Higher specific surface area graphene nanoplatelets (NP3) exhibit reversible capacity up to 505 mA h g−1 in the first discharge cycle (29.5% higher than that of graphite). Although significant irreversible capacity is shown for NP3, still higher reversible capacity is obtained compared to that of graphite electrode. The presence of micropores in the graphene structure benefits the lithiation. C-rate capability tests also show better performance of the graphene-based electrode. In this work, we demonstrate that graphene nanoplatelets with high specific surface area (714 m2 g−1) improve the electrochemical performance of Li-ion battery electrodes. The relationship between specific surface area, the presence of defects, and porosity is discussed.In order to understand the influence of the morphological properties of graphene materials on the electrochemical performance of electrodes for lithium-ion batteries, three different graphene nanoplatelets with the increasing specific surface area (NP1: 296 m Howeverirements . The useDue to its outstanding properties, such as high electrical and thermal conductivity and good mechanical strength, graphene will play an important role in the development of new generation of batteries. Since its first isolation in 2004 by Recent studies demonstrate the benefits of using graphene in anode formulation for Li-ion batteries as it can act as active on a non-active material. 3D graphene materials with diverse architectures [graphene balls , fibers −1) after 30 cycles with 82.6% capacity retention was obtained (4 nanoparticles into the micropores of MCMBs (mesocarbon microbeads) 4 inside the micropores, producing a decrease of the SEI formation, accommodation of electrode expansion, and a stable cycling performance due to the encapsulation. With these results, the benefits of the use of hybrid materials for anode preparation are demonstrated.Ternary Sn–Sb–Cu alloy nanoparticles with a specific hollow structure and uniform particle size of 10–20 nm have been described by Yang et al. as an anode material for lithium-ion batteries. A relatively high electrochemical capacity (380 mAh gobtained . During robeads) . The eleTwo-dimensional graphene-based materials such as graphene nanoplatelets (GNPs), graphene nanosheets, or reduced graphene oxide (rGO) have also been studied. A series of graphene nanosheets obtained from both thermal exfoliation and wet chemical reduction in different reducing agents were studied by −1  from Nanografi Nano Technology are used to evaluate the influence of the specific surface area on the electrochemical performance of electrodes for lithium-ion batteries. GNPs have different specific surface areas and a similar layer lateral size and composition. GNPs were used as an additive in the electrode formulation together with graphite  and carbon black Super C65 . All materials were used as received.−1 by flowing air, to determine graphene impurities and the oxidation temperature of graphene nanoplatelets. Specific surface areas were determined with Micromeritics ASAP 2020 using N2 gas as the adsorbate.Transmission electron microscopy (TEM) (JEOL JEM-1010) was used to examine the size and morphology of graphene nanoplatelet layers. Raman spectra were obtained from JASCO NRS-5100 applying 532 nm laser light to determine the presence of defects, and elemental analysis (LECO CHNS 932) was carried out to analyze the material composition. Thermogravimetric measurements (Mettler Toledo TGA 2) were performed between 0 and 900°C at a heating rate of 10 K minThe electrode was prepared by first making a slurry by mixing the active materials (graphene nanoplatelets and graphite) with conductive carbon black Super C65  in a weight proportion of 94.5:1. When graphene-based electrodes were prepared, the corresponding wt% was added to the slurry formulation and the same amount of graphite was taken. For full graphite electrodes, 94.5% by weight was used. A mixture of carboxymethyl cellulose and styrene-butadiene rubber (CMC-SBR) dissolved in water was used as a ligand in a weight proportion of 4.5% to maintain the active materials fixed. The obtained slurry was used for coating the electrodes on a Cu foil of 12 µm (MTI) using a “doctor blade” technique. Further annealing for 30 min at 60°C and 30 min at 110°C was carried out.2O < 0.2 ppm and O2 < 0.2 ppm, Mbraun). The diameter of electrodes and separator is 18 mm. The half cells were assembled with a glass fiber separator (Whatman GF) impregnated by electrolyte solution 1M LiPF6 in a 1:1 (v:v) mixture of ethylene carbonate (EC) and dimethyl carbonate (DMC) (Solvionic). A disc of lithium metal was used as a counter electrode (99.9% Goodfellow). Electrochemical characterization was performed using an eight-channel battery tester from Neware (BTS4000). The cells were galvanostatically charged/discharged at various C-rates between the cut-off voltages of 0.003 and 2.1 V. All the electrochemical tests were performed at room temperature. The mass loading of the active materials was taken into account to calculate the capacities.The cells were assembled in a high-purity argon-filled glove box  and increases to 0.63 for NP2 with 470 m2 g−1 and 0.81 for the highest surface area graphene . The increase of ID/IG ratio is also associated with the presence of oxygen in the structure. D/IG ratio observed for NP3 together with the highest specific surface area and bigger pore size distribution compared to NP1 and NP2 indicates the presence of more defective and disordered carbonaceous structure which is beneficial to improving the lithium storage capacity  can be observed for electrodes based on graphene nanoplatelets. All the results shown in this study correspond to electrodes containing 10 wt% of the corresponding graphene nanoplatelets in the formulation. The total active material mass loading including graphene and graphite is fixed to 94.5 wt%. The results corresponding to different graphene mass loading will be indicated explicitly. The zoomed-in discharge curves for graphite, NP1, NP2, and NP3 electrodes can be seen in the inset of +) are associated with intercalation/de-intercalation processes in carbonaceous materials.The surface area effect on the electrochemical performance of graphene-based electrodes for LIBs was evaluated using galvanostatic charge–discharge cycling. During the first discharge curve at slow C-rates (C/20) shown in +) can be observed. It is associated with the first interlayer graphene sheet Li intercalation that occurs at a higher potential compared with plateaus placed below ∼0.25 V (vs. Li/Li+) , a redox process at ∼0.8 V (vs. Li/Li Li/Li+) .+) in all materials. As reported previously by Stournara et al. using first principle calculations, the lithiation of epoxide groups takes place at those high potentials (6). The greatest capacities are achieved for this oxygen content range with lithiation potentials close to ∼0.8 V (vs. Li/Li+). Due to the strength of C–O bonds, the lithiation potentials are relatively higher than the graphite lithiation potentials. The bigger interlayer space produced by disordered and defective carbon also increases the capacity in the first cycle.On the contrary, an almost negligible capacity is obtained at potentials ≥1.4 V . Also, taking into account the elemental analysis (+)  .−1, respectively. The lithiation capacity in the first cycle for the NP1 electrode is similar to that of the graphite electrode (390 mA h g−1). An increase of 29.5% for the NP3 electrode is observed indicating the good effect produced in the electrochemical performance by the high surface area present in the NP3 material.Capacity values obtained in the first discharge for NP1, NP2, and NP3 electrodes are 388, 420, and 505 mA h gNevertheless, irreversible capacity loss in the first cycle, corresponding to surface reactions and SEI formation, increases also with the GNP surface area, being 17, 21, and 31% for NP1, NP2, and NP3, respectively. According to the previous observations reported , these rIn −1 is obtained for the NP1 electrode in the first cycle with low fading capacity after the fifth cycle (307 mA h g−1). For electrodes composed of graphene materials with more specific surface area, the capacity increases. In case of the NP3 electrode, the reversible capacity obtained is 327 mA h g−1 in the first cycle, maintaining this value (320 mA h g−1) after five cycles (at C/20). The value of the specific reversible capacity for the NP2 electrode is between NP1 and NP3, 318 mA h g−1, retaining 315 mA h g−1 at C/20 after five cycles. In the case of graphite, the specific reversible Li-capacity recorded for the first cycle is 315 mA h g−1, and no fading capacity is observed in the fifth cycle (314 mA h g−1) at a current rate of C/20, as expected.−1 after five cycles at C/5. These can be attributed to the enhancement produced by the presence of highly conductive graphene nanoplatelets in the electrode composition. These results indicate that highly disordered carbon in the GNP structure results in a boost of the specific capacity of anodes for lithium-ion batteries. The addition of 10 wt% of huge surface area GNP in the electrode composition represents an increase in the capacity of about 4%.Additionally, good C-rate capability is observed for all GNPs, especially for NP3 retaining 290 mA h g−1 (at a C-rate of C/20) was achieved in the first discharge cycle indicating the influence on the lithiation capacity improvement caused by the high surface area GNP. According to the behavior observed for the 10 wt% NP3 anodes, a highly disordered graphene structure carries a significant irreversible capacity, which is 69% for the 50 wt% NP3 electrode, but still retaining up to 368 mA h g−1 in the first cycle after SEI formation , the specific reversible capacity is improved by a factor of 4%, and it will help to go further to the theoretical graphite capacity.−1 with 100% coulombic efficiency.The specific capacity retention and coulombic efficiency for the NP3 electrode during the cycling stability test are shown in The mechanism of Li insertion/disinsertion by graphenic carbon materials is still not well-established. Contradictory reports concerning lithium mechanism in graphenic materials can be found. Also, huge variation in the reversible capacity has been reported for similar graphene-based materials. This lack of consensus has been mainly related to the wide variations in the structural characteristics, such as the number and types of defects and the degree of ordering. In order to compare NP3, evaluated in this study, with other graphene-based electrodes reported in the literature, −1 of capacity  were evaluated. Morphology and layer lateral size distribution evaluated by analyzing TEM images show the same distribution for all graphene materials of 1.3 µm. An increase in the surface area introduces more defects on the graphene structure (the ID/IG ratio increases from 0.53 (for NP1) to 0.63 (for NP3) and 0.81 (for NP3)). A significant increase in the presence of microporosity on the NP3 graphene structure is also observed. The presence of large amount of extrinsic/intrinsic defects in the NP3 graphene structure and higher microporosity produce an enhancement in the reversible capacity up to 505 mA h g−1 in the first discharge cycle for electrodes prepared with 10 wt% of graphene, representing an improvement of 29.5% compared to that of only graphite-based electrode (390 mA h g−1). Nevertheless, irreversible capacity loss in the first cycle increases also with the GNP surface area, which is 17, 21, and 31% for NP1, NP2, and NP3, respectively. Although high irreversible capacity is obtained for NP3, an improvement of the reversible capacity compared to that of the graphite electrode after five cycles (at C/20) is obtained (320 mA h g−1). Additionally, good C-rate capability is observed for all GNPs, especially for NP3 retaining 290 mA h g−1 after five cycles at C/5. These results indicate that highly disordered carbon in the GNP structure results in a boost of the specific capacity of anodes for lithium-ion batteries.Morphological properties of graphenic materials have considerable impact on the electrochemical Li storage of graphene-based electrodes. In order to have a comprehensive understanding of how their structural and compositional features influence the electrochemical performance of electrodes, a series of graphene nanoplatelets with the increasing specific surface area (NP1: 296 mFrom this study, we conclude that the presence of extrinsic/intrinsic defects in the graphene structure is responsible for this enhancement of the reversible capacity. By tuning the wt% of graphene in the electrode formulation, the electrochemical performance of the batteries can be modified depending on the target application. From the industrial point of view, an accurate understanding of the influence of graphene morphological properties on the electrochemical performance of electrodes for Li-ion batteries is crucial. Nowadays, graphene nanoplatelets are sold in large scale by quite a lot of manufacturers around the world. Many different types of graphene nanoplatelets with specific physicochemical and morphological properties can be chosen. Understanding the influence of each of these properties and the proportion on the electrochemical behavior of electrodes for Li-ion batteries will help to select the most adequate graphene material for a given application.


Primary care providers (PCP) - internists, family practitioners, nurse practitioners, physician assistants - play an integral role in the care of older adults, although many receive limited geriatrics education. We sought to examine what questions community-based PCPs had about geriatrics and clinical care of older adults. As part of large clinical continuing medical education (CME) conferences across 12 states , PCPs attended a live in-person 60-minute geriatrics-focused lecture and entered questions into a mobile application. Questions were then qualitatively analyzed using constant-comparison and tie-break methodology. At all sites, 103 questions were asked with 158 upticks (PCPs could check off that they had similar question) with a range of 3-18 questions per lecture. PCPs asked questions on the following common themes: 1.) Medication-related , 2.) Dementia  3.) Medicare Coding 4.) Falls 5.) Weight loss, and 6.) Insomnia. There were a number of questions referencing incorrect practices . In conclusion, community-based PCPs nationally experience gaps in geriatric knowledge and several utilize practices that could jeopardize older adult health. While attending CME-based lectures is one means of overcoming these gaps, some PCPs may not find time or realize geriatrics as an educational need. PCPs need to be better supported with opportunities to ask geriatric care-related questions in order to improve the care of older adults.


In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in an increased consumption of the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior. Using a novel set of rewarding solutions, we directly compared contextual and gustatory ANC predictors in both food restricted and free-fed Sprague-Dawley rats. Our results indicate that, despite being food restricted, rats are selective in their eating behavior and show strong contextually-driven ANC similar to free-fed animals. These differences mirrored changes in palatability for the less preferred solution across the different sessions as measured by lick microstructure analysis. In contrast to previous research, predictive cues in both food restricted and free-fed rats were sufficient for ANC to develop although flavor-driven ANC did not relate to a corresponding change in lick patterning. These differences in the lick microstructure between context- and flavor-driven ANC indicate that the motivational processes underlying ANC generated by the two predictor types are distinct. Moreover, an increase in premature port entries to the unavailable sipper – a second measure of ANC – in all groups reveals a direct influence of response competition on ANC development. The sights, sounds and smells of a familiar kitchen while dinner is being prepared can evoke a strong drive to eat but in refraining from doing so one can reserve their appetite for the main course. Such consummatory choice behavior is also at play in foraging animals where decisions based on prior knowledge of territorial food sources can result in animals passing up a nutritionally-insufficient option for one of greater value that is likely available  a progressive devaluation of the first food source when anticipating a preferred option; 2) competing behavioral responses, such as spatial competition with the unavailable port, reducing the amount of time dedicated to licking/eating; and 3) active inhibition of the urge to consume the less preferred option despite animals, in some experiments, being motivated by food restriction. While interpretations based on data from variations of the ANC paradigm mostly support ANC resulting from a reward devaluation of the first food source  and condensed milk (solution 2) sequence for further establishing a contrast effect with nutritionally-relevant food sources. Interestingly, different parameters of licking behavior have been related to distinct motivational processes  and housed in pairs. The room was kept at 21 °C and humidity of between 40% and 70% under a 12 hour light- dark cycle (lights on at 7:00). Rats had free access to standard lab chow  and water. Prior to the experiment, half of the rats were put on a mild food restriction, and given 12.5 g of lab chow per day. This food restriction continued on experimental days but rats were put on a free-access diet during the weekends. For food restricted animals, daily food ration was given immediately following the day's behavioural session. All rats were weighed daily Monday through Friday and a percentage of baseline weights calculated. All testing was conducted in accordance to the Animals (Scientific Procedures) Act 1986 (PPL# PFACC16E2).2.2Animals were trained and tested in two identical operant chambers , each located inside a sound- and light-attenuated aluminum outer chamber (1200 × 700 × 700 cm). The behavioral chambers were equipped with a house light located on the left wall and 2 retractable sippers located on the right wall, which when extended fully were located approximately 1 cm behind the chamber wall. Sippers were accessed via ports  in the wall through which rats needed to poke their noses. This arrangement ensured that only the tongue could contact the sipper and prevented the formation of fluid bridges meaning that individual licks were recorded with high fidelity. Contact lickometers (Med Associates) were used to detect licks and ports were fitted with infrared beam breaks for detecting port entries. The house light was turned on at the beginning of each daily session and turned off at the end of it. Equipment was controlled by a computer running Med-PC IV Software Suite (Med Associates). Webcams were used to monitor the animals’ behavior.Animals were pre-trained for 10 min per day to lick a palatable 10% sucrose solution in all experimental boxes (Context A and B) for 6 days prior to the experiment. For experiments using a contextual predictor, a standard Med Associates box with clear plexiglass walls and a barred floor was used for Context A and a modified version with a striped wall covering, a fine wire mesh floor and continuous white noise (75 dB level) played on a speaker was used for Context B. Both sippers were extended simultaneously for 5 min, retracted for 20 s and presented again for a further 5 min. Licks were recorded from both sippers at this time to check that there was no location bias within the contextual behavioral paradigm.The ANC conditioning protocol  consisteFor the flavor preference test performed before and after ANC conditioning, two sippers each containing one of two flavors (grape or cherry) + 0.2% sodium saccharin were extended one at a time for a maximum time of 30 s, or 10 s after first sipper contact. Overall, 10 "forced choice trials" where only 1 sipper was presented at a time was followed by 30 "free choice trials" where both sippers were presented together. In the flavor preference tests, we recorded licks at each spout and analyzed the total licks for each solution in each type of trial (free-choice vs. forced-choice). At the end of the experiments animals were humanely culled via a Schedule 1 method.2.3Behavioral data (lick and port entry timestamps) were extracted from data files and analyzed using custom Python scripts that measured numbers of licks for each solution. All raw data files and the analysis scripts are available at the following link: DOI: 10.5281/zenodo.4772860. From these measurements we obtained and analyzed the following variables: Total licks (at each spout); Premature port entries; Licks per cluster ; and Total clusters . From these, we determined total licks in each phase, total head entries in both unavailable ports, number of lick clusters and licks per cluster were recorded for each of the 32 days (16 sessions). Lick microstructure was analyzed by using interlick intervals to divide licks into clusters. Clusters were defined as runs of licks with no interlick intervals > 500 ms 33.13.1.1n = 10) as evidenced by reduced consumption during phase 1 specifically on days when a more preferred solution was expected. Statistically, total lick measurements revealed a significant effect by ANC conditioning day (session)  = 6.20, P = 0.03) and interaction between session and Malt-Malt and Malt-CM days (condition)  = 4.62, P = 0.0003) (P = 0.11). As expected in phase 2, FF rats  = 36.70, P = 0.0002; Interaction: F = 9.17, P < 0.0001; Bonferroni post-hoc differences - Sessions 2 through 8). Using a novel sequence of rewards in the current study, these results extend previous findings that FF rats can develop robust ANC [We used a modified ANC paradigm with a novel sequence of rewarding solutions to gauge the effectiveness of contextual or gustatory predictors for enhancing contrast effects in free fed (FF) and food restricted (FR) Sprague-Dawley rats . When us 0.0003) A1-left.  FF rats A1-right bust ANC , 22.Fig.n = 10) also showed strong ANC (P = 0.001) and by conditioning day  = 21.94, P = 0.001) and an interaction between the two was also revealed  = 6.03, P < 0.0001). Post-hoc Bonferroni tests showed significant differences between control and experimental conditions on sessions 3 through 8. These results are consistent with a recent within-subject ANC demonstrating that contextual cues are sufficient for ANC to develop in FR rats, albeit using a different sequence of rewards P = 0.0013; Sessions: F = 21.94, P = 0.001; Interaction: F = 6.03, P < 0.0001; Bonferroni post-hoc differences –Sessions 3 through 8). Overall, these results indicate that contextual cues can act as effective signals for decreasing animals’ intake of a less palatable Malt solution in anticipation of a more preferred CM option whose intake increases when it is made available. Moreover, FR animals developed ANC after fewer conditioning trials (session 3) than FF animals (session 6) suggesting that despite being hungry FR rats can act selectively in their feeding behavior.FR rats  = 6.54, P < 0.0001; Interaction: F = 10.05, P < 0.0001; Bonferroni post-hoc differences –Sessions 3,4,6–8)  = 4.16, P = 0.0008; Bonferroni post-hoc differences –Sessions; 3–8; No main effect by Session: F = 1.88, P = 0.087)  A1 (FR: 2= 0.087) B1 furtheP = 0.006; Sessions: F = 4.39, P = 0.0005; Interaction: F = 3.36, P = 0.0041; Bonferroni post-hoc differences –Sessions 6,8)  = 11.64, P = 0.008; Session: F = 3.84, P = 0.002; Bonferroni post-hoc differences –Session 8; No interaction: F  = 0.66, P = 0.70). No differences for port 1 entries were seen in any condition  = 1.20, P = 0.30; Session: F = 2.87, P = 0.05; Interaction: F = 1.32, P = 0.29)  = 2.27, P = 0.05; Interaction: F = 0.58, P = 0.77) (These premature entry results are in line with data collected during the IPI phase where port entries to unavailable sippers 1 and 2 were measured for 20 s - IPI. On = 0.29) A2-left ( = 0.77) B2-left. 3.1.3P = 0.009; Session:  = 2.43, P = 0.03; Interaction:  = 3.72, P = 0.002; Bonferroni post-hoc differences - Sessions 6,7)  = 2.577, P = 0.14 and Session: F  = 1.41, P = 0.21)  = 4.46, P = 0.0004; Bonferroni post-hoc differences –Sessions 1,5,7; No effect for Condition: F  = 0.93, P = 0.36)  = 2.34, P = 0.03; Bonferroni post-hoc differences –Session 3,4; No effect for Condition: F  = 5.06, P = 0.05)  - is a measure commonly used to quantify the palatability of the reward (liking) while total clusters has been shown to relate to a reward's incentive value (wanting) as well as signal its post-ingestive feedback properties , 8; revions 6,7) A1-left.  = 0.21) B1-left.  = 0.36) A1-right  = 0.05) B1-right.P = 0.15; Session: F = 1.13, P = 0.36; Interaction: F = 0.76, P = 0.62)   = 3.91, P = 0.08; Sessions: F = 1.38, P = 0.23; Interaction: F = 1.02, P = 0.42)  = 2.82, P = 0.01; Bonferroni post-hoc differences – Paired Sessions 1,6; No main effect by Session: F = 0.72, P = 0.65)  = 1.42, P = 0.21; Interaction: F = 1.79, P = 0.10)  = 2.45,  = 0.42) B2-left.  = 0.65) A2-right  = 0.10) B2-right.In summary, when using contextual predictors, ANC was seen to develop in both FF and FR rats and this may be associated with a change in palatability of the non-preferred maltodextrin solution on experimental vs. control sessions.3.23.2.1n = 10) and FR (n = 10) rats showed ANC when different flavoring was added to phase 1 Malt solutions used to predict either Malt or CM in phase 2. Specifically, in FF rats  = 3.99, P = 0.001; Bonferroni post-hoc differences –Sessions 4,5; No Interaction: F = 1.28, P = 0.27). Similarly in FR rats  = 4.26, P = 0.0007; Interaction: F = 3.53, P = 0.003) and was apparent on sessions 4, 6–8 (Bonferroni post-hoc differences). As expected, phase 2 consumption was greater for both groups  = 0.69, P = 0.68; No Interaction: F = 1.31, P = 0.26)  = 2.91, P = 0.01; Interaction: F = 7.15, P<0.0001; Bonferroni post-hoc differences – Sessions 1–4; No effect by Condition: F = 5.06, P = 0.05). In summary these results demonstrate that when Malt is followed by CM gustatory cues are sufficient predictors for ANC development.We next tested whether gustatory cues can be used as effective predictors for ANC to develop. In contrast to previous results , 32, FF  FF rats A1-left,  FR rats B1-left t3.2.2P = 0.0003; Session: F = 2.22, P = 0.04; Interaction: F(7 63) = 3.70, P = 0.002; Bonferroni post-hoc differences –Sessions 2–8)  = 6.50, P < 0.0001; Interaction: F = 4.77, P = 0.0002; Bonferroni post-hoc differences – Paired Sessions 2–8)  = 31.47, ons 2–8) A1  B1.Fig. 6P = 0.006; Session: F = 4.71, P = 0.0003; Interaction: F = 3.39, P = 0.004; Bonferroni post-hoc differences – Sessions 4,5,7)  = 2.50, P = 0.02; Bonferroni post-hoc differences – Sessions 7,8; No significant Interaction: F = 1.26, P = 0.28)  = 0.94, P = 0.48; Interaction: F = 1.56, P = 0.17)  = 5.47, P < 0.0001; Interaction: F = 1.09, P = 0.38)  = 13.09, s 4,5,7) A2-right  = 0.28) B2-right. = 0.17) A2-left ( = 0.38) B2-left. 3.2.3P = 0.10; Interaction, F = 0.77, P = 0.61; main effect by Session: F = 4.42, P = 0.0005)   = 2.21, P = 0.05; Session: F  = 4.0, P = 0.001; Bonferroni post-hoc differences – Session 8; No main effect by Condition: F = 1.54, P = 0.24) . In phase 2, both FF and FR animals showed a session-dependent change in licks per cluster for CM compared to Malt  = 2.88, P = 0.01; No main effect by Condition: F = 2.69, P = 0.14; or by Session: F = 1.68, P = 0.13)   = 3.63, P = 0.002; Bonferroni post-hoc differences – Paired Session 4–8; No main effect by Condition: F = 4.83, P = 0.06 or by Paired Session: F = 1.04 P = 0.41) . Notably, these results show that in either motivational state (FF or FR) licks per cluster in phase 2 shifted from high to low levels with conditioning trials  = 3.29, P = 0.36; Session: F = 0.41, P = 0.89; Interaction: F = 0.51, P = 0.82)   = 0.25, P = 0.62; Session: F = 0.22, P = 0.98; Interaction: F = 1.06, P = 0.40)  indicating that changes in total clusters do not contribute to changes in phase 1 total licks. There was however a significant increase in phase 2 total clusters in response to CM for both FF and FR animals throughout conditioning  = 11.73, P = 0.008; Sessions: F = 2.90, P = 0.01; Bonferroni post-hoc differences – Paired Sessions 4–7; No Interaction: F = 1.68, P = 0.13)   = 31.07, P = 0.0003; Session: F = 2.75, P = 0.01; Interaction: F = 4.06, P = 0.001; Bonferroni post-hoc differences – Sessions 4–8)  which is in contrast to the changes in lick microstructure for contextually-driven ANC. These differences in the lick microstructure between animals using contextual  = 0.90, ntextual  and gustntextual  suggest 3.2.4P < 0.0001; Condition: F=2.12, P = 0.18; Interaction: F = 1.83, P = 0.21) indicating that there was no initial preference before conditioning and that licking to both flavors, irrespective of which flavor predicted CM, increased after conditioning  = 0.34, P = 0.56; Interaction: F = 0.35, P = 0.57)  C3. These3.2.5P = 0.0002; Session and Predictor: F  = 2.07, P = 0.04; No effect of Diet: F = 0.3132, P = 0.58). Post-hoc Bonferroni tests, however, did not show a significant different on any session between any of the groups. The results here, however, need to be carefully considered as the experiments using flavor and contextual predictors were not performed simultaneously.In the current study, four unique contrast conditions were tested . To formally compare each condition, we next analyzed the normalized phase 1 total lick data  to determine the effectiveness of each condition compared to one another in promoting ANC . A 3-way4Using a novel sequence of nutritionally-relevant rewards, in the current study we tested the predictive ability of contextual and gustatory cues on ANC and the motivational processes that underlie this behavior. Our results indicate that both contextual and gustatory information are effective predictors for ANC to develop. The selective reduction of Malt consumption may be at least partially due to spatial competition between the two sipper ports as increases in premature port entries in phase 1 were significantly increased on experimental days. In contextually-driven anticipatory sessions, our lick microstructure analyses suggest that ANC may be determined by a change in the rewarding properties of the Malt solution that is in all other respects equivalent to the one presented on control days - the only difference being the context signaling the availability of CM in phase 2. In contrast, ANC driven by gustatory predictors was not mirrored by changes in the lick microstructure indicating that the contrasting effects seen here are perhaps driven by competing factors. Due to their biological relevance, gustatory cues can be robustly associated with food sources, potentially acting as strong secondary reinforcers that can compete with negative contrast effects , 32. SinPrevious research, however, has shown that within-subject ANC can develop without physical predictors but rather continuous alternating days alone can signal the different conditions (P = 0.02) suggesting an increase in the incentive value of the flavored Malt solutions – an interpretation which is consistent with the results of the flavor preference test. Thus, it is possible that the addition of a flavor to the maltodextrin solution in phase 1 enhances its palatability vs. a non-flavored maltodextrin solution. This change in Malt palatability may in effect be impacting the hedonic disparity between the two rewards by altering the incentive value of CM. Such changes are reminiscent of those seen in temporal discounting paradigms where a comparative analysis of two rewards separated by time can impact the incentive value of each [Stereotypical patterns of rodent licking behavior are thought to reflect different underlying motivational processes where the amount of licks in a cluster of continuous licks has been shown to relate to reward palatability (reward liking) while the amount of total clusters changes with incentive value (reward wanting) as well as signal its post-ingestive feedback properties . These results may be attributed to the novel food choice sequence  where the disparity in the hedonic value and nutritional content between the two was different than past investigations [The fact that contrasting effects are based on relative rather than the absolute value of the rewards make them sensitive to various factors. For instance, their value-based as well as temporal disparity can strongly impact contrast , 18, 37.igations , 18, 42.A number of different neural processes must be at play when animals learn to predict rewards of different hedonic value. The lick microstructure analysis performed in the current study suggests that gustatory and contextual predictors may be mediating ANC through different motivational or cognitive processes. Studies investigating the neurobiological mechanisms that underlie ANC have mostly focused on the changes in reward value that might contribute to ANC development. While dopamine activity encodes information predicting a future reward as well as the reward itself In summary, our results indicate that despite the potential benefit in taking an opportunistic feeding approach, food-restricted animals can use contextual predictors to act selectively in their feeding choice and that these changes may stem from learned changes in the hedonic properties of the readily available food source. Gustatory predictors can also be used to optimize intake of a preferred food option in both free-fed and food restricted rats but less effectively than contextual cues - a results that may be due to the high predictive strength of flavors linked to a food source that differentially impacts the underlying processes that drive ANC. Future investigation of the neural activity contributing to these motivational and cognitive changes will help elucidate the neurobiology that allows animals to optimize their foraging strategies.Jessica Hayes: Formal analysis, Investigation, Writing – review & editing. Celia Garau: Conceptualization, Formal analysis, Investigation, Writing – review & editing. Giulia Chiacchierini: Investigation, Writing – review & editing. Gonzalo P. Urcelay: Conceptualization, Writing – review & editing. James E. McCutcheon: Conceptualization, Formal analysis, Writing – review & editing, Funding acquisition. John Apergis-Schoute: Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, Funding acquisition.The authors declare no competing financial interests.


This functionalized graphene was confirmed with high atomic content of S (4.79 at % S) as well as the presence of C–S–C and N–H species on the L-cysteine functionalized graphene (FG-CYS). Raman spectroscopy evidently corroborated the modification of graphene to FG-CYS with an increased intensity ratio of D and G band, ID/IG ratio (0.3 to 0.7), full-width at half-maximum of G band, FWHM [G] (20.3 to 35.5) and FWHM [2D] (64.8 to 90.1). The use of ethanol as the reaction solvent instead of common organic solvents minimizes the chemical hazards exposure to humans and the environment. This direct attachment of multifunctional groups on the surface of pristine graphene is highly demanded for graphene ink formulations, coatings, adsorbents, sensors and supercapacitor applications.Functionalization of pristine graphene to achieve high water dispersibility remains as a key obstacle owing to the high hydrophobicity and absence of reactive functional groups on the graphene surface. Herein, a green and simple modification approach to prepare highly dispersible functionalized graphene via thermal thiol-ene click reaction was successfully demonstrated on pristine graphene. Specific chemical functionalities (–COO, –NH Graphene materials have sparked enormous attraction and interest from both the scientific and industrial community owing to the fascinating properties of graphene and its widespread applications across many technological fields, such as nanoelectronics, sensors, composites, coatings, batteries, supercapacitors and hydrogen storage . The ong2 carbons of pristine graphene, or by the formation of a covalent bond between organic molecules and the oxygen groups of graphene oxide, GO [2 carbon in the graphene framework appears to be a promising covalent functionalization approach that offers several benefits. It is highly efficient, simple to execute, insensitive to oxygen and water, has no side products and proceeds rapidly with high yield [Covalent attachment of organic functional groups to the graphene surface can be achieved either by chemical reaction of free radicals or dienophiles spxide, GO . The radgh yield . Severalgh yield ,10,11,12gh yield .2 honeycomb framework. In fact, limited reports were found on the direct functionalization of pristine graphene via thiol-ene click chemistry. Castelain et al. used thiol-ene reaction for a direct functionalization of the graphene surface with short chain polyethylene (PE) brushes which were successfully used to prepare graphene based high-density polyethylene nanocomposites [Surprisingly, up to now, the majority of the reports of functionalized graphene have primarily focused on GO and its reduced form, reduced graphene oxide (rGO), where the preparation methodologies usually involve the use of hazardous chemicals and toxic gases, with large quantities of chemical waste generated after the reactions . To perfmposites . Peng etmposites . In anotmposites . Althoug2 carbon of graphene via thermal thiol-ene click reaction, which is schematically presented in Herein, we present a simple, green and sustainable method to functionalize pristine graphene through thiol-ene click reaction to acquire water dispersible graphene materials with multiple functional groups that are important for many applications. The aims of this work are twofold: first, to improve an existing thiol-ene click reaction using more sustainable and green conditions for the functionalization of pristine graphene, and second, to demonstrate versatility of this method to generate graphene with multifunctional surface chemistry with different end groups including ester, amino, and thioether. The developed method is based on the covalent attachment of thiol molecules on the sp−1) was used throughout the work, unless otherwise stated.Graphene was obtained from a local company . L-cysteine , thionyl chloride , diethyl ether  2,2′-azobis-(2-methylpropionitrile) , ethanol  were used directly without prior purification. High purity milli-Q water (18.2 MΩ·cmEthyl esters of cysteine were synthesized according to a reported method . In briev/v) via sonication for 1 h. Subsequently, the sonicated mixture was purged with nitrogen gas for 30 min to create an inert environment. Then, L-cysteine ethyl ester and 2,2′-azobis-(2-methylpropionitrile) (AIBN) were added into the mixture with a further nitrogen gas purge for 30 min, followed by a 30 min sonication. After that, the reaction mixture was poured into a round bottom flask with an additional 30 min of nitrogen gas purge and heated in an oil bath at 65 °C under reflux conditions overnight. After the reaction, the as-synthesized product was washed thoroughly with ethanol and deionized water using centrifuge, dried in oven at 65 °C overnight, and stored for further characterization.Functionalized graphene with L-cysteine ethyl ester (FG-CYS), was prepared according to the adapted procedure reported by Yap et al. . In a ty−1 on a Nicolet 6700 Fourier Transform Infrared (FTIR) Spectrometer . Morphology of the materials was imaged using a scanning electron microscope  at an operating voltage of 10 kV and a transmission electron microscope at 120 kV . Chemical composition and chemical species were analyzed by X-ray Photoelectron Spectroscopy  equipped with a monochromatic Al Kα radiation source (hv = 1486.7 eV) at 225 W, 15 kV and 15 mA. XPS survey scans were performed at 0.5 eV step size over −10 to 1100 eV at 160 eV pass energy with peak fitting analysis executed using Casa XPSTM software. The core-level XPS spectra were calibrated at 284.8 eV. Raman spectrometer  with an excitation wavelength of 532 nm (mpc 3000 laser source) was applied from 500 to 3000 cm−1 with an integration time of 10 s for three accumulations to determine the vibrational features of pristine graphene, and thermogravimetric analysis (TGA) of functionalized graphene was performed at a heating rate of 10 °C/min in nitrogen atmosphere from 25 to 1000 °C on a METTLER TOLEDO TGA/DSC 2 instrument.FTIR spectra were collected at 500 to 4000 cmThe morphology of pristine graphene and the functionalized graphene was first examined using scanning (SEM) and transmission (TEM) electron microscopy, as shown in A simple and rapid water dispersion test was performed to examine the effectiveness of thiol-ene functionalization d–f. As e3/2 and S2p1/2 at around 164.1 eV and 165.2 eV, respectively, can be assigned to thioether sulfur bonded to carbon (C–S–C) species on the narrow XPS spectra of S2p of FG-CYS, and confirmed the successful attachment of the thiol groups from the thiol precursor via thiol-ene click reaction on the surface of the graphene [3/2 and S2p1/2 peaks with lower intensities deconvoluted at 164.8 eV and 166.1 eV, respectively, could be ascribed to C–S or S–S species on the surface of graphene [2, NH3+, N–H and C–N+, respectively [Chemical composition of the functionalized graphene was determined by XPS analysis  with thegraphene ,19. Meangraphene . Note thgraphene . High-reectively ,22. The ectively ,16,23. T−1, D band at around 1350 cm−1, and 2D band at 2700 cm−1 [−1) and a symmetrical 2D peak (~2700 cm−1) as clearly observed on the Raman spectra of Gr and FG-CYS samples. As depicted in −1 was detected on the Raman spectrum of FG-CYS, suggesting a certain degree of defect found on the surface of FG-CYS. This finding was in consistent with the average value of ID/IG ratio (a measurand of the level of disorder of graphene) of FG-CYS (0.7), which was higher than Gr (0.3), indicating more defects were experienced on the surface of FG-CYS than Gr due to thiol-ene click modification using thiol precursor, as shown in Detailed Raman analysis was performed to verify the modification created on the surface of pristine graphene and functionalized graphene, as illustrated in 700 cm−1 ,25. The −1 on the FTIR spectrum of the functionalized material, but not identified on the FTIR spectrum of pristine graphene [−1 (stretching of S–H group) in the functionalized graphene suggested that all the –SH groups in the thiol precursor had reacted with the sp2 carbon in pristine graphene through thiol-ene click reaction [−1 for the stretching of C=O in the ester group on FG-CYS. Peaks at about 1640 cm−1 (N–H bending), 1090 cm−1 (C–N stretching) and 1054 cm−1 (C–NH2 vibration) were also found on the FTIR spectrum of FG-CYS, implying successful grafting of the functional groups on the pristine graphene. Two common peaks at 2913 and 2846 cm−1, which can be attributed to the asymmetric and symmetric vibrations of C–H of –CH2 group, respectively, were also observed in the functionalized graphene [The obtained FTIR characterization results presented in graphene . This fireaction . Additiographene . Based oFurthermore, TGA was also conducted on pristine and functionalized graphene to qualitatively and quantitatively determine the presence of attached functional groups on the pristine graphene after the thermal thiol-ene click reaction. As presented in 2 carbon and the lack of reactive functional groups on the surface of pristine graphene, we successfully demonstrated an effective functionalization of pristine graphene through a green and scalable thiol-ene click modification to endow a highly dispersible graphene. A summary of our key findings with evidence supported by comprehensive techniques, as tabulated in Despite the key challenges of inertness of spTo date, functionalization of pristine graphene by covalent bonding has rarely been reported in relation to its derivative, GO, due to the lack of reactive functional groups on the pristine graphene surface . It is uNumerous attempts have been made in the last decade to introduce organic functional groups onto the surface of pristine graphene through thiol-ene click chemistry. The degree of functionalization can be quantitatively gauged using both bulk (TGA) and surface (XPS) characterization techniques, as summarized in Based on the bulk TGA characterization technique, L-cysteine was found to be more effectively grafted on FG-CYS (present study) than G-LCHa, as reflected by its lower functional group coverage of 113, compared to 137 carbon atoms per unit of L-cysteine molecule, as tabulated in Another example of direct functionalization on pristine graphene was manifested in G-CHI and GR-Cys, with 1 cysteamine molecule per 113 and 96 carbon atoms, respectively, based on the value of functional group coverage. Meanwhile, 1.13 at % N and 1.66 at % S were found on G-CHI, while 4.78 at % N and 4.52 at % S were detected on GR-Cys after the thiol-ene click modification ,16. In cDespite the growing body of work recently reported to functionalize graphene directly using thiol-ene click strategy, there are still numerous open research opportunities to address the graphene dispersion issue, to endow a better processability of graphene materials  with desired properties. Beyond the conventional chemical modification of graphene such as the thermal heating process, other methods including microwave irradiation, plasma etching, electrochemical modification or a combination of these methods could be explored as promising alternative routes to resolve the low reactivity of graphene. Based on our current work, functionalization parameters such as the ratio of graphene to thiol precursor, reaction time and temperature, could be tuned to accommodate a more effective grafting of functional groups on the graphene surface. The future direction of graphene functionalization may be structured towards room temperature modification of graphene, which can be feasibly achieved via the photoinitiated thiol-ene click approach. In addition, more research efforts should be dedicated to the optimization of functionalization methods to achieve not only the better dispersion of graphene, but also the scalability of processing of new graphene materials to be more economical.In summary, the synthesis of functionalized pristine graphene by a green thermal thiol-ene click approach using L-cysteine ethyl ester was successfully demonstrated. The use of ethanol in replacing highly toxic organic solvents in this click reaction provides a generic, green, and scalable approach to graft graphene with desired functional groups, which can be achieved by selecting different types of thiol precursors bound with functional groups including hydroxyl, ester and amine groups. Successful modification of pristine graphene with the thiol precursor was confirmed by Raman, FTIR, TGA and XPS analyses. This green modification process provides a significant contribution towards the scalable production of functionalized graphene due to a simple and scalable chemical route which is beneficial for many applications, such as biomedical, sensing, graphene polymer composites, inks, supercapacitors, etc.


TARDBP, forms aggregates in the motor cortex. This aggregate formation may be triggered by an increase in the TDP-43 level with aging. However, the amount of TDP-43 is autoregulated by alternative splicing of the TARDBP 3′UTR, and how this autoregulation is affected by aging remains to be elucidated. We found that DNA demethylation in the autoregulatory region in the TARDBP 3′UTR reduced alternative splicing and increased TARDBP mRNA expression. Furthermore, in the human motor cortex, we found that this region was demethylated with aging, resulting in increased expression of TARDBP mRNA. The acceleration of DNA demethylation in the motor cortex was associated with the age of ALS onset. In summary, the dysregulation of TDP-43 autoregulation by age-related DNA demethylation in the motor cortex may explain the contribution of aging and motor system selectivity in ALS.In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43), which is encoded by  In order to assess the effects of aging on the autoregulation of TAR DNA-binding protein 43 (TDP-43) and the potential effects of this on the role of TDP-43 in Amyotrophic Lateral Sclerosis (ALS), Koike et al examined post-mortem motor cortex tissue from ALS patients. They found that DNA demethylation in the autoregulatory region of the TARDBP 3′UTR, which encodes TDP-43, increased with age and was associated with the onset age of ALS and thus could be indicative of a role for dysregulation of TDP-43 autoregulation in ALS pathology. It has been speculated that an increase in the amount of causative proteins contributes to aggregate formation3. Thus, one pathological hypothesis of system selectivity in neurodegenerative diseases is that the amount of disease-causing protein is increased in the impaired system. In fact, alpha-synuclein levels have been shown to be increased in neuronal systems affected by alpha-synucleinopathy4. However, the association between the amount of the causative protein and aging is unclear.In neurodegenerative diseases with aging as a primary risk factor5. In more than 95% of sporadic ALS cases, the nuclear protein TDP-43 forms aggregates in the cytoplasm and is depleted from the nucleus in diseased cells6,8. Increased intracellular concentrations of TAR DNA-binding protein 43 (TDP-43) have been speculated to be a factor in this aggregate formation10. However, to date, the mechanism linking TDP-43, motor neuron selectivity, and aging has not been elucidated.Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that selectively impairs primary motor neurons in the motor cortex and alpha-motor neurons in the spinal cord, and similar to other sporadic neurodegenerative diseases, aging is a major risk factorTARDBP pre-mRNA 3′UTR, and the level of TDP-43 is strictly autoregulated via its alternative splicing13. An increased level of nuclear TDP-43 promotes its splicing to produce nonsense-mediated mRNA decay-sensitive TARDBP mRNA and reduce the level of TDP-4314. However, when the level of TDP-43 in the nucleus is reduced, this splicing is repressed, and the TARDBP mRNA levels are increased. Therefore, TARDBP mRNA expression is continually increased in ALS-affected cells with reduced nuclear TDP-43 levels14. Following the formation of cytoplasmic TDP-43 aggregates, which are presumed to reduce the TDP-43 level in the nucleus by either entrapping newly generated TDP-43 or inhibiting the nuclear transport of TDP-43, the progression of the disease accelerates16. Some mutations in the TARDBP gene can alter its alternative splicing and affect the autoregulatory mechanism18. However, in sporadic ALS, the factor triggering the disruption of this autoregulatory mechanism leading to increased TDP-43 expression and TDP-43 aggregate formation in the motor cortex is unclear.Nuclear TDP-43 binds the 19. Indeed, an accelerated epigenetic age based on DNA methylation is associated with the age of onset in ALS patients with C9orf72 expansion repeats20 and in sporadic ALS patients21. DNA methylation not only regulates gene expression but also affects alternative splicing26. Based on these observations, we hypothesized that the DNA methylation status of the TARDBP-3′UTR changes with age in the motor cortex, which in turn alters the splicing of the TARDBP-3′UTR in the direction of increased TDP-43 expression.Aging alters the methylation status of DNA. The DNA methylation status defines the epigenetic age independent of the chronological age. In age-related diseases, this epigenetic age contributes more than the chronological age to mortality and morbidityTARDBP 3′UTR. We found that the demethylation of this region inhibited the alternative splicing and increased the expression of TARDBP mRNA. Furthermore, in the human motor cortex, this region was demethylated with aging, and the degree of demethylation was correlated with the level of TARDBP mRNA expression. An accelerated DNA methylation age of the TARDBP 3′UTR in the ALS motor cortex was associated with a younger age of onset, suggesting its involvement in ALS pathogenesis.To explore this hypothesis, we used the dCas9 system to selectively demethylate the CpG region of the alternative splicing-related site in the TARDBP pre-mRNA and induces the alternative splicing of intron 6 (exonic intron) and intron 7 (3′UTR intron), leading to nonsense-mediated mRNA decay14. We found that 15 CpG sites were clustered around the 5′ splicing site of alternative intron 7. An analysis of publicly available data revealed that these CpG sites are moderately to highly methylated in the human prefrontal cortex   Fig. , c. In t36. In addition, the methylation-linkage diagram of the two youngest (middle-aged) and two oldest (elderly) individuals showed generally lower pairwise correlations in the elderly individuals  was applied to demethylate the target DNA region  was cut at the AflII site, and a guide RNA fragment was inserted using Gibson assembly master mix (New England Biolabs). Four guide RNAs were selected using Benchling (https://benchling.com/). To construct the DNMT3A-TARDBP-target vector, pdCas9-DNMT3A-EGFP (Addgene plasmid 71666) was cut at a BbsI site, and a guide RNA fragment was inserted in the same manner. The sequences of the guide RNAs are described in Supplementary Table To construct the TET1-21. During the analysis, one ALS patient was excluded due to the detection of a mutation in TBK1. To analyze the relationship between the DNA methylation levels of CpGs 10–15 in the motor cortex and age, we included the motor cortexes of three ALS patients and three controls and analyzed data from 10 ALS cases and 11 controls . Using 25 mg of human postmortem tissue, genomic DNA was purified using a DNeasy Blood and Tissue kit (QIAGEN). According to the manufacturer’s protocols, the purified genomic DNA was bisulfite treated with an EpiTect Fast DNA Bisulfite kit (QIAGEN). In both HEK293T cells and human postmortem tissues, bisulfite amplicon sequencing was performed using primer sets A and B . The sequenced reads were mapped to the human reference genome hg19 using the methylation analysis tool Bismark v0.18.1 (Babraham Bioinformatics)38. The CpG density at each CpG site was calculated by a kernel-density estimation (bandwidth = 10.73). Principal component analysis was performed using the average methylation rates, average pairwise correlations, and epipolymorphism scores of 3′UTR CpGs 1–9 and 3′UTR CpGs 10–15. The ‘pcaMethods’ R package54 was used to apply the nipals algorithm with unit-variance scaling.The epipolymorphism scores were calculated and methylation-linkage diagrams were generated based on a previous report5 HEK293T cells, the total RNA was extracted using a Nucleo Spin RNA XS kit (MACHEREY-NAGEL). First-strand cDNA was synthesized from the total RNA using Prime Script Reverse Transcriptase (TAKARA Bio). RT-PCR was performed using LA Taq (TAKARA Bio). The primer pairs employed for RT-PCR are listed in Supplementary Table From 2.5 × 10One patient with an unknown postmortem interval (control 9) was excluded from the RNA analysis , and centrifuged at 100,000 × g for 30 min at 4 °C. The insoluble pellet was dissolved in 100 μl of urea buffer  supplemented with a protease-inhibitor cocktail, sonicated , and centrifuged at 100,000 × g at 22 °C for 30 min. The supernatant was used as the urea-soluble fraction. The protein concentration of the RIPA-soluble fraction was measured using a BCA protein assay kit (Thermo Fisher Scientific). The protein concentration of the urea-soluble fraction was assumed to have the same ratio as the RIPA-soluble fraction. The supernatant was resuspended in Laemmli Sample Buffer (BioRad) and treated at 96 °C for 5 min. The proteins were separated by SDS-PAGE using a 10% polyacrylamide gel  and transferred to a PVDF membrane (Millipore). After transfer, total protein on the membrane was visualized using No-Stain Protein Labeling Reagent (Thermo Fisher Scientific). The blot was immersed in the primary antibody overnight at 4 °C. The antibodies used for immunoblotting included a rabbit anti-TDP-43  polyclonal antibody  and a mouse anti-GAPDH monoclonal antibody (MBL). HRP-conjugated secondary antibodies (Dako) were used. The bands were detected using Immobilon Western Chemiluminescent HRP Substrate (Millipore) and quantitatively analyzed using Amersham Imager 680 .The frozen motor cortex remaining after the DNA methylation analysis was homogenized in 10 volumes of ice-cold RIPA buffer  supplemented with a protease-inhibitor cocktail (Sigma). After sonication on ice , 400 μl of lysates were centrifuged at 100,000 × p < 0.05.For each experiment, the corresponding statistical test, which was two-tailed, is indicated in each figure legend. The number of samples per group is indicated in each figure legend. Statistical significance was considered to exist at Further information on research design is available in the Peer Review FileSupplementary informationDescription of Additional Supplementary FilesSupplementary Data 1Reporting Summary


In full-thickness (FT) wounds, autologous skin cell suspension (ASCS) is used in combination with widely meshed split-thickness skin grafts (mSTSGs) to obtain definitive closure, reducing donor skin requirements compared to traditional autografting (AG) techniques. In the treatment of these wounds, dermal matrices (DMs) are also often utilized to address various challenges including need for temporization, mitigation of contour defects, covering avascular structures, and modulation of scar formation. Varying DMs exist and are composed of different biologic and synthetic materials designed to address these clinical needs. The purpose of this study was to compare outcomes obtained in FT wounds using 3 different DMs coupled with ASCS+mSTSG in immediate or delayed AG procedures.A FT excisional porcine wound model was used. DMs evaluated included a single-layer dermal matrix composed of bovine dermal collagen and elastin (Col/E), a bilayer construct composed of a bovine collagen-glycosaminoglycan with a silicone epidermal layer (Col/GAG), and a synthetic bilayer polyurethane DM (Poly/U).DMs were applied, managed, and grafted following manufacturer’s recommendations. AG included ASCS+mSTSG . Wounds were evaluated for inflammation, infection, DM take, AG take, re-epithelialization, and contracture over 49 days post-excision. Additionally, biopsies were evaluated to further inform tissue generation and healing outcomes.Results related to healing outcomes are reported in the table below. Inflammation at wound margins was noted during acute phase of healing for all DMs and visual cues for infection were noted in 1 wound for Col/E, 3 wounds for Col/GAG causing partial loss of DM, and 1 wound for Poly/U. All signs of infection were resolved by day 14.ASCS+mSTSG can be used successfully over DMs composed of various materials in both immediate and delayed AG procedures. No difference was observed on percent AG take between the DMs, however the data suggest that time to definitive closure is impacted based on utilized DM and AG strategy, with potential implications on contracture.


With the increasing importance of the internet to our everyday lives, questions are rightly being asked about how its' use affects our wellbeing. It is important to be able to effectively measure the effects of the online context, as it allows us to assess the impact of specific online contexts on wellbeing that may not apply to offline wellbeing. This paper describes a scoping review of English language, peer-reviewed articles published in MEDLINE, EMBASE, and PsychInfo between 1st January 2015 and 31st December 2019 to identify what measures are used to assess subjective wellbeing and in particular to identify any measures used in the online context. Two hundred forty studies were identified; 160 studies were removed by abstract screening, and 17 studies were removed by full-text screening, leaving 63 included studies. Fifty-six subjective wellbeing scales were identified with 18 excluded and 38 included for further analysis. Only one study was identified researching online wellbeing, and no specific online wellbeing scale was found. Therefore, common features of the existing scales, such as the number and type of questions, are compared to offer recommendations for building an online wellbeing scale. Such a scale is recommended to be between 3 and 20 questions, using mainly 5-point Likert or Likert-like scales to measure at least positive and negative affect, and ideally life satisfaction, and to use mainly subjective evaluation. Further research is needed to establish how these findings for the offline world effectively translate into an online measure of wellbeing. A single, standardized definition of wellbeing does not currently exist in the literature. Previous attempts to define wellbeing could be argued to be a “description,” rather than a “definition,” as they focus on the dimensions of wellbeing rather than wellbeing itself  is a cognitive-judgmental process  that reviews evidence on the science of happiness and wellbeing and ranks countries by how “happy” they are   reports that 99% of 16–44 year olds in the UK were recent internet users at the time of survey, and only 7.5% of adults in the UK have never used the internet in 2019  and well?being].ti.Titles only were searched because it was felt that it was more likely that this would focus the search on studies that were specifically looking at scales. Words describing the type of wellbeing  were not included as some studies refer to SWB as simply “wellbeing,” leading to potentially missed studies. The term “happiness” was also excluded, as it is often a vague term with multiple meanings  , studies were not appraised for quality, and one researcher performed the analysis. These are discussed in greater detail in The following sections report common features of all the included scales, including how scales are structured, what components of SWB they measure, and how they measure it. Percentages on some tables may not add up to 100% because some scales can be counted under multiple categories. See Additional Material for (1) full list of included and excluded scales and (2) validation and evaluation status of included scales.The mean number of questions was 13 (median 10), with a minimum of 1 and a maximum of 37. Most of the 38 scales (57.9%) had up to 10 questions, and only 18.4% had more than 20 questions. The vast majority of scales used Likert or Likert-like measures (92.1%), with that being the only type of question used for most (86.8%); one also used interviews, and one used Likert, Yes/No, and multiple-choice questions. Only one measure used only multiple-choice questions and one only Yes/No questions, while one had variable question types depending on researchers choices, using the Experience Sampling Method (ESM) ; 55.3% used only these measures in their scale  , this will push the boundaries of what “the online world” is. Moreover, with the arrival of 5G mobile technology, it is expected to further increase consumer demand for online content and services Ofcom, . This siIf questions are not adapted or reworded to fit the online context, it is not guaranteed that online wellbeing is measured. Rewording questions [for example, from “I have been feeling interested in other people”   are underrepresented is unclear, but it may be speculated that Likert-type scale questions offer the ideal mix of characteristics. Yes/No questions suffer from a limited range of responses and does not determine how much respondents agree or disagree with a statement. Multiple choice offers more freedom, depending on the context of the question. Descriptive questions make mass administration of the scale difficult, as a lack of standardization means that each response will need to be analyzed; this is challenging for quantitative analysis, although it provides rich qualitative data in small samples.In terms of the number of points on a Likert scale, measures ranged from 3 to 11. A higher number of options for participants to most accurately represent how they feel may be particularly useful for tracking changes in online wellbeing over time, capturing smaller increases or decreases in mood: an increase from three to four on a 5-point scale is a greater increase than three to four on a 10-point scale, so respondents may be more likely to stick to the lower number. On the other hand, longer scale items may provide too much choice or take longer for respondents to complete, leading to less consistency between answers measuring the same thing: if four or five are seen as very close together, the choice between them may be random and differences missed. “The Paradox of Choice” also argues that excessive choice increases difficulty in choosing an option and decreases satisfaction with the choice , and in general, people may be more receptive to “rises in wellbeing” than reporting increases in poor wellbeing. This would suggest that an OWS might be better scored positively; however, in some contexts, this might not make sense. For example, if a questionnaire is asking how often something has occurred, for example, feeling happy or sad, it might be more intuitive for higher scores to equal more often, whether or not the statement was positive. For scales that measure several components of SWB (see next section), having more often high scores for positive items and low for negative items would be confusing. This leads to discussion of the possibility of reverse scoring. The majority of scales did not use reverse scoring. Equal numbers of scales used reverse scoring for only positive or only negative affect items. If positive scoring is used, negative affect questions can be reverse scored; otherwise, a high negative affect score would be taken to mean good wellbeing. There is a theoretical risk that including a high number of reverse-scored questions could increase the complexity; having a mix of positive and negative statements may also cause mistakes from misreading. This has been demonstrated in  (Larson and Csikszentmihalyi, The vast majority of scales measured wellbeing by directly asking for a subjective evaluation from respondents, with some of these using additional alternative measures. Very few scales only rely on alternative measures; an example is the laughter frequency scale (Murakami et al., However, the notion that objective indicators are not useful and do not correlate to SWB is not true (Oswald and Wu, how much social interaction do you receive?,” a potentially better question to ask is, “do you receive enough social interaction to satisfy you?.” The advantage of the latter is that it accommodates for people who prefer not to interact much with others, and the question asks respondents to compare what they currently have relative to their ideal.Alternative measures should also be phrased in a way that accommodates for different individual ideals. For example, instead of asking “The search for wellbeing scales was intended to be comprehensive but focused, but some literature will be missed, and therefore, there are SWB scales that are not included. To consider more wellbeing scales is outside of this review's aims but is certainly an area for further exploration. Far more wellbeing scales exist, and reading is available such as Boyle et al. . AnotherStudies were not appraised for quality, in favor of identifying as many scales as possible and not looking into the research carried out with them. Some scales reviewed may be low quality or biased, which could in turn bias the results and conclusion of this paper. However, the vast majority of the scales had some form of validation reported, and only three of the scales were produced solely for the purpose of a single study. Additionally, many of the recommendations were made based on several scales, including many that are strongly validated in previous research. This study was also not designed to determine the reasoning behind design choices in SWB scales, focusing on observing trends in current scales instead. Scoping reviews are intended to be a narrative overview of the literature (Arksey and O'Malley, Another limitation is that without a standardized definition of SBW, it can be problematic to recommend existing SWB measurements to the development of a new OWB assessment tool, especially when assuming that the psychometric qualities transferred from SBW to OWB remain the same. This is a limitation that should be kept in mind when applying the recommendations derived from this scoping review.Finally, one researcher performed the analysis using agreed definitions for terms related to SWB, which could lead to mistakes or biased judgments. However, topic experts were able to agree on stringently defined terms before analysis took place, so it is hoped that another researcher using the same definitions would arrive at similar results. Regardless, multiple researchers analyzing data independently are still preferred.This paper describes a broad scoping review of existing measures of SWB, highlighting the lack of online wellbeing measurement research, and compiling features of existing scales to offer recommendations for an OWS. Online wellbeing should be distinguished from generalized SWB, with an OWS focusing on areas of wellbeing that are contextually important to the online world. To summarize, an OWS is recommended to be between 3 and 20 questions and consider developing a brief measure if longer; use mainly 5-point Likert or Likert-like scales, with predominantly positive scoring, using reverse scoring if negative affect is to be measured alongside other SWB components; measure at least positive and negative affect and ideally life satisfaction; ask for evaluations within 1–2 weeks and a month at the maximum; and use mainly subjective evaluations with alternative measures being used as supporting questions if needed.The search and proposed recommendations for building an OWS are based on how current SWB scales are used in research. By focusing on field-tested SWB scales, the paper examined what is used in practice instead of what works in theory. It needs to be stressed that there is much research to be done to test these recommendations, especially in assessing the accepted components of SWB and how the online world might be unique. Most critically, a clear, accepted definition of the “online world” and what it means in relation to online wellbeing needs to be developed for research into online wellbeing to fruitfully continue. We welcome future work that incorporates the recommendations from this paper to develop and validate a new measure for OWS alongside existing SWB measures to test the assumptions surrounding what effects a persons' online wellbeing.ZO carried out the data collection and analysis and drafted the first version of the paper. LD edited and formatted all drafts of the paper. EP acted as main supervisor for the study, with LD, MR, and YL providing advice at various stages. EP, MR, and YL also commented on versions of the paper and approved the final manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Elder abuse and neglect (EAN) comprises multiple dimensions, is experienced by about 10% of older adults in the U.S in diverse communities, and is severely detrimental to older adults’ (OA) health and wellbeing. However, documentation of EAN among refugee OA is greatly lacking as are services for these communities. Refugee OA are overall underserved members of marginalized communities. This paper reports on a community-engaged study to collect information and raise awareness of EAN among OA in 2 North Carolina refugee communities - Nepali-speaking Bhutanese and Congolese. Research partners included University researchers and community refugee-serving organizations. Surveys and focus group interviews were conducted. 17 Nepali-speaking Bhutanese and 13 Congolese filled out survey questions, including the Elder Abuse Suspicion Index. They participated in focus group discussions (FGDs), separately for men and women of each community. Survey results indicated EAN more among Congolese than Nepali-speaking Bhutanese. FGD results showed both communities prefer to depend on family members, and experience difficulties with language, transportation, and economic insecurity. No EAN was reported in the FGDs. In line with principles of community-engaged approaches, a capacity-building event to increase awareness of EAN was held, attended by 25 persons from the two communities. This study adds documentation on an under-researched area and marginalized communities. Action recommendations include disseminating culturally appropriate EAN information, strengthening English language and job skills and transportation options, encouraging cooperation across state, nonprofit, educational, and service organizations to address needs of older refugee adults.


Sarcoidosis is a disease with an unknown cause that affects multiple organ systems and has a varied clinical presentation. Often, its symptomatology mimics other disease processes, such as lymphoma, tuberculosis, and amyloidosis. The reticuloendothelial involvement and typical B symptoms of weight loss, fatigue, night sweats, and lymphadenopathy can make sarcoidosis often easily confused with lymphoma. Sarcoidosis has a myriad of central nervous system (CNS) effects, which are often not recognized as symptoms of the disease. These neuropsychiatric symptoms can include, but are not limited to, cognitive decline, headaches, and personality changes. In this report, we discuss a case of a patient who presented with symptoms consistent with indolent lymphoma but was eventually diagnosed with sarcoidosis with extrapulmonary manifestations. Sarcoidosis is a systemic disease process that has a varied clinical presentation. The primary manifestation of the disease is pulmonary, with 95% of patients presenting with evidence of pulmonary sarcoidosis. However, many organ systems can be involved, including the eyes, skin, lymphatics, liver, kidneys, central nervous system (CNS), and spleen. More than 40% of patients have extrapulmonary manifestations at the time of presentation. CNS involvement occurs in about 5% of patients . BecauseWhile the underlying cause of sarcoidosis is not well understood, the immune system plays a central role in its pathogenesis. Noncaseating granulomas are seen histologically, which are also associated with other pathologies such as malignancy, infection , and occupational and environmental exposures (such as beryllium or silica) . It is iIn this case report, we present a case of sarcoidosis with initial findings suggestive of indolent lymphoma. Further history gathering and workup resulted in a diagnosis of sarcoidosis with extrapulmonary manifestations. The clinical picture was further complicated by unexplained recent cognitive decline, prompting a concomitant neurologic workup. The cognitive dysfunction was ultimately felt to be associated with sarcoidosis, with consideration given to neurosarcoidosis (NS) versus sequelae of the sarcoidosis “penumbra.” In addition to highlighting the challenges in distinguishing sarcoidosis from an indolent lymphoma, we also focus on the importance of under-recognized neuropsychiatric effects of sarcoidosis.A 65-year-old African American male with a history of chronic obstructive pulmonary disease (COPD), anemia, and heart failure with preserved ejection fraction (HFpEF) presented to the emergency department with complaints of unintentional weight loss, fevers, chills, and memory decline. He had lost 60 pounds within the past year, with associated functional decline and generalized fatigue. Within the past two months, he had developed fevers and night sweats, and within the past week, he had begun to experience cognitive decline described as being in a “fog,” which had led him to miss familiar exits on the highway and forget his way to his doctor’s office.2 saturation of 97%, and temperature of 98.3 °F. Physical exam showed a thin-appearing man in moderate distress secondary to shortness of breath and cognitive issues. Pertinent positives included bilateral shoddy cervical lymphadenopathy, increased respiratory effort with bilateral wheezing and inspiratory crackles, 1+ pretibial edema, and large bilateral axillary lymphadenopathy. A mini-mental status exam (MMSE) revealed a score of 24/30. Laboratory workup revealed WBC of 10.1 x 1000/mm3, Hemoglobin (Hb) of 9.5 g/dL, and platelet count of 400 x 1000/mm3. The basic metabolic panel (BMP) showed sodium of 130 mmol/L, potassium of 3.3 mEq/L, and creatinine of 0.84 mg/dL. Brain natriuretic peptide (BNP) was 225 pg/mL . A chest X-ray showed cardiomegaly and mild interstitial edema with bilateral pleural effusions. CT brain revealed no acute findings. Given the patient’s functional decline, diffuse lymphadenopathy, and worsening mental status, he was admitted for further workup and management.Upon presentation to the emergency department, his vitals included a blood pressure of 117/51 mmHg, heart rate of 95 beats per minute, respiratory rate of 18 breaths per minute, OOn day two of his admission, collateral information was obtained from the patient’s family, which revealed additional prior workup for his symptoms. Six months beforehand, the patient had been evaluated for worsening blurred vision and had been diagnosed with bilateral panuveitis. An extensive laboratory workup was performed, which is summarized below in Table Extensive radiology and pathology workup was performed and raised concerns for sarcoidosis. Although the patient had been prescribed methotrexate (MTX), he reported never starting it. One month prior to presentation, the patient had undergone a CT of the chest, abdomen, and pelvis with contrast, which had revealed multiple enlarged mediastinal and axillary lymph nodes and extensive bronchiectasis of bilateral lungs, with the lymphadenopathy (LAD) considered to be reactive versus neoplastic Figure .Given this new information, rheumatology was consulted, inflammatory markers were drawn which showed an elevated C-reactive protein (CRP) of 50.4 mg/L , and an erythrocyte sedimentation rate (ESR) of 97 mm/hr ; an excisional lymph node biopsy was pursued. Pathology from the axillary lymph node biopsy  reported two similar cases of one-year histories of fatigue, fever, shortness of breath, and night sweats whose initial biopsies were consistent with sarcoidosis, but were ultimately found to have Hodgkin’s lymphoma . A seconIn this case, the patient’s concurrent cognitive decline complicated his workup and management. Initially, the differential diagnosis for his cognitive decline included NS, meningoencephalitis, toxic-metabolic encephalopathy, tuberculous meningitis, CNS fungal infection, and dementia (Alzheimer’s versus vascular). Prior laboratory workup ruled out other causes such as neurosyphilis, HIV, herpes simplex virus (HSV), toxoplasmosis, and anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. Given the negative MRI, clinical improvement, and biopsy-proven sarcoidosis, the differential diagnosis was narrowed, with particular focus on NS without signs of active inflammation versus parasarcoidosis, an under-reported entity. Improvement of mental status over the course of hospitalization was likely multifactorial after treatment with prednisone and MTX for sarcoidosis, fever reduction with acetaminophen, and improved nutrition.Neurologic complaints are reported in 5-15% of all patients with sarcoidosis . The diaOur patient partially met the criteria for a “probable” diagnosis of NS, given there was evidence of extra-neural sarcoidosis but with negative MRI findings. Although MRI is considered to be the most sensitive (82-97%) imaging study for NS, a study in the Quarterly Journal of Medicine highlights its imperfect nature, in that six of 54 NS cases (11%) had normal MRI findings . CerebroAn alternative explanation considered for our patient’s cognitive decline was parasarcoidosis, or the “sarcoidosis penumbra.” The most prevalent symptoms of parasarcoidosis include fatigue (70-80%), small-fiber neuropathy (30%), and cognitive impairment (35%). Included sequelae are “cognitive difficulties, such as impaired memory, slowed thinking, and diminished attention and concentration,” all in the setting of “no discernible evidence of nervous system inflammation" .Even though parasarcoidosis affects over 50% of sarcoidosis patients, there is a lack of available literature on its management. One study has suggested that its pathogenesis is related to a systemic increase in tumor necrosis factor-α (TNF-α), a cytokine seen in inflammatory states that directly impacts neurotransmitter metabolism and synaptic transmission. This same study showed an improvement in cognition with anti-TNF-α medications, while patients who were treated with steroids +/- MTX did not show any improvement, further supporting the theorized mechanism of parasarcoidosis.As seen in this study, sarcoidosis and lymphoma can present with similar systemic manifestations, with the ultimate diagnosis usually confirmed by biopsy. Although other studies have demonstrated a similar diagnostic dilemma, our patient's case was further complicated by his cognitive decline. Given a lack of active NS findings on MRI, a diagnosis of parasarcoidoiss was considered. Additional studies are needed to help elucidate both a diagnostic criterion for parasarcoidosis and measures for its optimal management.Sarcoidosis is a chronic granulomatous disease of unknown cause that presents with highly variable symptoms, especially when patients demonstrate extrapulmonary manifestations. The typical B symptoms of fatigue, weight loss, night sweats, and lymphadenopathy observed in sarcoidosis are often confused with lymphoma and other malignancies. These must be distinguished from lymphoma with histologic evidence of noncaseating granulomas. Other fungal, bacterial, and viral pathologies should also be excluded. While the JAMA Neurology guidelines published in 2018 improved the diagnostic schema for NS diagnosis, our case highlights the continued ambiguity in distinguishing NS from parasarcoidosis. Cognitive decline is an under-recognized but important symptom of sarcoidosis, especially given the expected improvement with appropriate therapeutics. Further investigation is warranted to help determine more specific testing methods for parasarcoidosis. Additionally, while TNF-α agents have been shown to be promising therapeutic agents for the sarcoidosis penumbra, more research is needed to properly determine the mechanism of parasarcoidosis in order to help guide future therapy.


Since its discovery in 2004, graphene has attracted worldwide attention due to its excellent physical and chemical properties. Herein, this review summarizes the latest developments in graphene frameworks, heteroatom-modified graphene, and graphene composite frameworks in sulfur cathodes. Moreover, the challenges and future development of graphene-based sulfur cathodes are also discussed.The global energy crisis and environmental problems are becoming increasingly serious. It is now urgent to vigorously develop an efficient energy storage system. Lithium-sulfur batteries (LSBs) are considered to be one of the most promising candidates for next-generation energy storage systems due to their high energy density. Sulfur is abundant on Earth, low-cost, and environmentally friendly, which is consistent with the characteristics of new clean energy. Although LSBs possess numerous advantages, they still suffer from numerous problems such as the dissolution and diffusion of sulfur intermediate products during the discharge process, the expansion of the electrode volume, and so on, which severely limit their further development. Graphene is a two-dimensional crystal material with a single atomic layer thickness and honeycomb bonding structure formed by sp Facing the depletion of fossil fuels and gradual serious environmental pollution problems, people have slowly realized the necessity of clean energy development. Sustainable energy such as solar and wind energy has been extensively developed . However−1 and a theoretical energy density of 2600 Wh·kg−1 . B. B35]. Bne plane ,37. IntrIn recent years, a variety of graphene/sulfur configuration materials have been developed as sulfur cathodes. In order to maximize the utilization of active materials, researchers have studied the graphene/sulfur configuration from a variety of perspectives. The basic configuration is divided into the following types: in-plane, three-dimensional sandwich, three-dimensional core-shell, and so on. This section summarizes the various configurations of sulfur cathodes based on unmodified graphene.There are several forms for in-plane: graphene sheets, graphene paper, graphene nanoribbons, etc. ,42,43,44−1 at 0.1 C was also due to the effective physical limitation of the sandwich structure. Fang et al. prepared a full graphene sandwich structure composed of high-porosity graphene (HPG), highly conductive graphene (HCG), and partial graphene oxide (POG)  a [48]. S0 cycles d. There 0 cycles b. This sThe core-shell structure has been proven to be able to solve the above-mentioned problems of LiPS leakage and poor volume buffer capacity. Graphene is used as an outer packaging to firmly bind the sulfur particles in the shell e,h. The + with polysulfides. The oxygen-containing groups and a large amount of space in the rGO aerogel inhibit the migration of LiPSs from the cathode . . 2 is alr method , and fin3S2) has also received attention in supercapacitors. Ni3S2 is not only low-cost but is also highly conductive. Guo et al. synthesized a Ni3S2/-rGO hybrid material , , 141], g−2 had a better specific capacity when doped with 2 wt% CNT .The amount and form of loading sulfur are also some of the evaluation criteria for electrode performance. For GO/CNT/S prepared by the freeze-drying method, Hwa first added sulfur and its sulfides during the electrode preparation process and finally removed the impurities , while G3 in the electrolyte. Lee et al. prepared a graphene-loaded N-doped carbon framework (NCF-G) [−1. Sun et al. decorated graphene with N and S co-doped carbon nanowalls (NSCNWs) to effectively trap polysulfides [The abundant functional groups on graphene are also one of the breakthrough points of G/CNT composites. Combined with the heteroatom-modified graphene structure mentioned in previous sections, single-atom doping or diatomic co-doping are both effective ways to improve the adsorption performance of G/CNT. For example, Su et al. converted Prussian blue (dehydrated sodium ferrocyanide) into a N-doped graphene-carbon nanotube hybrid material through one-step pyrolysis . The act (NCF-G) . The inisulfides . The NSC+. The most important thing is that it can fix polysulfides well. Zhou et al. designed N-doped double-shelled hollow carbon spheres (G–NDHCS–S) coated with graphene to capture sulfur [−1 at a current rate of 0.2 C. The graphene/carbon nanosphere composite material synthesized by Jia et al. possessed a specific surface area of 3200 m2·g−1 [−1 after 100 cycles. Therefore, the potential performance of the spherical structure electrode in the LSBs has a very broad development prospect.In addition to the CNT structure, electrodes with spherical structures have also been studied accordingly. The nanosphere structure can hold a large amount of sulfur and increase the contact area with the electrolyte to promote the transport of Lie sulfur . Due to 0 m2·g−1 . Its strAdditionally, current collectors based on other carbon materials and graphene have shown multiple advantages in LSBs. First, they show excellent flexibility. This is particularly prominent in CNT/graphene electrodes and provides an important foundation for the research of flexible batteries. Second, they mostly act as porous containers to hold polysulfides during the oxidation–reduction reaction process and improve the cycle stability of the battery.In summary, this article took graphene as a theme and summarized the potential applications of the pure graphene framework, heteroatom-modified graphene framework, and graphene composite framework in LSB cathodes in detail, aiming at obtaining LSBs with high energy density and long cycle capability and promoting their long-term development and application. The idea of graphene as a sulfur cathode carrier originates from its high conductivity, large specific surface area, and strong adsorption capacity for LiPSs on a surface defect. This viewpoint has also been confirmed by the composite structure of sulfur and the simple graphene framework. Sulfur cathodes have been designed with various structures such as sandwich, core-shell, and hybrid structures. Due to the flexibility and controllable assembly capabilities of graphene, the electrochemical performance of LSBs has improved rapidly. In the field of heteroatom-modified graphene cathodes, researchers gradually discovered that pyridinic-N had stronger chemisorption energy than other forms. It is worth noting that in addition to chemical bonding, transition metal doping also exhibits additional electrocatalytic capabilities. In order to solve the problem of limited content of single atom doping, researchers have gradually used diatomic doped graphene to achieve the common capture of LiPSs by a variety of chemical bonds. Metal compound additives have two main functions in the S electrode: one is to fix polysulfides, and the other is to catalyze redox reactions to promote polysulfide conversion. A small number of metal compounds can also serve as active materials to store lithium, increasing the lithium storage capacity. The advantage of the composite of other carbon materials and graphene is to achieve a diversified conductive network structure, thereby improving the conductivity of the skeleton, increasing the sulfur content and expanding the pore volume.However, although many efforts have been made to achieve better electrochemical performance, there are still many new challenges in LiSBs. For instance, although the stronger bonding force of pyridinic-N has been confirmed through repeated experiments, accurate control of the type and content of nitrogen doping cannot be achieved. The cost of boron doping is high, the doping process is complex, and the accuracy of characterization is difficult. The theoretical system for the interaction of transition metals and graphene bonds is not yet clear. There are also many challenges in the field of heteroatom doping. For metal additives, although catalytic conversion and effective chemical bonding inhibit the diffusion of polysulfides, the conductivity of such additives is not ideal, which inevitably reduces the battery capacity and cycle capacity. In this respect, the conversion of the catalyst into quantum dots may produce unexpected performance results.For graphene substrate materials, the key to improve the electrochemical performance of LSBs is the dissolution of polysulfides. The inhibiting of polysulfide diffusion has mainly focused on the physical properties of macroscopic physical encapsulation and microscopic van der Waals forces. In terms of chemical properties, it has the function of chemical bonding and catalysis, which accelerates the reaction process. The combination of physical action and chemical action is expected to be the most effective way of inhibition. This is a long way toward the industrial production of lithium-sulfur batteries, and it is necessary to coordinate development in many aspects such as the preparation process, applicable environment, high energy density, and economic benefits to promote the commercial application of LSBs.