aPD-L1-Cy5.5 NPs were processed by a 3.0TMR  with a mouse coil . SPIO-aPD-L1-Cy5.5 NPs range 0–0.714 mg/ml Fe concentrations were dissolved in pure water, added to 1.5 ml EP tubes, and then scanned. T2-weighted MRI was performed for each tube using a fast spin-echo (FSE) sequence .in vivo MRI and NIRF, the nude mice were divided into two groups (consisting of 3 mice), including the experimental and control groups. All mice were scanned twice, before injection and 6 h after injection of 0.1 ml NPs into the tail vein, and the dose of Fe was 2 mg/kg. The fluorescent images were photographed by a fluorescence imaging system  . During imaging, mice were exposed to a 2% isoflurane and oxygen gas mixture and maintained under anesthesia. Relative signal intensity (RSI) was defined as the ratio of tumor to muscle signal and used to assess NPs targeting ability.For μm sectioning. Also, sections were stained with Prussian blue to visualize the accumulation of NPs.After the imaging, the mice were euthanized, and the tumor was collected. All tissues were fixed with 10% formalin. Subsequently, tumor specimens of the two groups were removed and paraffin-embedded for 4-3 , and the concentrations of Fe were determined using ICP-MS. The amount of Fe was shown as mg/kg tissue.This part uses Du's  method. in vivo toxicity of the NPs by observing the presence of damage within the sections by H&E staining. Blank Balb/c nude mice (aged 4 weeks) were divided into 2 groups (n = 3), and SPIO-aPD-L1-Cy5.5 and SPIO-IgG-Cy5.5 were injected. After 24 h, mice were sacrificed, and their hearts, livers, spleens, lungs, and kidneys were harvested. The obtained sections were stained with H&E staining, which helps us see if there is tissue damage.We monitored the x ± s). Independent samples t-test was performed using SPSS 23.0 software to compare RSI and Fe concentration between the SPIO-aPD-L1-Cy5.5 group and SPIO-IgG-Cy5.5 group. The statistical significance of the difference was expressed as p < 0.05.Each group of data was obtained by repeating three times and expressed as mean ± standard deviation  (We estimated the ely 50%) . AccordiA confocal laser scanning microscope (CLSM) was used to view the cellular uptake of the SPIO-aPD-L1-Cy5.5.4T1 cells treated with SPIO-aPD-L1-Cy5.5 displayed noticeable red fluorescence enhancement in the membrane. And blocking group demonstrated significantly reduced fluorescence signal. As a control, cells treated with SPIO-IgG-Cy5.5 showed significantly lower red fluorescence signals. And the results of the blocking and control groups indicated that the PD-L1 targeting strategy effectively enhanced the uptake of SPIO-aPD-L1-Cy5.5 by 4T1 cells .−1 mM−1. These results suggested that SPIO-aPD-L1-Cy5.5 could be applied as a sensitive MRI T2 contrast agent to visualize the in vivo drug delivery process.We used T2-weighted MR imaging to determine the T2-weighted relaxivity  for the MRI potential of SPIO-aPD-L1-Cy5.5. From in vivo contrast by intravenous injection of SPIO-aPD-L1-Cy5.5 NPs in 4T1-bearing mice. The T2 signals at the tumor sites were darker 6h after injection. In addition, we analyzed the relative signal intensity (RSI) between the two groups (preinjection and postinjection). The results suggested that the preinjection and postinjection RSI in the targeted group was 2.18 and 1.62, respectively, and the difference was statistically significant (p < 0.05). Besides, few iron nanoparticles were deposited in the tumor tissue in the targeted group . The Fe levels in the tumor tissue in the SPIO-aPD-L1-Cy5.5 group were significantly higher than in the SPIO-IgG-Cy5.5 group (p < 0.05).The distribution of Fe in tissues was validated by ICP-MS. The liver and spleen had the greatest accumulation of Fe ; howeverIn 4T1-bearing nude mice that received SPIO-aPD-L1-Cy5.5, NIRF signals were detected in the whole body. Besides, strong NIRF signals were observed in the tumor region in the targeted group at 6 h , in contin vivo.Moreover, H&E staining of SPIO-aPD-L1-Cy5.5 NPs showed normal pathological morphology and no histopathological damage response in tissue sections of all organs, compared with the nontargeted group . The cytIt has been established that PD-L1 is upregulated in TNBC, and its expression is negatively associated with poor patient prognosis and correlates with ICI treatment response rate. Therefore, an accurate means of monitoring PD-L1 expression at the tumor site can prevent PD-1/PD-L1 responders from discontinuing immunotherapy due to erroneous PD-L1 results , 29. How∗ value. In the present study, the NPs SPIO-aPD-L1-Cy5.5 synthesized was found to have a T2 relaxation rate of 199.48 s−1 mM−1; importantly, this complex exhibited excellent MR imaging properties in vivo.MRI is a well-established method in breast imaging, with various clinical applications, including the noninvasive differentiation between benign and malignant breast lesions, treatment effect evaluation, and the evaluation of high-risk patients. Commonly used contrast agents are broadly divided into T1-positive and T2-negative contrast agents. SPIO is widely acknowledged as a superparamagnetic material that provides a rapid reduction in the intensity of the T2 signal. Liu et al.  employedThe surface chemistry and size of SPIO nanoparticles can influence their biodistribution pattern and circulation time in the body. The biodistribution patterns of SPIO nanoparticles have been mostly characterized in the liver and spleen , 31. Stu∗ value at the tumor site, especially the targeted nanoparticles. The nanoparticles prepared by our group reached the tumor site via its enhanced permeation and retention (EPR) effects [The nanoprobe prepared by our group exhibited a relatively uniform and appropriate size. Furthermore, we demonstrated the biocompatibility and molecular imaging of NPs. The study showed that both targeted and nontargeted nanoparticles could effectively reduce the T2 effects , 37. The effects . Active  effects , 40. TheIn the present study, the T2-negative contrast agent SPIO exhibited more sensitive signal changes than the Gd agent while avoiding the nephrotoxicity associated with the latter. Moreover, the synthesized NPs allow effective, noninvasive, and real-time detection of the expression of PD-L1 in the tumor tissue. However, the relationship between the PD-L1 expression and changes in the MR signals was not quantified, warranting further studies.in vivo and H&E staining. This work provides the basis for future studies on molecular imaging of PD-L1 in cancer patients.In conclusion, our group designed a dual-modality PD-L1-targeted nanoparticle probe, which exhibited slight cytotoxicity and could specifically bind to the cell surface. Furthermore, we validated its biocompatibility and targeted ability by NIRF/MR imaging


M = 9.09, SD = 0.80). The measures were based on the subjective appraisals of the sessions made by the participating children, including quantitative and qualitative assessments of the degree of satisfaction of the participants. The results showed that there were similar levels of satisfaction with the sessions that did or did not use serious games as a complement to the program. However, only satisfaction with the sessions that used serious games (and not satisfaction with the sessions that did not use them) contributed significantly to explaining both the enjoyment of the activities and the interest in the subjects. Satisfaction with serious games was significantly and positively associated with fun, easiness, ability to understand the session, and ability to cope with emotions. Qualitative analysis showed three main themes, namely: positive aspects, negative aspects, and opportunities for improvement of the program. Overall, these results indicate that children’s satisfaction with the ‘Me and Us of Emotions’ program is related to serious games, suggesting the relevance of using this complementary tool more often when intervening with younger generations.The use of serious games may be an appealing and complementary way to motivate curriculum-based social and emotional learning (SEL); still, investigation into this potential usefulness is scarce. This study aims to address the usefulness of serious games within the program ‘Me and Us of Emotions’. Specifically, we analyzed the differences in children’s satisfaction in sessions that did or did not use serious games as a complement to the intervention, explored the contribution of using serious games to the global satisfaction with the program, and explored children’s qualitative feedback regarding the sessions. The participants were 232 children (122 boys and 110 girls) aged between 8 and 12 years old ( The empirical literature has consistently established the importance of universal and preventive approaches to promoting social and emotional skills in children within school contexts ,2,3,4. PSEL also encourages prosociality and compassionate motives ,12. AccoThe majority of SEL programs have been traditionally taught within the curriculum ,4. In reOne way to measure the usefulness of serious games relies on assessing participant engagement, for example, the extent to which participants are sufficiently attracted to and involved in the program , which cDespite the relevance of knowing about participants’ engagement with the interventions to better interpret the outcomes and continuously improve the interventions, it is a rare practice in the SEL literature ,33. It bM = 9.09, SD = 0.80) of whom 52.6% (n = 122) were boys and 47.4% (n = 110) were girls. There were gender differences for age, t(230) = 2.74, p = 0.007, Cohen’s d = 0.360, with boys being significantly older than girls . Regarding school year, 44.8% (n = 104) were in the 3rd grade and 55.2% (n = 128) were in the 4th grade. Boys and girls were evenly distributed by school year, X2(1) = 0.952, p = 0.329.Participants were 232 children aged 8–12 years old  or a control group (CG). In the present study, only the data from the EG was used; participants in this group received the ‘Me and the Us of Emotions’ program.The Me and the Us of Emotions program  compriseSatisfaction with the program was assessed weekly after each session by each participating child. Children answered the question “How much did you like this session?” using a 5-point Likert response scale ranging from “I didn’t like it at all” to “I liked it a lot”. The total satisfaction scores by type of session were computed by summing answers provided to this item across sessions 2, 7, 8, 9, and 10  and across sessions 1, 3, 4, 5, and 6 .After sessions 9 and 10, both using serious games, participating children answered 4 questions: fun with serious games (“How often did you have fun playing this game?”); easiness (“How easy was it to understand how to play?”); usefulness in relation to understanding the session (“Did the game help you to understand the session?”); and usefulness in relation to understanding how to cope with emotion . All these questions were rated on a 5-point scale ranging from 1 “None” to 5 “Much”.This questionnaire included five items and was completed at the end of the program. The first item was “You think that the sessions were…” rated on a 5-point scale ranging from “Not good at all” to “Very good”. The other four items were “How would you rate the sessions?”; “Did you like the activities conducted during the session?”; “What is your interest in the subjects we talked about?”; “Did you like the music?”; and “Did you like the games?”, which were rated on a 5-point Likert scale ranging from “None” to “Very much”. In addition, four open-ended questions were included to be analyzed thematically .t-tests [t-test was also used to compare the satisfaction between the sessions that did and did not use serious games. Pearson product–moment correlations were performed to explore the relationships between the variables in the study [Statistical analyses were conducted using PASW Software . Descriptive statistics were computed to explore the demographic variables and gender differences were tested using independent sample t-tests . Additiohe study ,40. Multn = 59, M = 4.77, SD = 0.48 vs. M = 4.72, SD = 0.46, respectively), t(58) = 1.062, p = 0.292.The results showed no differences in satisfaction between the sessions that did and did not use serious games  = 1.132, p = 0.330, liking the music, F  = 0.498, p = 0.611, and liking the games, F  = 0.970, p = 0.385.No significant effects of satisfaction with the sessions that did and did not use serious games were found in enjoying the sessions, F  = 19.416, p < 0.001, accounting for 39.7% of that enjoyment. Only satisfaction with the sessions that used serious games was a significant predictor. The same predictive model was significant for the interest in the subjects being covered in the session, F  = 15.325, p < 0.001, with satisfaction with the sessions that did and did not use serious games accounting for 33.8% of the variance of that interest. Again, only satisfaction with the sessions that used serious games emerged as a significant predictor , easiness , ability to understand the session , and ability to cope with emotions .Satisfaction with the use of serious games (in sessions 9 and 10) was significantly and positively associated with fun  positive aspects, (b) negative aspects, and (c) opportunities for improvement to the program. In each major theme, participants’ responses were grouped into several sub-themes that best reflected participants’ verbalizations .Regarding the theme “positive aspects”, three sub-themes emerged, namely, learning emotion regulation strategies, experiencing positive emotions , and gaining knowledge about emotions . The theme “negative aspects” included a reduced opportunity for playing serious games and experiencing difficult emotions. Finally, the “opportunities for improvement” were the following: providing for less noise during the sessions and better behavior on the part of the participating children, addressing more emotions, using more serious games, and increasing the duration of the sessions.The value of universal social–emotional learning-based programs for children in school contexts is well-known ,3,4,7 buThe results showed that children reported similar levels of satisfaction with the sessions that did and did not use serious games as a complement to the program and that those diverse sessions did not differently impact on the enjoyment of the sessions, liking the music, and the liking games. The acceptability and the efficacy of traditional SEL programs have been previously proven ,6 as hasAlternatively, only satisfaction with the sessions that used serious games contributed to explaining both the enjoyment with the activities and the interest in the subjects; satisfaction with the sessions that did not use those games was not a significant contributor to that enjoyment and interest. So, although the children were similarly satisfied with all the sessions, using serious games helped them enjoy the activities more and be more interested in the sessions’ themes. Complementing sessions with serious games seemed to provide an appealing, interactive, and motivating environment, which aligns with previous literature that demonstrated that this complementary use of serious games could be a way of enhancing engagement and motivation in children .In the current study, the two final sessions that used serious games were assessed by children regarding their fun, easiness, usefulness to understand the session, and usefulness in managing the emotion. The results suggest that children who were more satisfied with serious games tended to experience more fun and more easiness and found the games more useful for understanding the session and managing emotions. Although the limitations linked to the correlational nature of these findings, they provide some indication that when serious games are included in face-to-face social–emotional skills-based programs, they can facilitate children’s acquisition of knowledge and skills, which is consistent with the results from the few existent studies ,27. AlsoThe qualitative study also highlighted the importance of serious games as a complementary tool to the programs. The “negative aspects” highlighted by children were the reduced opportunity for playing serious games and experiencing difficult emotions. In addition, the “opportunities for improvement” included suggestions not only for ameliorating climate and behavioral manifestations during the sessions , but also for increasing the session duration, targeting more emotions, and using more serious games. It seems that both individual and program factors were highlighted by children both as positive and negative aspects and, consequently, as aspects that could be further improved. Similarly, participant factors have been emphasized in other studies, such as attitudes toward learning and motivation, as well as program factors, such as length ,35.Some limitations of the present study should be considered. The first limitation is related to the sample size. Although the current sample is considered large, not all participants consistently reported their satisfaction after each session . In addition, the access to serious games was not equal for all children in the session due to time constraints. Although online access to serious games was possible through the ‘Me and the Us of Emotions’ program online platform, some children may not have had a sufficient internet connection at home. A further limitation was that the specific aspects concerning the fun, easiness, and usability of the serious games assessed in sessions 9 and 10 were not evaluated in the other sessions that used games; so, the findings may be specific to the games used in those sessions (and the cumulative effect of the intervention) and not to the use of serious games in general. Future studies should consider the same measurement methods over time. The control group was on a waiting list and not active, which limited the possible comparison of the complementary aspect of serious games between the groups. Future studies should also address the impact of serious games on participants’ emotional development. The current findings should be seen as a preliminary assessment of the potential usefulness of serious games as a complementary tool for social–emotional learning programs, and a larger study informed by these results is ongoing.Both political and educational audiences have come to realize that a child’s social and emotional well-being are important and can be fostered in school contexts through SEL programs. The present paper analyzed children’s perceptions of using serious games as a complement to the social–emotional activities of the ‘Me and the Us of Emotions’ program. Our quantitative and qualitative findings converge to suggest the usefulness of adding serious games as a complement to a social–-emotional skills-based program, as they contribute to enhancing children’s satisfaction. Given the importance of SEL programs and the benefits they have been found to provide ,4,7, it


Land use change has long-term effects on the structure of soil microbial communities, but the specific community assembly processes underlying these effects have not been identified. To investigate effects of historical land use on microbial community assembly, we sampled soils from several currently forested watersheds representing different historical land management regimes . We characterized bacterial and fungal communities using amplicon sequencing and used a null model approach to quantify the relative importance of selection, dispersal, and drift processes on bacterial and fungal community assembly. We found that bacterial communities were structured by both selection and neutral  processes, while fungal communities were structured primarily by neutral processes. For both bacterial and fungal communities, selection was more important in historically disturbed soils compared with adjacent undisturbed sites, while dispersal processes were more important in undisturbed soils. Variation partitioning identified the drivers of selection to be changes in vegetation communities and soil properties  that occur following forest disturbance. Overall, this study casts new light on the effects of historical land use on soil microbial communities by identifying specific environmental factors that drive changes in community assembly. Soil microbial communities play key roles in terrestrial ecosystems, facilitating essentially all ecosystem processes . HoweverIn addition to effects of present land use, currently unmanaged ecosystems with different historical management regimes may also host distinct microbial communities . For exaTo investigate microbial community assembly across historical land uses, we sampled soils from eight forested watersheds at the Coweeta Hydrologic Lab in North Carolina, USA. Four of the watersheds were disturbed ~4–8 decades previously by management activities including clear-cutting, cable-logging, conversion to pine monoculture, and pasture conversion Table . AdjacenBray) then distinguishes between specific neutral processes, where compositional turnover less than or greater than null expectations indicates homogenizing dispersal or dispersal limitation + drift, respectively. Turnover not differing from null indicates drift alone. We determined differences between bacterial and fungal βNTI distributions using a Kruskal–Wallis test and determined effects of historical disturbance on the proportions of specific processes using Z-tests. We investigated potential drivers of selection  by conducting variation partitioning on βNTI matrices, similar to the approach of Fillinger et al L. tulipies Table  suggestsDispersal processes were more important in structuring bacterial and fungal communities in reference soils than in disturbed soils Fig. . GreaterOverall, our results reveal clear legacies of historical land use on soil microbial community assembly; contrary to what has been shown for recently disturbed systems, microbial communities in historically disturbed sites can be more strongly shaped by selection than their undisturbed counterparts. However, it is possible that these patterns are specific to our soils within temperate forests of the eastern US, which should be assessed by future work. Regardless, the differences in community assembly we report are likely to influence ecosystem recovery following forest disturbance. For example, ecosystem processes associated with specific fungal taxa may recover slowly or not at all following forest disturbance, as these taxa will not be quickly recruited from undisturbed sites via dispersal Fig. . In geneSupplementary information


A very attractive advantage of graphene is that its Fermi level can be regulated by electrostatic bias doping. It is of great significance to investigate and control the spatial location of graphene emission for graphene thermal emitters, in addition to tuning the emission intensity and emission spectrum. Here, we present a detailed theoretical model to describe the graphene emission characteristics versus gate voltages. The experimentally observed movement of the emission spot and temperature distribution of graphene emitters are basically in agreement with those from the theoretical model. Our results provide a simple method to predict the behavior of graphene emitters that is beneficial for achieving the spatial dynamic regulation of graphene infrared emission arrays. As a high-profile two-dimensional material, graphene has attracted extensive interest in worldwide for its excellent electrical, thermal, and optical properties ,2,3,4. IIn recent years, graphene thermal emission due to Joule heating has attracted a great deal of attention, and many studies have focused on enhancing the emission intensity or tuning the emission spectrum of heated graphene ,9,10,11.In this work, we start with the charge conservation and tunability of carrier density and present a detailed theoretical model to calculate the distribution of the voltage, carrier density, locally generated heating power, and temperature along graphene. We find that this model can provide a clear and simple picture of the device behavior, in agreement with the results from simulations and experiments. For example, the calculated positions of minimized carrier density are consistent with those extracted from graphene infrared emission images. Under low gate voltages, maximum temperatures in the experiments are lower than those calculated by the temperature equation, but measured temperatures under high gate voltages are similar to those calculated by the equation. Moreover, the occurrence of another hot spot could be explained by simply introducing a locally trapped charges function into the carrier density equation. These results are helpful for realizing the controllable spatial emission of graphene emitters in the future.x is the direction along graphene (from drain to source), V(x) is the electrostatic potential, e is the electron charge, and w is the width of graphene. According to the charge conservation, the current is constant everywhere along graphene, so the carrier density depends on the electrostatic potential distribution, which could be written as [The theoretical model is based on the assumption that the carrier density of graphene is minimized when the Fermi level crosses the Dirac point, where the conduction band and valence band touch each other. For graphene thermal emitters on a itten as (2)V(x)=Here, we ignore the recombination length of electrons and holes in graphene, so carriers are either electrons or holes but cannot be both. Therefore, the point that separates electron and hole regions has the lowest charge density, resulting in the highest resistance. According to charge conservation in the steady state and Joule heating, the current is equal everywhere and heating is proportional to the resistance, so the hottest place would occur at the point separating electron and hole regions. Meanwhile, according to Equation , only insgn(x) is sign function, Combining Equations (1) and (2) with boundary conditions, we can obtain the electrostatic potential expression along graphene and the position expression with minimum carrier density.The expressions for current, local carrier density, and Fermi level can also be derived as follows:Because the infrared emission intensity is related to the local Joule heating of graphene, and considering the presence of the carrier density . In the simulation, different kinds of carrier density in graphene are taken into account with the following equations: ,15.(10)The hot spot location, maximum temperature, and current calculated from equations and simulations are compared in A graphene flake was mechanically exfoliated on a p-doped A constant drain voltage of 70 V was applied to the graphene thermal emitter, while recording the spatial locations of graphene infrared emission as a function of applied gate voltages by an infrared CCD. All measurements were performed in vacuum to avoid the oxidation of graphene, and the emission intensity at each gate voltage in Through correcting the infrared CCD with a blackbody 590 K–740 K), temperatures of hot spots in 0 K–740 Kubstrate ,17, as tInterestingly, we found that a stationary light spot appeared at a place about 20 graphene . In viewThe relationship between temperature and gate voltage is calculated using Equations (8), (9) and (11) and plotted in In summary, we theoretically and experimentally investigated the spatial location of thermal emission in gate-controlled long channel graphene devices. The observed movement of the emission spot and temperature distribution are consistent with those obtained by the theoretical model, confirming that controlling the gate voltage is an effective method to tune the emission location and emission intensity. In addition, the relationship between the carrier density and Fermi level could be deduced by the theoretical model, which is helpful to understand the internal mechanism of graphene emission.


We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0–100% for making two-dimensional graphene–Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values.We report the synthesis and characterization of graphene functionalized with iron (Fe 3O4–graphene (FG) nanohybrids and magnetothermal measurements of FxGx100–  nanohybrids (25 mg each) at a 633 kHz alternating magnetic field of strength 9.1 mT.Synthesis of Fe According to the factsheet of February 2018 issued by the world health organization (WHO), cancer is the cause of almost 8.8 million deaths annually.3 It is imperative to develop an effective and accurate treatment method for this malignant disease. The typical therapies in-practice for cancer treatment include radiation therapy, chemotherapy, and surgery. However, apart from being painful, these therapies lead to several side effects such as damage to healthy tissues, fatigue, alopecia and multidrug resistance (MDR). Magnetic hyperthermia (HT) is an alternative and promising non-invasive approach for cancer treatment, where magnetic thermoseeds are injected directly into the tumor area of the patient.4 The cancerous area, containing the implanted thermoseeds, is heated to an elevated temperature through magnetic nanoparticles (MNPs). The heating phenomena is mainly induced in the magnetic nanoparticles under alternating magnetic field due to hysteresis, Néel and Brownian relaxation losses. Brown relaxation losses occurs when the nanoparticle rotate in the fluid and produce heat via a fraction mechanism in the aqueous medium. As there is a reduced blood flow in the tumor area, containing disorganized blood vessels, the heat dissipation to the surrounding area is limited. Therefore, cancerous cells are more susceptible for apoptosis at relatively mild heating up to ∼42 °C as compared to healthy cells. It has been reported that a temperature range of 41.8–44 °C provides the most suitable conditions for entire body hyperthermia.5 This is due to the leaky vasculature of the cancer cells that obstructs dissipation of thermal energy from them, as compared to the well-ordered blood vessels and nerves connected to healthy cells that can stand against heat by a more efficient heat dissipation, and a greater excretion of the heat shock proteins.6,7 The unique feature of nanoparticles to act selectively on the tumor cells sparing the healthy cells makes this therapeutic technique much more accurate as compared to the conventional methods.8,9Cancer treatment with high accuracy is a major concern of the medical community. For instance, hyperthermia or heat mediated therapy has today become of great significance utilizing energy absorbing nanoparticles.3O4 remained a hot contestant in hyperthermia applications due to their biocompatibility, strong intrinsic magnetic properties and their use in bio-medical applications. The use of these materials in magnetic resonance imaging (MRI) contrast enhancement, magnetic hyperthermia cancer therapy, and targeted drug delivery is a manifestation of their biocompatibility.10–15 However, the bare pristine Fe3O4 nanoparticles possess strong anisotropic dipolar interactions and high magnetization that result in agglomeration and precipitation. Due to these factors, their colloidal solubility is lost, and their activity is reduced. Therefore, it is challenging to incorporate Fe3O4 nanoparticles in both in vitro and in vivo experiments. To prevent their agglomeration and precipitation, we have developed a support of reduced graphene oxide sheets, for making Fe3O4 nanoparticles immobilized.Ferrites such as Fe2 bonded carbon atoms. The introduction of the exfoliation technique in 2006 for producing single-layer graphene,16 has gained tremendous attention from application perspective. Large thermal conductivity (κ ∼ 5.3 × 103 W m−1),17,18 high flexibility and strength ,18–20 and excellent biocompatibility of graphene lead to remarkable properties for the development of prototype devices for biological applications such as miniaturized single fat-cell glucose sensors,21 graphene-based single-bacterium bio-device, label-free DNA sensor, and bacterial DNA/protein.22 Controlled tunability of the fabrication and functionalization of graphene is required, to achieve a remarkable performance from graphene-based devices, making it an important topic of contemporary research.Graphene is a single-atomic-thin planar sheet of sp23–25 Among all, Hummer's method is the most famous and reliable for economical large-scale production of graphene. The Graphene Oxide (GO) obtained by Hummer's method is hydrophilic owing to numerous attached functional groups , making the graphene easy to functionalize with other species. Cong et al. reported the synthesis of hydrazine reduced GO sheets (prepared by modified Hummer's method), that were post decorated with Fe3O4 nanoparticles. These Fe3O4 functionalized graphene sheets could be used as a magnetic resonance contrast. Jing Su et al.27 prepared graphene–Fe3O4 nanohybrids via a hydrothermal approach. These materials exhibit superparamagnetic properties for biocompatible controlled drug delivery.Thus far different techniques have been developed to produce graphene stacks of varying thicknesses, a post-functionalization to make hybrids of graphene with other materials. Morphologies and properties of free standing nano-islands of graphene in layered hybrid systems have been found to be closely related to their growth strategies.3O4–graphene nanohybrids. The synthesized nanohybrid materials are applied to investigate magnetic hyperthermia and their functionality is compared with that of pristine Fe3O4 and reduced graphene oxide. Large specific heat capacity of graphene and the charge transfer effect between graphene sheets and immobilized magnetic Fe3O4 nanoparticles enhanced the magnetic hyperthermia effect. The best thermoseed agent was determined by calculating the specific absorption rate (SAR).Although Hummer's method provides an efficient approach for the introduction of new species to a 2D graphene oxide system in the form of hybrids however, reduction of GO is an important stage for a reliable functionalization of defect free graphene. In this work, we adopted thermal reduction method for producing graphene and FeArtificial intelligence (AI) has been dominant in health care and medical sciences since the advent of current century. Researchers and futurists have concluded that the collaboration of this technology with the doctors can make wonders and that there is still a long way for scientists to go to unveil the extraordinary potential of AI to transform health care into a much more modern and efficient medical care system. Keeping this in view, we have also utilized AI to produce improved nanoparticles for hyperthermia treatment.i.e., AI. Deep learning consists of artificial neural networks (ANN) based algorithms. ANNs have been used by scientists to analyse time series data for prediction and forecasting.28,29We have used a deep learning algorithm for the time series modeling of hyperthermia data. Deep learning is a subset of machine learning which is a subfield of a bigger domain We have developed a system of six artificial neural networks to assess the best nanoparticle. ANNs with exogenous input have this capability to extract information from the past values in the data and process it to learn and then predict step ahead values which gives us an insight of the performance of each particle. However, the algorithm requires as much data as possible for improved predictions.2.3O4–graphene nanohybrids, high quality expandable graphite powder of mean size 25 μm was purchased from Aldrich (purity 99.99%), FeCl3·6H2O from Riedel-de Haen (purity 99%), FeCl2·4H2O (purity 99.8%) and HCl from Merck, KMnO4 from BDH (purity 99%), 32% NH3 solution and high grade H2SO4 and H2O2 (30 wt%) were purchased from Panreac. All reactions were carried out using deionized (DI) water.For synthesis of Fe2.1.30 5 g graphite powder was added in 125 mL H2SO4 (99.99% assay) in a flat-bottomed flask at 0 °C followed by vigorous stirring to avoid agglomeration. Once the powder was well dispersed, 15 g KMnO4 was added to the mixture slowly, at a low temperature, below 15 °C. Gradually the mixture was brought to room temperature. After the reaction, mixture became pasty and turned light brown in color. 150 mL of DI water was added slowly to the mixture to dilute it, after which 17 mL H2O2 (30 wt%) was added, that changed the mixture color to yellow. Finally, the mixture was washed with 1 : 10 HCl (1 M) solution to remove residual ions. Grey colored GO powder was obtained after drying the solution in oil bath with continuous stirring (10 rpm) for 8 hours at room temperature (25 °C).GO was synthesized using graphite powder as a starting material by modified Hummer's method.2.2.xGx100– compositions have been synthesized, where x  refers to the weight percentage of magnetite in the nanohybrid. Note the composition with x = 0 specifies pure graphene and x = 100 specifies pure magnetite. Specific amounts of FeCl3·6H2O and FeCl2·4H2O and graphene oxide (GO) were weighed for each composition. Stoichiometric quantities of FeCl3·6H2O and FeCl2·4H2O were dissolved in 25 mL de-ionized (DI) water to obtain their 0.04 and 0.02 molar aqueous solutions, respectively. The required amount of GO was dispersed in DI water (250 mL H2O for 0.9 g GO) for each composition. In order to transform the attached carboxylic acid groups to carboxylate anions, the dispersion was sonicated for 1 h. Then, 0.02 mole of FeCl2·4H2O and 0.04 mol of FeCl3·6H2O were dissolved in DI water and added dropwise to the GO solution at room temperature with vigorous stirring. On completion of ion exchange reaction, 32% NH3 solution was added drop by drop until the pH of solution became 10 that is required for the formation of Fe3O4 NPs.31 All the compositions were dried in oil bath with continuous stirring (10 rpm) for 8 hours at room temperature (25 °C).Magnetite–graphene oxide F2.3.3O4–GO compositions in dried powder forms were thermally reduced in a quartz tube furnace for 1 h at 800 °C (heating rate 10 °C min−1) at 300 cm3 flow rate of forming gas . The samples were named according to the weight % ratio in the compositional formula FxGx100–  as G, F25G75, F45G55, F65G35, F75G25, F85G15 and F, respectively. For example, F45G55 refers to the nanohybrid containing 45 wt% magnetite and 55 wt% graphene. Schematic diagram for synthesis of FG nanohybrids is shown in For the fabrication magnetite–graphene (FG) nanohybrids, Fe2.4.31 method. Fe3O4 NPs were obtained on reacting iron-II (Fe2+) and iron-III (Fe3+) ions in an ammonia solution (pH 10) in the molar ratio 1 : 2 respectively, at room temperature by stirring the solution for 30 min at 4000 rpm, following the reaction in eqn (1)Magnetite nanoparticles were prepared by co-precipitationThe solution was washed several times at room temperature by stirring the dispersion for 30 min at 3000 rpm, to remove the unwanted ions and until it attained a pH of 7. Magnetite nanoparticles were centrifuged from the solution and dried at room temperature.3.15,32,33 Furthermore, several models based on nonlinear autoregressive structure have been proposed.34–36 We have developed a neural net time-series model using Neural Net Time Series app on MATLAB R2018b. It takes one or more time series for prediction; however, our time-series difficulty is to make a prediction by utilizing the l past values of a time series which is being predicted (y(t)), and another time-series (x(t)), in our case the 100% magnetite particle. In this basis, we have used Nonlinear Autoregressive with External Input (NARX) neural network. NARX is a recurrent network capable to model dynamic systems,2 it is not only able to predict output value which is regressed on the previous values but is also used for nonlinear filtering  = 37 However, our choice of Bayesian regularization is influenced by the involvement of Bayesian theorem which incorporates prior data along with maximum likelihood function to give posterior distribution.38Data is fed into the three layered  network consisting of 10 hidden neurons and two-time delays . Size of39 Adopting a probabilistic approach towards machine learning is the most reliable strategy to solve a problem like future prediction which is based on uncertainty.40 It may take a little longer but yields finer results and has emerged to be the most robust and vigorous one in comparison to the standard back propagation NNs. Regularization itself is meant to overcome the overfitting issue, hence the models trained using BR are difficult to overtrain and overfit.41 It utilizes posterior probability which involves utilization of Bayesian theorem for parametric optimization and updating the knowledge from prior to posterior.42 Bayesian inference is a highly commendable approach for statistical analysis of stochastic processes.43BR happens to be a better choice for quantitative researches, due to its potential to unveil complex data patterns and interrelations.The training process continues till the optimal result is achieved and is terminated as the generalization stops improving, the model can be trained for the maximum number of 1000 epochs.To are the observed values and Te are the estimated ones. Moreover, regression (R) values have been calculated to see the correlation between output and target. Values of R close to 1 are considered to be optimal, it indicates close relationship between output and target.After training, the assessment of the accuracy of the predicted results is carried out on the basis of Mean Squared Error (MSE) 4.i.e., 65.6 μm for sample G. It is evidenced that for low Fe3O4 samples (up to 45%), Fe3O4 nanoparticles are evenly distributed within the graphene matrix with a very little degree of agglomeration. However, with increasing the content of Fe3O4, further agglomeration is observed. It can be concluded that, the average size of Fe3O4 nanoparticles significantly varies with the content of Fe3O4 with nano scale length. The image in 3O4 nanoparticles with non-uniform size distribution due to magnetic anisotropic interactions.JEOL (Japan) JSM-6400F field emission scanning electron microscopy (FE-SEM) equipped with electron diffraction microscopy (EDX) was used for morphological and elemental analysis of Functionalized Graphene (FG) nanohybrids as presented in 3O4 on the graphene surface sample F75G25 was randomly selected for energy dispersive X-ray spectroscopy (EDX) as shown in 3O4 nanoparticles are distributed between the layers of the graphene sheets, which lead to the formation of Fe3O4–graphene nanohybrids.To confirm the presence of the Fe3O4 and FG samples were exposed to DC magnetic field, up to 20 kOe, in Lake Shore 7404 (US) vibrating sample magnetometer (VSM), at room temperature. The field dependent M(H) curves of all the samples (3O4) for a comparative study of their magnetic properties. The inset shows the M(H) loop of pure graphene. Remanence (Mr) and coercivity (Hc) values for all samples are shown in Pristine graphene, Fe samples  were norMr) and coercivity (Hc) values of samples are not increasing monotonically with the Fe3O4 content. As seen in SEM images 3O4 content, further agglomeration is observed. It can be seen from combined analysis of SEM and VSM results that Hc and Mr values are mainly dependent on degree of agglomeration of Fe3O4 rather than its concentration. Moreover, the magnetic behavior of a magnetic component dispersed in a nonmagnetic reduced graphene oxide matrix depends not only on the quantity of the magnetic component but also on how it is dispersed within the matrix.44 The weak magnetization of graphene is due to the presence of local defect states and non-magnetic nature.45 Sample G attains a maximum saturation magnetization of 0.08 emu g−1. The measured saturation magnetization (MS) of pure Fe3O4 (sample-F) ∼42 emu g−1 is much lower than the value reported for bulk counterpart (85–95 emu g−1). This is due to the well-understood size dependence of magnetization in nanoparticles in which surface spin disorder can lead to a magnetically dead surface layer.46 In case of FG samples, the magnetic behavior  is not depending upon the magnetic component. For example, remanence and saturation magnetization of the F45G55 sample is comparable to that of F75G25i.e., ∼6 emu g−1 and 20 emu g−1 respectively. This can be due to the intercalation-dependent magnetic interactions. As shown in the SEM images  was measured using NAN201003 MagneTherm (UK) induction heating unit for 25 mg of each sample powder exposed to a 633 kHz alternating magnetic field of strength 9.1 mT. A significant heating upshot was observed in all the synthesized nanohybrids  of each nanohybrid sample was determined by weight % contribution of Fe3O4 and graphene in the given composition. Specific heat capacity of Fe3O4 was taken as 0.937 J g−1 K−1 (ref. −1 K−1.17Specific absorption rate (SAR) is the rate at which MNPs convert magnetic energy into heat. SAR is considered as a figure of merit in hyperthermia measurements. The specific absorption rate (SAR) of the samples have been calculated from the heating curves, using the following K−1 ref.  and thatvs. magnetite content w.r.t wt% ratio in different FG nanohybrids. SAR value obtained for pure magnetite sample (F) is smaller than that reported by P. Burnham et al. i.e.∼5.813 W g−1 for dry magnetite.50 This difference is possibly due to the magnetic field strength (200 Oe), alternating frequency (282 kHz) and particle size (particle size = 15.3 nm) difference. Interestingly, the SAR value of F45G55 sample is ∼1.5 times larger and appx. same for F25G75 samples, as compared to that of the pure magnetite (F). Such an intriguing feature must be due to the large area matrix provided by the reduced graphene oxide sheets, and its heat capacity which is higher than that of pure magnetite. In details, the heat capacity of graphene is about twice that of magnetite, leading to higher SAR for lower content of Fe3O4. Additionally, the highest SAR obtained for sample F45G55i.e., 6.45 W g−1, is due to an excellent exfoliation of graphene and most uniform intercalation of magnetite nanoparticles, as has been observed in SEM images. These behaviors also led to reduced frustration of moments for highest saturation magnetization  values have been calculated to see the correlation between output and target. Calculated values for all the compounds are given in the following Six NARX models are obtained, one for each of the components in R values for the six composites. These values were obtained after completing the testing phase of the model. The model trained for the assessment of F45G55 performance in comparison to pure magnetite yielded highest MSE value. It turns out to be the most different one. Moreover, the R values depict the accuracy of the results obtained from the model which is also high for this composition. The plots obtained from the trained network for F45G55 are as following:i × target + j; where i is slope and j is the y-intercept. Here, we have three plots for different values of j. Each of them shows a meaningful correlation between target and output since the value of R is very close to 1, which is the ideal case. We have achieved maximum regression values for all the particles. x-axis and the predicted versus observed values on the y-axis. The other smaller graph in i.e., the predicted results. Our training and test outputs lie on the response line. Hence, the error is obtained by comparing the values from the response line to the ones that lie above or below the line. So, if the target value lies above the line, we obtain a positive error and, negative otherwise.The regression/scatter plots on y-axis and errors on the x-axis. The maximum number of instances do not have zero error. This shows the predicted results are not very close to the target values, time series and performance plots further validate this interpretation. versus epoch count. As stated earlier, MSE is the difference between the observed and the simulated, therefore it should be lower. According to our motivation, the particle that obtained the highest error is the most favorite one, and for F45G55, MSE obtained in the training phase is 0.44703, where the model achieved optimal results after 71 epochs. However, it is seen that Bayesian regularization does not require validation, this is due to this fact that the sole purpose to perform validation check is to make sure either error increases or decreases while training and avoid overfitting in the testing phase, making Bayesian method encounters successfully while training the model. Most importantly, our experimental results also have shown that highest SAR value is obtained for sample F45G55  were fabricated. All the compositions were characterized and analyzed morphologically and magnetically at microscopic level. Hyperthermia measurements showed a high specific absorption rate (SAR). Sample containing 45% magnetite and 55% graphene i.e., F45G55 is found to have the largest SAR value of 6.45 W g−1 with saturation magnetization ∼20 emu g−1, that is ∼1.5 times greater than that of pure magnetite (4.32 W g−1) with saturation magnetization ∼42 emu g−1. The role of graphene is to reduce frustration of magnetic moments by monitoring the dipolar interactions with better exfoliation and low agglomeration of Fe3O4 nanoparticles. Moreover, large value of specific heat capacity of graphene contributes an increase in SAR of nanohybrids to even 1.5 times larger than that of the pure magnetite. Nonlinear Autoregressive with External Input (NARX) models are obtained for each of the nanohybrid composition. The accuracy of the predicted results has been evaluated on the basis of Mean Squared Error (MSE). The highest MSE value was obtained for the composition containing 45% magnetite and 55% graphene (F45G55) nanohybrid in the training phase i.e., 0.44703 which is where the model achieved optimal results after 71 epochs. Hence, F45G55 sample was found the best nanohybrid with highest SAR and MSE values for hyperthermia applications in low dosage. With suitable surface functionalization, biocompatible Fe3O4-graphene nanohybrids can be useful candidates for localized magnetic hyperthermia applications.The goal of this work was to develop biocompatible two dimensional (2D) magnetic system of high thermal conductivity for the treatment of malignant tumors The authors report no conflicts of interest.


Capsicum cultivar samples. The chemical, structural, and morphological propertiesof the graphene-type materials were evaluated. The materials exhibitedgood adsorption capability of matrix interferents without compromisingthe extraction efficiency of target analytes when compared with othercleanups using commercial sorbents. Under optimal conditions, excellentrecoveries were obtained, ranging from 90 to 108% with relative standarddeviations of <14%. The developed method showed good linearitywith a correlation coefficient above 0.9927, and the limits of quantificationwere in the range of 0.35–0.82 μg/kg. The developed QuEChERSprocedure using reduced graphite oxide (rGO) combined with GC/MS wassuccessfully applied in 20 samples, and the pentabromotoluene residueswere quantified in two samples.A new applicationof graphene-type materials as an alternativecleanup sorbent in a quick, easy, cheap, effective, rugged, and safe(QuEChERS) procedure combined with GC–ECD/GC–MS/GC–MS/MSdetection was successfully used for the simultaneous analysis of 12brominated flame retardants in  Although the use of certain BFRs was banned and restrictedby the European Union due to their persistence and bioaccumulationin the environment, they were detected in biota, food, and feed samples.7Although BFR levels found in food samples are mostly associatedwith environmental contamination, the potential influence from packagingcannot be excluded. A wide range of plastic products may contain BFRs.Material recycling may potentially reintroduce the BFR into new plasticproduct cycles and lead to increased exposure levels, for example,through the use of plastic packaging materials.14 The toxicity of these plastic additives to humans demonstrated thatBFRs have the potential to adversely affect endocrine functions andthe central nervous and reproductive systems. The different brominateddiphenyl ethers (BDE) appear to have a similar toxicological profile,with the liver, kidney, and thyroid as the main target organs.15 Several analytical techniques are used in monitoringstudies of pesticides and other contaminants in food samples.18 These include mainly liquid chromatography and gas chromatographyfor multiple contaminant analysis and electrochemical techniques usuallyfor one target.20Consumption of BFR-contaminated food products may result in serioushealth problems in human beings.Capsicum cultivars are samples that have a complexcomposition since they contain numerous chemicals including steam-volatileoils, fatty oils, capsaicinoids, carotenoids, vitamins, proteins,fibers, and mineral elements.21 Samplepreparation techniques for BFR extraction include QuEChERS,1 dispersive liquid–liquid micro-extraction,solid-phase extraction (SPE), solid-phase micro-extraction, and otherapproaches use adsorbent-based techniques for testing new synthesizedmaterials such as QuEChERS with magnetic nanoparticles.22 These new trends of procedures, using magneticnanoparticles, have evolved, gained visibility, and grown due to thesuccessful results. In addition, the main attributes were organicsolvent-free/reduction, small amounts of adsorbents, fewer steps,and less time and energy.22 The authorsalso showed that these magnetic nanoparticle adsorbents, mainly theones with particles with a 200 nm average size, presented an adsorptionability toward pigment matrix and other co-extracts from strawberrysamples. This type of adsorbent has also shown a set of successfulapplications when applied in the pre-concentration of BFRs in otherred fruit samples (blueberry and raspberry).2 Some authors reported the use of graphene materials in several extractionmethods for pesticide analysis in food samples.25 Recently, Zhenget al. reported the synthesized and successful use of ZIF-8@nitrogen-dopedreduced graphene oxide as a coating material for the extraction ofhalogenated flame retardants in crayfish.26 Another application using graphene oxide-based surface molecularlyimprinted polymers was reported for organophosphate flame retardantsin environmental water.27 Khetagoudar etal. reported the excellent performance of a graphene nanocompositein the elimination of pigments in green chili matrices.28 To the best of our knowledge, studies in whichgraphene-type materials [reduced graphite oxide (rGO) and sulfur-dopedgraphene (S-GF)] are applied for QuEChERS extraction of BFRs fromfruits/vegetables are not reported in the literature. It is, therefore,imperative to innovate and develop new methods to meet the needs forsample integrity, rapid analysis, cost-effective, and environmentallyfriendly methods, precision, and reproducibility. Also, no MRLs havebeen established for BFR, but the European Commission recommendedtheir monitoring in food.29Some BFRs are present incomplex matrices in vestigial amounts,such that they cannot be simply detected. Complex samples are challengingand require more attention, and many limitations need to be exploredto mitigate matrix effects that analytical chemists must overcome.Thus, challenges can be met by skillful sample pre-concentration ofseveral compounds simultaneously prior to target analyses. The approachesshould be tailored to study matrix interferences and produce effective,reliable, and accurate methods for extraction and analysis. The Capsicum cultivars) witha high content of pigments (carotenoids), spicy compounds (capsaicinoids),fatty oils, protein, mineral elements, and so forth. Moreover, thepossible contamination of the target analytes [polyBDE (PBDE) congenersand novel BFR] conditioned in plastic packaging was also explored.Here,for the first time, an analytical approach developed to meetthe demands using different dispersive SPE (d-SPE) sorbents, namely,synthesized graphene-type materials (rGO and S-GF), was evaluatedto meet the challenge of removing the interferents from a complexfood sample , and the acetonitrile was obtained from CarloErba . The QuEChERS EN method and bulk sorbents,namely, primary secondary amine (PSA), C18-silica, and carbon, wereobtained from Agilent Technologies . The carbon bulk specificationsdescribed that the average particle size was 40–120 μmand irregular. A working standard mixture of the contaminants containinga total of 12 BFRs was prepared at 150 μg/L in n-hexane. This mixture was used to prepare spiked and calibrated standardsolutions in n-hexane. Data and statistical analysiswere carried out using GraphPad Prism 6.0 and Excel software.The standards of BFRs (sevenPBDE congeners and five novel BFRs) with high purity (≥97%)were purchased from Isostandards Material, S.L.  andstored in a freezer. The 12 compounds were 1,2-dibromo-4--cyclohexane(TBECH), pentabromotoluene (PBT), 2,4,4′-tribromodiphenyl ether(BDE28), pentabromoethylbenzene (PBEB), 2,2′,4,4′-tetrabromodiphenylether (BDE47), 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB), 2,2′,4,4′,5-pentabromodiphenylether (BDE99), 2,2′,4,4′,6-pentabromodiphenyl ether(BDE100), 2,2′,4,4′,5,5′-hexabromodiphenyl ether(BDE153), 2,2′,4,4′,5,6′-hexabromodiphenyl ether(BDE154), 2,2′,3,4,4′,5′,6-heptabromodiphenylether (BDE183), and 1,2-bisethane (BTBPE).The internal standard (IS) 5′-fluoro-2,3′,4,4′,5-pentabromodiphenylether was also obtained from Isostandards Material, S.L. . The 2.231 Briefly, the rGO preparationconsisted, in the first step, the addition of 10 g of graphite andover 200 mL of fuming HNO3, keeping the mixture at 0 °C.Then, 80 g of KClO3 was gradually added over 2 h; afterward,the mixture was stirred for 21 h, maintaining the temperature of 0°C. The graphene (GO) material obtained was filtered and washedwith water until a neutral pH was reached and then dried under vacuumat room temperature. In the second step, the GO was exfoliated ina vertical quartz reactor under a nitrogen atmosphere by heating at10 °C/min to 250 °C and keeping this temperature for 30min; then, the temperature was increased from 250 to 700 °C usingthe same heating rate, and then this temperature was maintained for30 min. At the end of the process, the rGO material was obtained.31 The S-GF was prepared by milling 0.5 g of commercialgraphene flakes (GF) together with 0.15 g of elemental sulfur in ballmilling equipment  for 5 h at a frequency of 15 s–1 using two zirconium oxide balls (1.5 cm in diameter).The obtained material was then pyrolyzed in a nitrogen atmosphere,heated up to 600 °C at a heating rate of 2 °C/min (Nabertherm),and maintained at this temperature for 1 h.30The graphene-type materials were prepared by proceduresalready reported.Supporting Information file.The prepared materials were characterized by several techniques,such as Raman, XPS, XRD, SBET, and TEM. All details  regardin2.3Capsicum(C.) annuum L., Capsicum frutescens L., and Capsicum chinense (packagedand stored in plastic containers) were purchased in Porto, Portugal,at local supermarkets. The samples were separately frozen at −20°C. Each sample was coldly homogenized using a high-performanceblender . The grinding of the sample was performedat the maximum speed of the equipment (speed 10) for 10 s; then, thesample was removed from the walls of the container, and the samplewas ground again at a speed of 10 for 10 s. After this sample preparation,the samples were frozen and stored in the same package until extractionand analysis.A total of 20 samples of 2.4n-hexane. The IS was added at a constant concentration foranalytical quality control immediately before injection. After vortexing,the sample was ready for gas chromatographic analysis.Samples(10 g) were mixed with 10 mL of acetonitrile in a 50 mL Falcon tube.Subsequently, EN QuEChERS salts were added, and the sample was vortexedfor 1 min. The tube was centrifuged for 5 min at 4500 rpm. 1.5 mLof the upper layer was transferred to a 2 mL microtube with the additionof different sets of sorbents 1. The mi2.4.132 and EURACHEMguidelines:33 linearity with a matrix-matchedcalibration curve, matrix effect, recoveries, the limit of detection(LOD), the limit of quantification (LOQ), and repeatability and reproducibility.The LOD and LOQ were calculated based on the standard deviation ofthe signal and the slope of the calibration curve. The matrix effectsand intra-day and inter-day precision were calculated according toFernandes et al. 2020.2 The C. annuum L. extract spiked with each of the BFRsat seven concentration levels (μg/kg) (ranging between 0.10and 1.88 μg/kg) was prepared for the establishment of the calibrationcurve. For each level, the determinations were performed in triplicateunder optimal conditions. The recovery and repeatability of 12 BFRswere determined to evaluate the method’s performance in C. annuum L. The repeatability and trueness of themethod were studied by carrying out six consecutive extractions atthree concentration levels .The analyticalperformance of the gas chromatography system with an electron capturedetector (GC-ECD) was carried out through the following parametersbased on SANTE/11813/20172.51 Briefly, the gas chromatography conditions were as follows:the injector temperature was 250 °C; the initial oven temperaturewas 90 °C (held for 1 min), which was then increased to 150 °Cat 16 °C/min (held for 1 min) and then to 290 °C at 16 °C/min(held for 30 min); and the gas chromatography detector was maintainedat 300 °C. The splitless injection was adopted throughout thewhole experiment. The method validation and all the analyses wereperformed in GC-ECD. GC/MS analysis with a Trace-Ultra GC  coupled to an ion trap mass detector,Thermo Polaris, was performed at the same conditions as GC-ECD inall the positive samples observed in GC-ECD in order to have confirmation.Data acquisition was performed first in the full scanning mode from50 to 500 m/z to confirm the retentiontimes of the analytes. All standards and sample extracts were analyzedin the selective ion monitoring (SIM) mode and tandem mass spectrometry(MS/MS). The SIM ions selected for the PBT confirmation were 486,328, and 326, and the precursor ions for MS/MS were 486 and 326.Analysiswas performed on GC-ECD equipped with a Zebron-5MS fused silica capillary column (30 m ×0.25 mm i.d. × 0.25 μm film thickness)  used for separation and ultrapure helium (purity ≥ 99.999%)used as the carrier gas at a flow rate of 1.0 mL/min. Chromatographicdata were recorded and processed with Shimadzu’s GC Solutionsoftware. The parameters were according to those.2.6ANOVA statisticalanalysis was performed to estimate significant differences among differentanalytical procedures using GraphPad software.33.131 here, a summary of the main aspects of their characterization isgiven for the sake of the reader to avoid labyrinthic access to data.The rGO was characterized by several techniques, namely, N2-adsorption isotherms, XRD, TEM, XPS, and Raman spectroscopy.31 The surface area determined by the BET methodto N2 adsorption isotherms  was 867 m2 g–1, which suggests the formation of a few-layer graphene structurefor rGO. The average pore diameter was found to be 7.9 nm by the BJHanalysis . The XRD corroboratedthe formation of a few-layer graphene structure (average stackingnumber of 12 layers) with an interlayer distance of 0.34 nm. The rGOTEM micrograph  showed thepresence of winkled structures of graphene consisting of 5–12graphene layers. The characterization of the rGO composition by XPSanalysis  indicated a surfacecomposed of carbon and oxygen . Raman spectroscopyis widely used for the characterization of carbon materials , especially because conjugated and double carbon–carbonbonds lead to high Raman intensities.34 The stretching of the C–C bond in graphitic materials givesrise to the so-called G-band Raman feature, which is common to allsp2 carbon systems (∼1580 cm–1). The G-band is highly sensitive to strain effects in sp2 nanocarbons and can be used to probe any modification to the flatgeometric structure of graphene. The D band (∼1350 cm–1) is significant in providing information about the electronic andgeometrical structures through the double resonance process.34 The intensity ratio between the D and G bands, ID/IG, is often usedto estimate the disorder degree of graphitic materials.36Even though these two graphene-type materials werepreviously preparedand their characterization was reported in the literature,ID/IG) asa quantitative indicator of the amount of disorder or edges of therGO structure, which was calculated as 0.63.By Raman spectroscopy, the degree of disorder in the structureof graphene was studied using the intensity ratio of the D and G bands revealeda BET surface area of 284 m2 g–1, whichwas appointed to the piling up of some graphene layers in the S-GFstructure. The average pore diameter was determined by BJH analysisgiving a value of 3.8 nm .The reported XRD pattern of S-GF indicated an interlayer distanceof 0.34 nm and a stacking number of graphene layers of 32, suggestingthe formation of a graphenic material with some aggregation of thegraphitic layers, following the outputs of the N2-adsorptionisotherms analyses. The TEM images of S-GF  showed graphene sheets with some folding mainly at theborders and with sizes in the range of hundreds of nanometers to afew micrometers. The surface composition obtained by XPS  revealed that S-GF contains 97.5%of C, 1.7% of O, and 0.8% of S, confirming S-doping. The Raman spectroscopyrevealed an increase in defect density and disorder due to the S-dopingprocess , as indicatedby the significant increase in the ID/IG ratio obtained for S-GF (1.72 vs 0.61 forundoped GF).Regarding the S-GFmaterial, the NSBET than rGO(284 vs 867 m2 g–1). Although both materialsshowed mesoporous properties, the rGO has a lower stacking of graphiticlayers (NL = 12 vs 32 for S-GF), whichresults in a higher surface area. This difference is most likely dueto the completely different starting materials used in their preparation—commercialGF for S-GF and graphite for rGO. The commercial carbon bulk alsotested was not characterized. Table S1 summarizesthe graphene-type material’s properties.Comparing the rGO and S-GF materials, beyond theS-doping, theS-GF presents a smaller 3.222 Cleanup sorbentslike PSA, C18, and commercial carbon bulk were commonly applied inthe second step of the QuEChERS procedure.1 As the matrices are diverse and complex, some work has emerged,namely in the application of new sorbents.38 Some studies reported that commercial d-SPE, with the use of carbon,presented lower efficiency for planar compounds.39Duringthe QuEChERS procedure, different sets of dispersive sorbentswere used in several applications.4, C18, and PSA. The chromatogramsobtained with different cleanup sets are shown in 4 + PSA + C18 + carbon) is insufficientat removing interferences and during the extraction, the efficiencyof the extraction was influenced and reduced. It was observed thatchromatogram B compared with C and D shows fewer interferences, andeven most of them have disappeared, suggesting that MgSO4, PSA, C18, and a small amount of graphene-sorbents effectively removeco-extractive interferences from the matrix. As previously demonstratedby other authors, graphene and other graphene-type materials showedvery promising results, even though only studies with pesticides havebeen reported.42In the present work, the ability to remove the co-extractiveinterferences was evaluated using lower amounts of graphene-type materialsorbents together with MgSO3.2.1The use of different graphene-dispersivesorbent materials (rGOand S-GF) was evaluated during the sample preparation process. Tobetter evaluate the performance of the two types of graphene materials,the extraction efficiency was evaluated through recovery studies.The recovery values obtained for the procedure using graphene materialswere compared with those obtained using commercial carbon bulk. 28 the present graphene-type materialspresented not only good removal efficiencies of pigments (extractbecame colorless after the cleaning step with graphene compounds)in Capsicum samples but also excellentcleanup ability for other compounds of the matrix, as you can seein 3O4) as a sorbent in tobaccosamples.42 The G/PSA/Fe3O4 presented a transparent, few-layer structure by TEM and SEMwith a lower BET surface area.42 Otherauthors reported the excellent performance of a graphene nanocompositein the elimination of pigments in green chili matrices.28 However, these authors have not explored allthe morphological characteristics of the nanocomposite, so the studiescannot be compared.The graphene-dispersive sorbents showed a great improvement inthe efficiency of the extraction procedure of the target 12 BFRs.We found that graphene-dispersive sorbents did not adsorb the BFR,while commercial carbon presented some adsorption that was verifiedby the reduction in recovery. The layered structure of graphene-typematerials can explain the advantage of these materials concerningthe irregular and disordered structure of commercial carbon. As alreadyreported for graphene,3.2.2Capsicum extracts when compared with d-SPE with commercialcarbon. Significant differences were confirmed. However, no significantdifferences between the recoveries obtained using 2 or 5 mg of graphenesorbents were observed. The chromatograms obtained using 5 mg of graphenesorbents showed better purification, and that is why this was theselected amount in the optimization study (In addition to the differences in the results obtainedbetween different graphene-dispersive sorbents (S-GF and rGO), theamount of each sorbent (2 and 5 mg) was also studied. on study 1.NL = 12 vs 32 forS-GF). These properties revealed the main role in improving the purificationcapacity. Therefore, cleanup set 5 (CL5) with 5 mg rGO, 150 mg MgSO4,50 mg C18, and 50 mg PSA was chosen for further studies.In addition, rGO showed slightly better results than S-GF,whichcan be explained by its higher BET surface area and a lower stackingof graphitic layers was prepared for the establishment of the matrix-matched calibrationcurve. The analytical parameters such as linearity, LOD and LOQ, recoveries,matrix effects, precision, and uncertainty were studied (n = 3)at three spiked levels  chosen consideringthe LOQ values , thuscovering the range of LOQ values. For each level, the extraction ofBFRs in the Capsicum sample and thedeterminations were performed in triplicate under optimal experimentalconditions. The mean recoveries between 90 and 108% were achieved.The precision was evaluated through intra- and inter-day studies,and the results were less than 14% RSD. The uncertainty was also evaluatedfor the 12 BFRs and was in the range between 4.9 and 18.4%, followingthe requirement (50%) of the EU guidance document SANTE/11813/2017.3.The details of the uncertainty studies are summarized in Table S2 in Supporting Information. In termsof the matrix effect, most of the compounds show a positive effect,resulting in a signal enhancement. Signal suppression was only observedfor three compounds , with values ≤−20%, which showed a very low suppression effect. The enhancementeffect was observed for the remaining compounds and between values(19–35%). The use of these graphene-type materials in the cleaningstep allowed for moderate matrix effect values. The opposite was demonstratedby Fernandes et al.,1 who reported a muchhigher matrix effect using a classical QuEChERS extraction methodusing commercial sorbents. The method demonstrated good accuracy,precision, and robustness and can entirely comply with the detectionrequirements for BFR.The  studied 2. Good l3.4Capsicum samples that were purchasedat the local market and which were packaged in 100 g plastic containers.The samples were extracted and analyzed in triplicate. The attainedresults demonstrate the absence of PBDE in all the samples. However,PBT was quantified in two samples at a concentration of 0.71 and 0.79μg/kg. The results showed RSD between 5 and 11%. Confirmationof the presence of PBT in the two samples was achieved by GC–MSand GC/MS/MS.The optimized and validated QuEChERS-graphenedispersive sorbent-GC method was applied to the analysis of the BFRin 20 3.5Capsicum annum L. matrices, and that is why comparisonwith other works is more difficult. Table S3 presented in the Supporting Information summarizes some studieson BFR analysis in food. A comparison of the present study with theonly analytical method based on QuEChERS methodology for the extractionand determination of BFRs in Capsicum cultivars was performed,1 and the presentmethod showed significantly better recoveries for all the BFRs (90–105%)in comparison with 66–104% for the published work.1 Furthermore, the LOD (0.10–0.23 μg/kg)of the developed method was significantly lower than that of the abovementioned method (1.4 and 9.3 μg/kg).1 We can also add a comparison of this method with others performedin BFRs and red fruit samples,2 and wealso concluded that the analytical parameters  were improved in this method. Other works on different food matricesusing other extraction techniques also showed lower extraction efficiencyfor BFRs than the present method and higher RSD.43 Other studies, mostly in fish samples, are also reportedin the literature.47 Comparisons are complicated because fish and related samples presentdifferent compositions when compared with our sample (Capsicum cultivars), namely in the amount of fat.However, comparing the analytical parameters, this new approach presentedbetter values of recoveries, LOD, and LOQ.To the best of our knowledge, this is the first methodreported for the simultaneous analysis of 12 BFRs in Capsicum cultivars using a QuEChERS approach coupled with a cleanup stepadding lower amounts of graphene-type material to the dispersive sorbents.Due to the combination of the classic sorbent’s propertieswith graphene-type materials, they were capable of removing complicatedinterferences present in the Capsicum cultivars with higher effectiveness. The major potential of thismethodology is that, when compared with the classical extraction method,the studied graphene materials added an extra cleaning to the extract,showing excellent purification performance with lower amounts of sorbentsnot influencing the high extraction efficiency. We also conclude thata complete characterization of the materials used as sorbents evidencedin this work is crucial and will allow advances in the developmentof methods. rGO provided the best results and presented the lowestnumber of layers and a high BET surface area, which led to the conclusionthat these properties are the ones that allowed better performances.In this study, wepresented a novel way to cleanup the Capsicum cultivar samples. As apromising cleanup material, graphene-type materials have future applicationpotential to overcome hurdles associated with challenging matricesin detecting multiple contaminants in different samples.The results revealed that this is a simple, sensitive, quick, robust,and effective modified QuEChERS method for the detection of BFR residuesin