The neuronal cell adhesion and recognition molecule L1 does not only ‘keep cells together’ by way of homophilic and heterophilic interactions, but can also promote cell motility when cleaved into fragments by several proteases. It has largely been thought that such fragments are signs of degradation. Now, it is clear that proteolysis contributes to the pronounced functional diversity of L1, which we have reviewed in this work. L1 fragments generated at the plasma membrane are released into the extracellular space, whereas other membrane-bound fragments are internalised and enter the nucleus, thus conveying extracellular signals to the cell interior. Post-translational modifications on L1 determine the sequence of cleavage by proteases and the subcellular localisation of the generated fragments. Inside the neuronal cells, L1 fragments interact with various binding partners to facilitate morphogenic events, as well as regenerative processes. The stimulation of L1 proteolysis via injection of L1 peptides or proteases active on L1 or L1 mimetics is a promising tool for therapy of injured nervous systems. The collective findings gathered over the years not only shed light on the great functional diversity of L1 and its fragments, but also provide novel mechanistic insights into the adhesion molecule proteolysis that is active in the developing and diseased nervous system. Neural cell adhesion molecules, also called cell recognition molecules, belong to an integral membrane protein superfamily with characteristic adhesive and signalling properties . In partL1 has been described as a cell recognition molecule , which fThe protein backbone of L1 consists of a short and highly conserved cytoplasmic domain, a transmembrane part, and an extracellular region formed by six immunoglobulin (Ig)-like and five fibronectin-type III (FNIII)-like domains , as showInitially, L1 was found in the nervous system, and has been thoroughly studied. However, the molecule has been also detected in different types of cancer . In patiSeveral proteases are involved in the process of the ectodomain shedding of L1 B; these X [X is involved in the processing of L1 by proteases, and myelin basic protein (MBP) was identified as a serine protease for L1, which interacts with L1 in a LewisX-dependent manner [Shiverer mice, which are deficient in MBP, show a progressive disorder characterised by tremors and seizures, leading to early death [shiverer mice) or the mutagenesis of the proteolytically active or cleavage sites, as well as by the application of serine protease inhibitors. The MBP-mediated generation of L1-70 promotes neurite outgrowth and the survival of neurons, as shown in vitro. Interestingly, in dissociated cerebellar neurons from wild-type and MBP-deficient shiverer mice, and when cultured in a medium supplemented with the MBP antibody or L1 holding the MBP cleavage site, the formation of neurites and neuronal survival is hampered [X-based interaction between L1 and MBP in the nervous system [L1 carries the carbohydrate LewisX , which iX . LewisX t manner ,68. MBP t manner ,71,72,73ly death ,74. Surply death . After tly death ,68. MBP hampered ,68. The s system ,68.shiverer embryos in utero prevented the manifestation of all the developmental spinal cord abnormalities mentioned above. However, these parameters become abnormal after the in utero injection of proteolytically inactive MBP. These findings suggest that the serine protease MBP acts on L1 to facilitate important morphogenic events during the early stages of nervous system development [Further studies on the relevance of the proteolytic activity of MBP on L1 in vivo, in the developing spinal cord, have identified the proteolytically active site in MBP . A serinelopment .In addition to its essential role in the formation of the nervous system, L1 also stimulates recovery processes in animal models of acute and chronic neurodegenerative entities . Does th858RKHSKR863) and the appearance of an 80 kDa fragment (L1-80), and stimulate the migration and axonal outgrowth of dissociated cortical and cerebellar neurons [reeler) mice invade the marginal zone, unlike the cells of the wild-type mice. It is therefore worth mentioning that the developing L1-deficient cerebral cortex displays morphological abnormalities in layer formation, partially overlapping with those seen in the cerebral cortices of the reeler mice. However, in utero electroporetic administration of L1-80 into the cortices of reeler embryos normalises neuronal migration [In the search for other early proteases/binding partners that target L1, the extracellular matrix protein Reelin has been identified as interacting with cell adhesion molecule L1 . Reelin  neurons . Remarka neurons . On the  neurons , since tigration . These figration . Thus, tIn this respect, it is important to mention that another member of the CAM family, the neural cell adhesion molecule NCAM, is prone to proteolysis in a similar fashion to L1. NCAM is crucial not only for the proper development of the nervous system, but also for maintaining the high cognitive functions of the adult brain . Simila1 activates the cleavage of L1 by a serine protease at the plasmalemma. This yields a sumoylated transmembrane L1 part of approximately 70 kDa  by cathepsin E . L1-30 e1172, or the cathepsin E cleavage site at E1167, eradicates the formation of L1-30, whereas alteration of the nuclear localisation signal at K1147 averts the nuclear internalisation of the fragment, but not its generation. Additionally, L1-30 production can be blocked by pepstatin, an aspartyl protease inhibitor, which also inhibits the L1-induced migration of cerebellar neurons and Schwann cells in dorsal root ganglia, thus impairing axonal myelination [Modification of the sumoylation site at Klination . Howeverlination ,112. Mutlination . These oWhen serine proteases and cathepsin E cleave L1 at the plasma membrane, another membrane-bound fragment of approximately 55 kDa (L1-55) is generated : see FigInterestingly, the post-translational modification of L1 may determine which fragments can be proteolytically generated ,110. In 1136LILL) in the transmembrane domain and one FXXLF motif (F1046HILF) in the fifth FNIII-like sequence of L1. L1136LILL is also present in the co-regulators (co-activators and co-repressors) of nuclear receptors, which are DNA-binding transcription factors essential for the development, differentiation, and metabolism of the eukaryotic cells [The nuclear presence of L1 fragments implies possible interactions with other molecules. In the search for motifs in L1 that are known to mediate possible interactions between L1 and nuclear molecules, Kraus et al.  identifiic cells ,126,127.ic cells ,131,132.ic cells . AlteratRecently, a new potential binding partner of the intracellular L1 domain has been identified (included into the previously mentioned fragment L1-55) . L1-55 bAll these observations raise the question of whether the cleavage and nuclear translocation of fragments can be seen also for other L1 family members. Notably, NCAM is proteolytically cleaved by matrix metalloproteases at the plasma membrane ,148. WheAnother provocative question is whether the third FNIII-like domain of L1, which is a target of many proteases, can be used as a potential therapeutic stimulator of L1-specific functions. To answer this question, Schulz et al.  used a 2Kataria et al.  identifiExperimental evidence gathered in recent years sheds light on the great functional diversity of L1 and its fragments that emerge in the process of proteolysis. L1 not only mediates adhesion between cells, but can also promote cell motility when cleaved into fragments by several proteases. Now, it is clear that proteolysis is not a sign of degradation; rather, it contributes to the functional heterogeneity of L1, together with distinct post-translational modifications of the cleaved fragments. Carbohydrates attached to the protein backbone and co-entering the cell nucleus contribute to specific functions of the carrier molecule/fragment. Moreover, carbohydrates can affect sumoylation and the intracellular fate of proteolytic fragments, and shape morphogenic events that are required not only for proper development but also for the regeneration of the nervous system. Taken together, these data indicate that targeting the proteolysis of cell adhesion molecules is a promising tool for therapy of the acute or chronically injured nervous system.


Sarcoidosis is an enigma diagnosed by ruling out other etiologies of granulomatous inflammation. The multisystem manifestations of sarcoidosis and the clinical polymorphism pose a diagnostic challenge to all physicians. The skin is the most commonly affected organ after the lungs in sarcoidosis. Dermatological manifestations can appear before, during, or after systemic involvement, and the type of skin lesion can have prognostic significance. Also, a biopsy of skin lesions is less invasive and more accessible to perform than a biopsy of visceral organs. Thus, in certain ways, cutaneous manifestations can aid in the diagnosis and prognosis of systemic disease. This article has focused on the frequently encountered skin lesions of sarcoidosis along with their prevalence, clinical features, and management. Sarcoidosis is a multisystemic disease that affects people from all over the world. It is characterized by the presence of non-caseating granulomas in the involved organs. Granulomas can be found in any organ, but the lungs are the most common organs involved with bilateral hilar lymphadenopathy .Jonathan Hutchinson described the first case of sarcoidosis in 1875 when it was more of a dermatological curiosity. However, as science progressed and more research was conducted, the disease gradually evolved into a multisystemic one ,3. GlobaSarcoidosis has a variety of clinical symptoms, but virtually all patients experience respiratory tract involvement at some point. The most common symptoms are dry cough, dyspnea, and chest discomfort, particularly in patients with severe endobronchial or parenchymal involvement . The nexThe underlying mechanism of sarcoidosis is believed to be a link between genetic susceptibility and environmental or infectious factors. Additional research is needed to determine the exact cause of sarcoidosis, how granulomas form, and the various skin lesions that sarcoidosis can cause such as erythema nodosum and LP, maculopapular, nodular, and annular lesions. Skin sarcoidosis affects roughly 25% of people with systemic illness and may also arise in isolation . A varieCS is known as the great imitator because of its wide range of morphologies . It is cCutaneous lesions can aid in diagnosing sarcoidosis and are easily accessible tissues for biopsy . It is cCommon dermatological manifestations of sarcoidosis will be discussed in the subsequent text.Papular and plaque sarcoidosisThe most frequently seen variants of CS are papules and plaques. As per a study by Rim Ishak et al. in 2015 on 76 patients from the American University of Beirut Medical Center diagnosed with CS between 1992 and 2010, 37 patients had plaques (49%) and 22 patients had papules (29%) . The finMaculopapules are red-brown to purple, less than 1 cm in diameter, and very weakly infiltrated with some epidermal alteration. They are less commonly skin-colored, yellow-brown, or hypopigmented. The papules have a characteristic translucent yellow-brown tint in the background of erythema. The distinctive apple jelly color of the granulomatous skin lesion is seen on diascopy ,26. An uThey're widely diffused and found predominantly on the face and neck, especially on the eyelids, around the orbits, and in the nasolabial folds, as well as the occipital area of the neck . Recent Papules, notably on the extensor surfaces of arms, face, scalp, back, and buttocks, can progress into plaques greater than 5 mm ,31. ThesSubcutaneous sarcoidosisSubcutaneous sarcoidosis is the least common among the specific lesions of the CS. Its incidence is high in the fourth decade and most common in women than men. Multiple, firm, asymptomatic to slightly painful, mobile, round to oval, skin-colored nodules frequently occur in a bilateral and asymmetric pattern on the extremities . Ahmed eSubcutaneous sarcoidosis typically manifests at the start of the disease, and it usually indicates sarcoidosis with non-severe systemic involvement and is not linked to chronic fibrotic illness. A clinicopathological study by J Marcoval et al. in 2005 revealed that in 85 of 480 patients with systemic sarcoidosis, granulomatous cutaneous involvement was found. Subcutaneous sarcoidosis was diagnosed in 10 of the 85 cases, and in all these 10 cases, subcutaneous nodules appeared at the beginning stage of the disease. None experienced chronic or severe sarcoidosis consequences such as pulmonary fibrosis and bone cysts . DiffereThe need for and the type of treatment depends on the severity of the systemic condition. Systemic corticosteroid therapy is the basis of treatment for patients with significant systemic involvement or disfiguring skin lesions. The therapeutic response of skin lesions to oral corticosteroids was observed in all patients who received corticosteroids as their primary treatment in a series conducted by Ahmed and his colleagues as mentioned above. The daily dosage ranged from 20 to 40 mg, and responses were frequently evident four to eight weeks after treatment began . In rareScar sarcoidosisLesions of CS can also appear in pre-existing scars . A scar Clinically, the lesions present as papules, plaques, nodules, and Ill-defined erythemas. Plaque formation was seen in the scars of eight patients in a study by T Atci and his colleagues . When noExamining the scars of individuals with suspected or confirmed sarcoidosis is significant since a biopsy of these scars can be easily performed, confirming the diagnosis and preventing more invasive examinations . KeloidsLupus pernioLP is the most distinctive cutaneous lesion of sarcoidosis. The exact mechanism of development of LP in cases of sarcoidosis is unknown. It is more commonly seen in women with long-standing sarcoidosis, as evident in the subsequent studies discussed below ,26,45. ALP can be a vigorous disease that obstructs the upper respiratory tract internally and externally, necessitating aggressive therapy . It is aErythema nodosumIt is the most common non-specific cutaneous lesion of sarcoidosis as no granulomas are found on histological examination. Approximately 10-22% of all erythema nodosum cases are caused by sarcoidosis . Its mosIt is an acute marker of sarcoidosis and is believed to be triggered by the undergoing inflammatory process. Inflammation of the subcutaneous fat gives rise to tender, warm subcutaneous nodules that range in color from erythematous to violaceous to brown. It is most commonly observed on the shins . There aTriad of erythema nodosum, bilateral hilar lymphadenopathy on X-ray, and joint symptoms such as arthritis of the ankles, wrists, and elbows make up Lofgren's syndrome, which is highly specific for sarcoidosis . Though Diagnosis and managementTo establish the diagnosis of CS, a biopsy and histopathological examination is required, along with the morphological presentation. Sarcoidosis should be well-considered in the differential diagnosis of various skin lesions . It mustTreatment options are primarily based on circumstantial evidence. Observation without therapy is recommended, as most lesions are asymptomatic and often resolve spontaneously. However, disfiguring and extensive skin lesions associated with severe systemic illness require treatment . TreatmeSmall papules and plaques are often treated effectively with monthly intralesional triamcinolone injections. Treatment with a topical corticosteroid and a hydrocolloid occlusive dressing on a weekly basis can also be useful . ClinicaLimitationsThis review has some limitations. It doesn't include uncommon dermatological manifestations of sarcoidosis like ichthyosiform sarcoidosis, scalp sarcoidosis, atrophic and ulcerative sarcoidosis, mucosal and nail sarcoidosis, and a few of the studies mentioned here are case studies and reports with a very small sample population.Sarcoidosis is a multisystem idiopathic disease that forms noncaseating epithelioid cell tubercles in affected tissues or organs. Understanding the wide range of sarcoidosis clinical manifestations can help avoid diagnostic delays. Skin is the first and most common extrapulmonary manifestation of sarcoidosis. The most common cutaneous manifestations are macules, papules, plaques, subcutaneous nodules, LP, scar sarcoidosis, and erythema nodosum. Maculopapules, subcutaneous nodules, and erythema nodosum are typically associated with acute sarcoidosis. They indicate a favorable prognosis, whereas plaque-type lesions and LP are more commonly associated with advanced stages and necessitate treatment. Regardless of the extent of cutaneous involvement, patients with CS must be closely monitored. Sarcoidosis-related skin eruptions are exceedingly diverse and can resemble a variety of skin illnesses. It's tough to classify CS because many kinds appear to be mixed, and there is no consistently effective treatment. More future studies are required on the diagnosis and management aspects to improve the care of patients with CS.


Bombus terrestris audax (Harris) to explore the detectability of an elevated floral humidity signal when presented against different levels of environmental noise. Artificial flowers were constructed that could be either dry or humid, and individual bumblebees were presented with consistent rewards in either the humid or dry flowers presented in an environment with four levels of constant humidity, ranging from low (~20% RH) to highly saturated (~95% RH). Ability to learn was dependent upon both the rewarding flower type and the environment: the bumblebees were able to learn rewarding dry flowers in all environments, but their ability to learn humid rewarding flowers was dependent on the environmental humidity, and they were unable to learn humid rewarding flowers when the environment was highly saturated. This suggests that floral humidity might be masked from bumblebees in humid environments, suggesting that it may be a more useful signal to insect pollinators in arid environments.Flowers produce local humidity that is often greater than that of the surrounding environment, and studies have shown that insect pollinators may be able to use this humidity difference to locate and identify suitable flowers. However, environmental humidity is highly heterogeneous, and is likely to affect the detectability of floral humidity, potentially constraining the contexts in which it can be used as a salient communication pathway between plants and their pollinators. In this study, we use differential conditioning techniques on bumblebees  Nicotiana tabacum L. [Solanales: Solanaceae]) but reached up to 3.71%  Griseb. [Solanales: Convolvulaceae]).Most plant-pollinator interactions involve the plant producing signals that manipulate the pollinator to bring it to the plant. These signals can work across many different sensory modalities, and may include color , shape aHyles lineata Fabricius (Lepidoptera: Sphingidae) was demonstrated  , and the bumblebee Bombus terrestris (L.) (Hymenoptera: Apidae) is capable of learning and differentiating between artificial flowers that mimic natural humidity patterns  against different levels of signaling noise comparable with native conditions. This species is suitable for these experiments, as B. terrestris foragers have been used in similar differential conditioning experiments to those described here, showing a capacity to detect floral humidity and associate nectar with both humid and dry artificial flowers  were housed in an internal laboratory maintained at 21°C and 40 ± 5% RH (relative humidity), under an array of overhead fluorescent lights  programmed to provide a 12-hr day–night cycle. The nestboxes were connected to separate 72 cm × 104 cm × 30 cm flight arenas by gated tunnels where access could be controlled by the experimenter. The floor of each arena was covered with a layer of Advance Green Gaffer tape , and the lid of each was made of UV-transparent Perspex which allowed observations to be made externally. Each arena also had six sliding doors, which could be opened to gain access to flight space. Outside of the trials, the nestbox had free access to the arena where pre-training stimulus flowers were present. These flowers lacked any signals that bees were tested on during learning trials, and were made from 60 ml specimen jars  with white lids holding an upturned Eppendorf tub lid . Feeding flowers had slightly varying appearances to prevent bees developing preferences for a particular flower color or feeding-well size and encourage exploration of new flowers. Once a day, flowers were filled with a 30% sucrose solution, and a further food source was provided in the form of a PCR rack filled to one third capacity with the sucrose solution. Two teaspoons of pollen were administered directly into the nests three times a week. Whilst bees were feeding in the arena outside of learning trials, individual foragers were marked using nontoxic paint of various colors to allow for visual discrimination of each bee.Three nestboxes of The artificial flowers used were constructed according to the design of the ‘passive artificial flower’ used by The internal components of each flower consisted of three 40 mm colored sponge discs , with the top-most sponge always being green to achieve visual uniformity between all flowers. These sponges were stored in their original packaging until they were required to avoid additional drying out.For each trial, four flowers of each of the dry and humid variants (described below) were set up. Specimen jars were selected so that four evenly and four oddly numbered jars were used, each type associated with a flower variant. Whether odd jars were used for humid or dry flower variants alternated with each experiment.For dry flower variants, sponge discs were cut out and placed directly into the flowers without further adjustments, followed by the securing of the gauze and lid. All lids were wiped with ethanol before being attached to remove any olfactory or chemical cues.For humid variants, sponges were thoroughly soaked before the experiments in water that had been left to adjust to the room temperature overnight in a glass jug. Each disc was wrung out under the water before placing inside the flower to achieve full saturation, before a gauze sheet was stretched over the top and secured using a lid. If the gauze sheet got wet during preparation, the sheet was discarded and a dry sheet was used so that foraging preference would not be impacted by the presence of water on the surface.Staublie RX 160 robot arm , and was roughly 1.36%. This value reflects the differences in relative humidity observed by the same authors between various flower species and between flowers and background humidity, and is, therefore, a similar value to the change in relative humidity that might be experienced by a foraging bee in the natural environment. Flowers were de-assembled and sponges re-soaked if the hygrometer did not report a 2% RH rise. In the case of the dry flower variants, the RH value of the floral headspace was recorded at the start of an experiment using the hand-held hygrometer so that the humidity produced by the dry flowers could be monitored throughout the experiment.To check that the humid variants created at least a 2% rise in relative humidity compared to background levels, a hand-operated hygrometer was used to read the relative humidity above each flower. It was also important to ensure that the two flower variants were not distinguishable by their temperature which may have occurred because of evaporation or the water temperature. A thermal imaging camera  was used to check the temperature of the landing surface of each flower. If either flower variant displayed a temperature difference of more than 1ºC, the warmer variant was placed into a 5ºC refrigerator for a few seconds. The flowers were then removed and accepted for use if the temperature difference was reduced to below 1ºC. Each flower then received an Eppendorf lid feeding well, which was loaded with either a 25 ml drop of water or 30% sucrose solution as appropriate .During an experiment, artificial flowers were removed following the end of each foraging bout, when they were cleaned to remove any olfactory cues  that migBees were assigned to one of four environmental treatment groups designed to reflect the extremes and intermediate humidity conditions that may be experienced in the natural environment. The environment treatment groups were: 1) Low humidity maintained at 20–25% RH, 2) Ambient humidity environment, maintained at 35–45% RH, dependent on the conditions in the laboratory, 3) Medium humidity environment where humidity was maintained at 67.5–72.5% RH, and 4) High humidity environment where humidity was maintained at 92.5–97.5% RH. The intensity of floral humidity produced by humid artificial flowers was the same in each environment, meaning that contrast with the background humidity would be 2% RH in the Ambient environment, but would be increased in the Low, decreased in the Medium, and decreased further still in the High. The method for setting up each treatment is described below.Humidity in the arenas was lowered using a Manli Cordless Hair Dryer . Before the start of the experiment, the hairdryer was turned on inside the empty arena with two doors open to allow air flow. The handheld hygrometer was used to observe when the arena reached 20% RH. The temperature of the arena was recorded before drying, and again after drying. As the dryer recirculated unheated air only, the temperature inside the arena remained within 3ºC of the ambient arena temperature before drying. When 20% RH was achieved, the hair dryer was turned off and removed. Artificial flowers were introduced into the arena according to the test group and a learning trial was begun.The RH of the arena in the Ambient environment group was not changed from background levels observed on the day of an experiment as relative humidity conditions inside the bee lab were controlled at roughly 40% RH, which fluctuated slightly due to changes in outside weather conditions. Therefore the parameters for the atmospheric humidity to be used in the Ambient environment group were set at within 5% of 40% RH. At the start of a trial, RH inside the arena was checked to ensure conditions were within these parameters.Humidity of the arena was elevated using a 0.5 liter Vicks Personal Humidifier  which was filled with water that had been left overnight to adjust to room temperature and placed inside the empty arena before the start of an experiment. The temperature of the arena was measured using the hand-held hygrometer, and the humidifier was turned on. The humidifier was turned off and removed from the arena once the arena had reached 72.5% RH (roughly five minutes). Temperature was monitored at this point to check that the arena temperature was within 2ºC of the ambient arena temperature, which was consistently reported given the use of room-temperature adjusted water in the humidifier. Water vapor created by the humidifier was allowed to completely settle before introducing the artificial flowers (roughly 5 min). This was done to allow full visibility to return for behavioral observations as water vapor plumes clouded the arena, and so that water vapor would not condense on the surfaces of artificial flowers, to avoid any further alterations in floral humidity being introduced or any water droplets on the surface of flowers that may affect foraging preference. The artificial flowers to be used that day were then placed inside the arena and the first foraging bout could begin.In the Humid environment treatment group, the relative humidity of the arena was raised using the Vicks Personal Humidifier as in the Medium humidity treatment. The humidifier was turned off and removed once the arena had reached 97.5% (roughly 10 min). Temperature was monitored at this point to check that the arena temperature was within 2ºC of the ambient arena temperature, which was consistently reported given the use of room-temperature adjusted water in the humidifier. As in the Medium humidity treatment, water vapor was allowed to completely settle. Artificial flowers were introduced according to the test group, and the first foraging bout was begun.Before each foraging bout , the humidity treatments were checked and then maintained as follows.Humidity was ‘topped up’ to 20% before the start of each foraging bout. Once the bee had returned to the nest, flowers were removed and for cleaning and refilling as described previously. Whilst the flowers were cleaned, the hair dryer was placed into the arena and turned on with two doors open to allow air flow. The hand-held hygrometer was used to monitor relative humidity and temperature. When humidity reached 20% RH, the dryer was removed, and temperature was checked to be within 2ºC of ambient temperature. The cleaned flowers were then returned to the arena to start the next foraging bout.Between each foraging bout, humidity inside the arena was checked using the hygrometer to check that the arena had not fluctuated outside of the 35–45% RH parameter before beginning the next foraging bout. As conditions inside the bee lab were stable, this was consistently reported.Humidity in the arena was ‘topped up’ to 72.5% RH before each foraging bout. After the flowers had been removed, the humidifier was returned to the arena and turned on whilst the flowers were being cleaned and refilled. The relative humidity and temperature were checked using the hand-held hygrometer. When humidity reached 72.5% RH, the humidifier was removed, and any water vapor was allowed to settle before reintroducing the flowers for the next foraging bout.At the end of a foraging bout humidity was ‘topped up’ to 97.5% RH. Whilst flowers were cleaned and refilled, the humidifier was placed inside the arena and turned on. The hand-held hygrometer was used to observe when humidity was at 97.5% RH, and temperature was checked to be within 2ºC of ambient temperature. The humidifier was then removed, and the water vapor was allowed to settle. The flowers were then returned to the arena for the start of the next foraging bout.Differential conditioning techniques were used to test for the ability of bees to learn the presence of a sucrose reward associated with both humid and dry flower variants in each of the environmental treatment groups as an indicator of floral humidity signal detectability. Bees came from three different nests, which were used on a rotating basis. Bees were assigned to one of the four environmental humidity treatments described above. Within each of the environments, each bee was also allocated to one of three test groups, which were 1) Control, 2) Humid rewards, and 3) Dry rewards. In the Control, all flowers were of the dry variant with dry sponges, meaning there was no humidity difference between rewarding and nonrewarding flowers. In the Humid group, the rewarding flowers were humid variants, and nonrewarding flowers were dry variants. In the Dry group, the rewarding flowers were dry flower variants, and the nonrewarding flowers were humid variants. The feeding wells of flowers held a 25 ml of 30% sucrose solution or of water depending on if they were rewarding or nonrewarding, respectively. A summary of the twelve total test groups is shown in During a learning trial, individual foragers were released alone into the arena, where they would encounter four rewarding and four nonrewarding flowers. The humidity produced by the internal components of the flowers varied according to the test group that the bee was in, and variants were recognizable to the experimenter by the odd or even numbers on the sides. Once released into the flight arena, the bee was allowed to forage on any flower. Observations were made on two foraging behaviors: 1) ‘land’, defined as the bee making physical contact with the top of the flower surface at any location even if the bee continued flying, and 2) ‘feed’, defined as the bee extending its proboscis into the feeding well. Consequently, each visit could be categorized either as 1) ‘correct’ where a bee would land and feed from a rewarding flower, or land without feeding from a nonrewarding flower, and 2) ‘incorrect’ where a bee would land and feed from a nonrewarding flower or land without feeding from a rewarding flower. These classifications reflect those used in previous conditioning studies e.g., , and takAt the end of each foraging bout, all flowers were removed and cleaned as described previously before being returned before the start of the next bout, and all feeding wells cleaned and refilled as described previously. Atmospheric relative humidity conditions were also managed at the end of each bout as described previously. A foraging bout would only begin once all flowers were cleaned and refilled, and the arena humidity was within the defined parameters.R 4.1.3 using nlme 3.1  was constructed in nlme 3.1  considernlme 3.1  demonstrns 1.7.2   or humid (orange dashed line) flowers were rewarding, with both flower types being learnt at similar rates, although the dry rewarding flowers appeared to be learnt faster in all the environments. However, in the high humidity environment, the bees appeared unable to learn that humid flowers were rewarding , whilst Signals produced by plants to attract pollinators may be vulnerable to being masked by background noise created by climatic heterogeneity . If florWe found that in high humidity environments, the bees had trouble learning that flowers presenting humid signals were rewarding. It would be tempting to explain this by suggesting that the high humidity environment may have enhanced the ‘wetness’ of the dry flowers, making it difficult to differentiate between the dry and humid forms. However, this is unlikely given that the bees were able to learn about dry rewarding flowers when in the humid environment. Similarly, the low humidity environments appeared to have no impact on bees being able to differentiate between dry and humid flowers, suggesting that any masking that might have been caused by interactions between the floral humidity and the environment was minimal. In the context of high humidity or recent rainfall pollinators may still use floral humidity to accurately determine profitability, but process humidity as a negative stimulus as has been demonstrated by pollinators switching to flowers with concentrated nectar that would be relatively drier . In thisApis mellifera L. (Hymenoptera: Apidae), firing activity of dry and moist cells is increased by 1 impulse s−1 by instantaneous humidity changes of −2.5% RH and +3.3% RH respectively (Periplaneta americana (L.) (Blattodea: Blattidae) were −1.6% RH and + 2% RH, and were −3.3% RH and +2.5% RH in stick insect Carausius morosus (De Sinéty) (Phasmida: Phasmatidae) , mealworm beetles Tenebrio molitor L. (Coleoptera: Tenebrionidae) and human lice Pediculus humanus L. (Psocodea: Pediculidae)  . Sensiti% RH s−1 . Corresp insects . Furtherculidae) . A respoculidae) .Manduca sexta (L.) (Lepidoptera: Sphingidae)  . The obsingidae) . An incrEchium wildpretii H.Pearson ex Hook.f.  is thought to function as a water reward to foraging honeybees (The local climate dictates the behavioral responses towards individual flowers and stimuli by regulating demands and preferences of foragers, and by changing floral reward status . The resoneybees . Conversoneybees . Mason boneybees . In extroneybees . In the oneybees  and acceoneybees . Therefooneybees . Dilutiooneybees . As bee-oneybees . In bothoneybees  may provEnvironmental Entomology online.Supplementary data are available at Three files are included:• R code used for processing the dataset.• The code file ‘Harrison_Rands_code.R’ is a text file containing the • A pdf ‘Supplementary.pdf’, which contains nvac049_suppl_Supplementary_MaterialClick here for additional data file.nvac049_suppl_Supplementary_DatasetClick here for additional data file.nvac049_suppl_Harrison_Rands_codeClick here for additional data file.


In this work, a stability study of dispersions of graphene oxide and graphene oxide functionalized with polyethylene glycol (PEG) in the presence of bovine serum albumin is carried out. First, a structural characterization of these nanomaterials is performed by scanning electron microscopy, atomic force microscopy, and ultraviolet visible spectroscopy, comparing the starting nanomaterials with the nanomaterials in contact with the biological material, i.e., bovine fetal serum. The different experiments were performed at different concentrations of nanomaterial (0.125–0.5 mg/mL) and BSA (0.01–0.04 mg/mL), at different incubation times (5–360 min), with and without PEG, and at different temperatures (25–40 °C). The SEM results show that BSA is adsorbed on the surface of the graphene oxide nanomaterial. Using UV-Vis spectrophotometry, the characteristic absorption peaks of BSA are observed at 210 and 280 nm, corroborating that the protein has been adsorbed. When the time increases, the BSA protein can be detached from the nanomaterial due to a desorption process. The stability of the dispersions is reached at a pH between 7 and 9. The dispersions behave like a Newtonian fluid with viscosity values between 1.1 and 1.5 mPa·s at a temperature range of 25 to 40 °C. The viscosity values decrease as the temperature increases. Nanotechnology has had a great impact in the last two decades as it offers different properties to volumetric materials. One of these nanomaterials is graphene oxide (GO), which can be obtained from graphite. Graphite can be exposed to strong oxidants that produce graphite oxide. This can be exfoliated through an acid-base treatment, producing planar monomolecular layers, which are graphene oxide .Graphene is a nanomaterial consisting of a single layer of allotropically organized carbon atoms from graphite. Each layer is composed of lattices divided into two sublattices connected by σ bonds, in which each carbon possesses free π electrons. These bonds create a high electron density both over and under the 2D layer of graphene [It is a chemically, mechanically, and thermally stable material and possesses high flexibility. Graphene has a distinct structure that confers special properties, such as a large specific area, the ability to be easily modified, and the fact that it is a long-lasting material. These properties enable graphene to act as a drug delivery vehicle .Graphene-based nanomaterials exhibit characteristics that make them very versatile and useful in a wide variety of fields, including biomedical applications, fast-charging batteries, advanced environmental photocatalysts, solar cells, and quantum physical chemistry, among others .They acquired notable attention in the field of biomedicine, such as in tissue engineering for tissue repair, regeneration of bone structures, and drug delivery . For exaGraphene nanomaterials have the ability to bind to DNA and protect it from nucleases, enzymes that degrade nucleic acids. This property has been investigated for its use in gene therapy techniques for “gene targeting”. Because it protects the DNA and promotes more efficient and easier gene fragment insertion, it allows us to ensure that the insert reaches the target site .The unique structure of graphene, as well as its C-C bonds, provide it with excellent thermal and electrical conductivity that can be useful in electronic and biomedical instruments such as biosensors . A biose2) and aliphatic (sp3) domains, which facilitate interactions at the molecular surface and can form hydrogen bridges and metal ionic bonds [GO presents a great variety of functional groups such as oxygens, epoxide groups, carbonyl, hydroxyl, and phenol groups, which are distributed along the GO surface . The mosic bonds .GO possesses properties that make it a perfect candidate for cancer therapy, using it as a drug transporter (drug delivery), as by modifying it, it can deliver the drug to its target more effectively .Surface properties determine the properties of the nanoparticles; therefore, surface modification of nanoparticles is a useful process to modify the properties of nanoparticles by adding or modifying functional groups to the surface of the NPs. Several studies have been conducted to see how we can obtain better performance or improvements through the formation of functionalized nanomaterials with other particles by surface modification ,11,12,13PEG is a very useful biological reagent due to its minimal cytotoxicity, high biocompatibility, protein resistance, and water solubility. It has been shown that, thanks to these properties, when PEG conjugates are produced with other polymers, an increase in biocompatibility is promoted .In the same way, the surface PEGylation of graphene NPs has been extensively studied, concluding that it can have a good use as a hydrophobic anticancer drug carrier in mammalian organisms ,12,14.The usefulness of NPs in biomedicine is conditioned by their behavior in biological media. The study of nanoparticle-protein interactions is essential since this will help us understand the feasibility of their use in living organisms, opening the way to new possibilities in the biomedical field.NPs are instantly modified once they come into contact with the bloodstream due to interactions with blood components. This spontaneous coating of NPs by proteins has been termed “protein corona” (PC) and is a determining factor for the pharmacology and toxicology of NPs .The first proteins that form the PC bind to the NPs very quickly because of the affinity of their amino acids and side chains for the NPs. These proteins already anchored to the surface bind, but instead of binding to the surface of the NPs, this second layer of the PC is formed by protein-protein interactions. The binding of the protein to a nanoparticle forms the complex known as NP-PC, and the characteristics of both are modified in such a way that researchers have recently begun to treat them as new NPs .During adsorption to NPs, proteins may undergo conformational modifications to rearrange their structure. Binding proteins to flat-surface NPs can lead to more abrupt structural changes in the proteins than if the NPs were curved surface. This process is thermodynamically favorable if the charged or hydrophobic sequences of the proteins coincide with the hydrophobic or charged surface portions of the NPs .The affinity competition between proteins to bind to the surface of NPs is responsible for the protein corona changing over time; this allows us to distinguish between “hard corona” and “soft corona”. The “hard corona” is considered the first protein layer that binds tightly to the NPs and is maintained for a long residence time . The “soft corona” is represented by the second protein layer, which is not directly bound to the NP and undergoes very rapid changes in short periods of time. The proteins that are bound to the NP are in a continuous desorption/adsorption flux, mainly controlled by the so-called “Vroman effect” .The composition of PC is unique for each nanomaterial and depends on its size, shape, and surface charge, as well as any surface modifications that it has and the biological environment in which it is found. Even when compared between NPs of the same material, it can vary, as it is highly dependent on the physicochemical properties of the NPs and the concentration of proteins present in the biological medium ,18.In this work, a stability study of graphene oxide and graphene oxide functionalized with polyethylene glycol (PEG) in the presence of bovine serum albumin (BSA) is carried out. Serum albumin is the most abundant protein found in blood plasma, constituting most of the plasmid fluid and playing an important role in the transport of compounds . As such2/g and an average pore size of 12.8 nm.Graphene oxide (GO) was acquired by NanoInnova Technologies SL. This GO has a specific area of 20–35 mBiological fluids, bovine serum albumin , and fetal bovine serum , were obtained for Sigma Aldrich  and Gibco , respectively.2 and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehypochlorite (EDC HCl) were purchased from Sigma-Aldrich .4arm-PEG5K-NHFor the PEGylation process of the nanomaterials, the method described by Zhu et al.  was follEDC HCl is added to the nanomaterial dispersion, which is responsible for activating the carboxyl groups of the nanomaterial. This is achieved because the amide group of the EDC captures an H proton from the carboxyl group, and the EDC and the GO nanomaterial are joined, leaving an intermediate product called o-acylisourea on the surface of the nanomaterial. The PEG has branches and a terminal amino group. This amino will react with the o-acylisourea, breaking the R-COO-R bond and forming an amide bond between the nanoparticle’s R-COO- group and the PEG’s amino group, forming GO-PEG via an amide bond. The reaction leaves urea as a residue. PEGylation of GO gives us, for each PEG molecule, 3 functional terminal amino groups on the surface of the nanoparticle. A schematic of the reaction can be seen in 2 (300 mg) is subsequently added. This mixture is sonicated in an ultrasonic bath for 5 min at room temperature. Afterwards, 30 mg of EDC HCl is added and sonicated in the ultrasonic bath for 40 min, after which EDC HCl (80 mg) is added again and left to stir overnight with magnetic stirring.A dispersion of graphene nanomaterial of concentration 1 mg/mL (100 mg suspended in 100 mL of double-distilled water) is prepared, and then 4armPEG5K-NHThe dispersion was vacuum filtered and washed with water several times. The filtration result was placed in a crystallizer and allowed to air dry for 48 h at room temperature to remove any remaining moisture. It was obtained as a black solid that corresponds to GO-PEG.Graphene oxide samples were mixed with a biological fluid to acquire suspensions with different concentrations. To obtain a high dispersion and homogenization, graphene oxide/graphene oxide pegylated dispersions were homogenized with an ultrasonic homogenizer  for 10 min using 50% power and a pulsed cycle of 1 s . Then, the biological fluid was added, and an incubation was performed. Several incubation times , different incubation temperatures , and different concentrations  were tesThe characterization of GO powder and GO-FBS dispersion were performed by Cerpa et al. in previous papers using several techniques ,20. In tScanning electron microscopy images were captured using a JEOL JSM 6335F  at 20 kV with a secondary electron detector in the Centro Nacional de Microscopía . From a diluted suspension, one drop of each nanomaterial or nanomaterial with biological fluid was placed on a stainless-steel grid with a graphite layer and dried before analysis. Ultraviolet-visible spectra were obtained by the UV-Vis spectrophotometer Jasco V-730 . Dispersions prepared in −1 in 300 s; the second stage is a plateau at 1000 s−1 for 60 s; and finally, the third stage decreases the shear rate from 1000 to 0 s−1 in 300 s.Measurements by zeta potential were carried out with a Zetasizer Nano ZS  instrument at pH values between 2.0 and 9.0. The zeta potential is connected to a MPT-2 Tritator  that perform the automatically pH regulation. A Haake RheoStress 6000 rotational rheometer , equipped with a double-cone and plate system that has a 2° cone angle and a 60 mm diameter, was utilized to acquire the rheological properties of the samples. Each sample was measured with the same protocol of three stages. The first stage involves a linear increase in shear rate from 0 to 1000 sStructural characterization was performed by scanning electron microscopy to determine information about the size and shape of the nanostructures and test the possible morphological changes produced by the BSA interaction. These measurements provide quantitative information about the stability of the samples. A study of the zeta potential of GO + BSA was performed in a pH range of 2–9. Each sample was measured three times, and the average of these three measurements is shown in Different authors consider ±25 mV as a value for assuring the stability of suspensions . It is cObtaining the spectra of the nanomaterials allows us to know their characteristic patterns, so it is possible to compare and observe the variations when the protein is added. In the spectrum corresponding to GO a,b, two In a previous work, Zhang H. et al.  demonstrHowever, in the spectra with GO-PEG and different concentrations of BSA , it is oSamples containing GO and BSA at different concentrations  show thaThe analysis of the rheological results obtained allows one to check how the addition of nanomaterials affects the physical characteristics of biological fluids, specifically their flow behavior (flow curve) and viscosity values.The viscosity curve as a function of shear rate for the GO sample at different concentrations (0.125–0.5 mg/mL) and temperatures of 37 °C can be seen in −1 was obtained for the GO aqueous dispersion at 37 °C.At low concentrations in the range of 0.125–0.5 mg/mL, the GO sample does not modify the viscosity of the biological medium. The mean value of the viscosity, 1.1 mPa·s, is close to the water viscosity, 1 mPa·s. At low concentrations in the range of 0.125–0.5 mg/mL, the GO sample does not modify the viscosity of the biological medium. The mean value of the viscosity, 1.1 mPa·s, is close to the water viscosity, 1 mPa·s. An increase in concentration has little effect at the tested ranges, and the viscosity practically does not change. A value of 1.1 mPa·s for the mean shear rate = 500 s−1 due to the interactions and aggregation that can occur between the GO, BSA, and other components of the biological medium. The viscosity value is 1.3 mPa·s for GO + BSA and GO + FBS samples and 0.7 mPa·s for GO at 200 s−1. The mean viscosity values of 1.1 mPa·s, 1.2 mPa·s, and 1.25 mPa·s for GO, GO + BSA, and GO + FBS, respectively, at 500 s−1, are obtained.The effect of the biological fluid is shown in −1.The same comparison of viscosity curves was also performed for GO-PEG , using iIn −1 are shown. When the temperature increases, the viscosity values decrease. These values are between 1.3 and 1.1 mPa·s at a shear rate = 500 s−1 for all samples studied.In The use and manipulation of materials at the nanometric level has proven to be a very useful tool and presents a wide range of possibilities. Graphene-based nanomaterials have very useful capabilities, one of the most important being the treatment of complicated diseases such as cancer. Therefore, it is essential to know how they behave in contact with biological materials.The visualization of the samples by SEM has shown that there is a change in the surface of the nanomaterials, with the formation of the corona protein being observed.Ultraviolet-visible spectrophotometry has revealed that when GO and GO-PEG come into contact with BSA, they form a complex. This indicates that protein binding to the nanomaterial is formed, showing higher absorbance at higher protein concentrations.A decrease in absorbance could be observed after 60 min of incubation. It is possible to hypothesize that this is the time when the protein desorbs from the nanomaterial.Further, it has been observed that the incorporation of PEG helps to stabilize the dispersions and increases the biocompatibility of the nanomaterial but does not lead to an increase in protein adsorption.Rheological characterization has shown that the starting samples exhibit flow behavior characteristic of Newtonian fluids with viscosity values around 1.1 mPa·s at 37 °C temperature.The PEGylated samples in the presence of BSA do not show significant changes in the viscosity values compared with the starting materials.−1.As the nanomaterial concentration increases, the viscosity also increases, but the changes are small over the range of concentrations studied for samples (GO and GO-PEG) in the presence of BSA. For the dispersions studied, it is shown that increasing the temperature decreases the viscosity. Viscosity values between 1.5 mPa·s and 1.1 mPa·s are obtained for GO and GO-PEG at a range of temperatures of 25 and 40 °C, and the shear rate = 500 sThe use of these graphene nanomaterials should be approached from a sustainable point of view. The preliminary study carried out has shown that they do not present a great risk to the environment, although more exhaustive environmental impact studies should be carried out to ensure responsible use of the nanomaterials.Looking toward the future, this work can serve as a basis for further studies on the characterization of graphene-based nanomaterials and their behavior in biological media. As described above, they have highly desirable properties for use in biomedicine, such as cancer treatment, biosensors, etc. But they have features that make them dangerous if not used within standardized parameters. They have a very promising future, so it is essential to understand them.


Explorations of indefinite nanocavities have attracted surging interest in the past few years as such cavities enable light confinement to exceptionally small dimensions, relying on the hyperbolic dispersion of their consisting medium. Here, we propose and study indefinite graphene nanocavities, which support ultra-compressed mode volumes with confinement factors up to  Optical nanocavities provide a indispensable platform to study various sorts of light–matter interactions, including light emission ,2,3, optRecently, hyperbolic metamaterials (HMMs) and metasurfaces ,21,22,23In this article, we demonstrated a novel type of graphene indefinite nanocavity consisting of alternating graphene and silicon layers. The hyperbolic dispersion of such graphene-silicon HMM allows for propagating waves with large wave vectors and high effective indexes. This leads to ultra-confined modes with volume confinement factors up to troscopy , biosenstroscopy ,48, and troscopy ,50, overd = 9 nm and its relative permittivity is set to be T is temperature; e is elementary electric charge; and ℏ is the reduced Planck constant. In this research, T = 300 K, The scheme for an indefinite graphene nanocavity is presented in ectively :(1)σintrx-y plane [z coskz-y plane : ϵx=ϵy=ϵx, y, and z-directions, respectively. We assume that Cavity modes in the graphene indefinite cavity and the iso-frequency contour of HMM are both shown in ties see b and lx=z reach almost 300. However, the quantum effect should then be taken into consideration if the distance between neighbouring graphene sheets goes into the sub-nanometer regime.The spatial distributions of the electric field for a 2D indefinite cavity see b are preon modes ,54. Inderelation :(5)kx2/ϵAs a next step, we perform simulations of a 2D nanocavity array see b with 50As a last step, we study the mode volume of graphene indefinite cavities by means of quasi-normal mode theory . Figure  Formula . In the 0−5∼10−4  and simi0−5∼10−4 . Althoug to Ref. ), the obcavities . The extcavities .In conclusion, we propose and demonstrate graphene indefinite nanocavities with ultra-compressed mode volumes and extraordinary optical confinement at mid-infrared and THz spectral regimes. The normalized mode volume can reach approximately


The observation of the Wien effect for the common case of water dissociation (H2O + + OH−) has remained elusive. Here we study the dissociation of interfacial water adjacent to proton-permeable graphene electrodes and observe strong acceleration of the reaction in fields reaching above 108 V m−1. The use of graphene electrodes allows measuring the proton currents arising exclusively from the dissociation of interfacial water, while the electric field driving the reaction is monitored through the carrier density induced in graphene by the same field. The observed exponential increase in proton currents is in quantitative agreement with Onsager’s theory. Our results also demonstrate that graphene electrodes can be valuable for the investigation of various interfacial phenomena involving proton transport.Strong electric fields can accelerate molecular dissociation reactions. The phenomenon known as the Wien effect was previously observed using high-voltage electrolysis cells that produced fields of about 10 Direct observation of electric field effects in the water dissociation reaction remains elusive. Here, the authors report an exponential acceleration of the reaction as function of the interfacial electric field using graphene electrodes decorated with Pt. Graphene is an attractive platform to study this phenomenon, known as the Wien effect4. Graphene’s electron conductivity along the direction of its basal plane displays a strong ambipolar electric field effect, which arises from the possibility of controlling the Fermi energy of the material with a gate voltage5. This allows for its use to characterise interfacial electric fields experimentally5. In the perpendicular direction to the basal plane, graphene is perfectly proton-selective—permeable to thermal protons6, but impermeable to all other ions8. Graphene is also impermeable to all atoms and molecules at ambient conditions11 and possesses exceptional mechanical strength12. These properties enable the use of graphene as a two-dimensional proton permeable electrode13. Previous work showed that in acidic electrolytes graphene electrodes allow quantifying the intrinsic proton currents arising from the hydrogen evolution reaction13. This suggests that, in principle, it should be possible to dissociate interfacial water14 into protons and hydroxide ions (H2O + + OH−)14 and measure the resulting proton currents through graphene. In this work, we measured proton transport through graphene electrodes in setups where water is the only source of protons. By in situ monitoring the electric field at the graphene-water interface, we find that the proton currents are strongly accelerated with the interfacial electric field.An electric field can dissociate a water molecule by pulling its constituent proton and hydroxide ions apart7. Typically, our devices had nine holes 2 μm in diameter each. One side of the freestanding graphene film (outer side) was decorated with Pt nanoparticles deposited by electron beam evaporation, which formed a discontinuous film  and enhance the proton conductivity of graphene6. We chose Pt as a model system to characterise the effect, but we have demonstrated that other metals  can be used as well13. The opposite (inner) side of the devices faced a 1 M KCl electrolyte with low (<10−7 M) bulk proton concentration . The high KCl concentration keeps the Debye length in the electrolyte practically constant through the whole pH range; whereas the high pH ensures that all proton currents in the device are due to water dissociation, rather than permeation of free protons present in the bulk solution. The graphene film was electrically connected to form an electrical circuit as shown in Fig. 6.The devices studied in this work Fig.  consiste2O + + OH−) at the graphene electrode is accompanied by proton transport through graphene. The transferred protons are adsorbed on the Pt nanoparticles and acquire electrons (H+ + e− → Pt-H*) flowing into graphene via the electrical circuit. Protons adsorbed on Pt eventually evolve into hydrogen molecules  and escape as H2 gas through the discontinuous Pt film6. Any other sources of current  yield negligibly small currents, as reported previously15 and corroborated using the reference multilayer-graphene devices. Note that the use of the μm-sized graphene electrodes ensures that the circuit’s resistivity is dominated by proton transfer through graphene and resistive contributions from the bulk electrolyte and large counter electrode are negligible17 .The rationale to measure interfacial water dissociation in these devices is as follows. Water dissociation 19. Hence E = ne/ε, with n the charge density in graphene, e the elementary charge and ε the dielectric constant of interfacial water. The exact value of ε remains poorly known22 and is generally expected to change under high E23, so in this work we use it as a fitting parameter. On the other hand, n in graphene electrodes can be measured directly as follows. The Fermi energy  with respect to the charge neutrality point, μe, can be extracted from the frequency of the G-peak in graphene’s Raman spectrum25. In turn, this gives n via the relation5n = μe2 (ħvF)−2, with vF ≈ 1 × 106 m s−1 the Fermi velocity in graphene and ħ the reduced Planck constant  that increased linearly with negative (positive) potentials. By tracing the potential at which the doping shifts from electrons to holes, we find that the charge neutrality point (NP) lies around −0.20 V vs Ag/AgCl. We did not observe a dependence of the NP on pH within our experimental scatter, in agreement with previous work27. The results in Fig. 11 cm−2 at the NP. This relatively low charge inhomogeneity can be attributed to a finite concentration of impurities or strain and is known to give rise to nm-sized electron-hole puddles28.An advantage of graphene electrodes is that they allow characterising electric field V-bias around the potential of zero current vs the reference electrode until the I–V stabilises and retraces itself. We attribute this stabilisation to the formation of a steady-state concentration of adsorbed protons on the Pt nanoparticles as a result of the water dissociation process. Figure I–V responses from these devices obtained at various pH. We found that the potential at zero current, φ, was typically negative and increased with pH. For small V-bias around this potential (ΔV = V–φ) the I–V response was linear, which allowed us to analyse our results in terms of the proton conductivity of the devices, GH = I/ΔV. Figure φ increased with pH and this was accompanied by an exponential increase in GH. This increase in conductivity could be reversed by lowering the pH, which allowed us to measure our devices across the whole pH range repeatedly 6 regardless of pH. This shows that 2D electrodes are necessary to observe the field effect. We attribute this to the fact that in few-layer graphene electrodes, the created proton and OH− remain within the interfacial layer and recombine. In contrast, in monolayer graphene, protons can permeate through the crystal onto the Pt nanoparticles, leaving hydroxide ions behind. This separates the proton-hydroxide ion pairs across a perfectly selective one-atom-thick interface, which prevents their recombination and yields measurable intrinsic proton currents.In a typical measurement, the potential of the graphene electrodes is swept continuously with small I–V response with pH. From these data, we extracted both μe at zero current and GH from nearly a dozen graphene devices. Figure μe increased with pH  dependence and thus an electric field effect in interfacial water dissociation in graphene devices.To investigate the field effect quantitatively, we carried out systematic studies of the dependence of the  pH Fig.  and this GH Fig. . Since E5. The gate voltage raises the μe of graphene, yielding excess charge carriers5 that, in our case, are screened by ions in the electrolyte over molecular distances19 and thus result in strong interfacial E. Increasing the pH in the electrolyte shifts the equilibrium of the interfacial reaction such that it is now balanced by a larger voltage. This voltage raises the μe of the system. The resulting E pulls water molecules apart and pushes protons through graphene, separating the generated proton-hydroxide ion pairs across the perfectly selective one-atom-thick interface. This charge separation allows us to measure the proton currents from the dissociation process, which are exponentially accelerated with E.Qualitatively, our results can be understood as follows. A voltage bias between graphene and the electrolyte solution acts as a gate voltage on the graphene-water interface, as is normally the case if a voltage is applied to graphene through any dielectric substraten from μe using the formula n = μe2 (ħvF)−2, which yields the exponential GH(n) dependence on Fig. x-axis). To convert n into E, we use E = ne/ε, with ε = ε0εr, ε0 the permittivity of free space and εr the relative dielectric constant as a fitting parameter. We then analysed the GH(E) dependence with Onsager’s theory of the (second) Wien effect, which models the generation of excess ionic charge carriers by the field3 (‘Fitting with Onsager model’ in Methods). The theory relates the ratio of proton-hydroxide ion pairs (p) with and without a field as: p(E)/p(0) = [I12]3, with kBT the thermal energy. Since7GH ∝ p, the field-dependent conductance is given by: GH(E) = GH(0) × p(E)/p(0), with GH(0) ≈ 0.1 mS cm−2 the proton conductivity at pH 7. Figure ε and the absolute value of E. Our data is consistent with 5 ≲ εr εr = 6. This yields E  that reaches ~2 × 108 V m−1 at pH 13.To gain quantitative insights, we extracted 2 gas evolving on the Pt nanoparticles across graphene as well as O2 on the Pt-wire counter-electrode. To corroborate that the water dissociation is taking place, we also measured the rates of O2 and H2 production directly, rather than inferring them from electrical measurements. For hydrogen measurements, the graphene electrode faced a vacuum chamber that was connected to a mass spectrometer, whereas the oxygen production was monitored by an oxygen-concentration sensor (Clark microelectrode) placed inside the electrolyte solution. In the absence of an applied voltage bias or for positive voltages applied to graphene, no H2 could be detected by the spectrometer, in agreement with previous studies10. For the negative polarity, both electric current and H2 flux were detected and measured simultaneously. Figure 2 molecule detected by the spectrometer, two electrons flowed through the electrical circuit. This charge-to-mass conservation is described by Faraday’s law of electrolysis: ΦH2 = I/2 F, where ΦH2 is the hydrogen flux and F the Faraday constant. Similarly, the area-normalised derivative of the oxygen concentration versus time, d[O2]/dt = ΦO2 also obeyed Faraday’s law ΦO2 = I/4 F  because the created proton and OH− remain within the interfacial layer and recombine. Hence, the field effect is not expected in any 3D electrode. The development of 2D electrodes permeable to ions other than protons would allow studying field effects in a wider variety of reactions.Our work studied interfacial water dissociation by measuring the proton currents of the reaction. We exploited the strong x on B-doped Si, purchased from Inseto Ltd.) using photolithography, wet etching and reactive ion etching, following the protocol previously reported6. Our devices typically had 9 apertures, 2 μm diameter each, as these were more robust; but we also measured devices with a single aperture of 10 μm in diameter. Au electrodes were microfabricated onto the resulting substrates using photo-lithography and electron-beam evaporation. Monocrystalline graphene obtained via mechanical exfoliation29 was then suspended over the apertures, ensuring contact between graphene and the Au electrodes  which allow the generated H2 gas to escape. We tried different Pt loadings in our devices with evaporated films of 0.3–2 nm nominal thickness. The loadings tested are limited by the following considerations. If the metal layer becomes continuous it will not only trap H2, but will also become electron conductive. In this case graphene no longer works as an electrode and we lose the ability to monitor the interfacial electric fields. For very low Pt loadings, the evolution of hydrogen into H2 is slow. Within the possible bounds, we did not find any noticeable effects of the Pt loading. The opposite side of the devices faced an Ar-saturated alkaline electrolyte consisting of 1 M KCl with KOH (0–0.1 M to set the pH of the solution from 7 to 13). The pH of the as prepared solution was checked with a pH meter and adjusted as required. To ensure contact between the graphene electrode and the electrolyte, the device was initially wet with isopropyl alcohol before letting the electrolyte solution into the reservoir. The reservoir was then flushed several times with the electrolyte solution. The whole cell was placed inside a chamber with constant argon gas circulation.Micrometre-sized apertures were etched into silicon nitride substrates  between the voltmeter and source channels set the potential vs Ag/AgCl reference into a required setpoint. Current between the graphene electrode and the counter electrode were measured synchronously. For reference, we also performed measurements using an Ivium CompactStat.h potentiostat, which gave the same results. During measurements, the graphene electrode is polarised against the reference electrode continuously. We typically scanned ±150 mV around the zero current potential (vs the reference electrode) at sweep rates of 0.01 V min−1. Note that because of the small size of the graphene electrode, the bulk electrolyte resistance does not limit the current measured in any of our experiments17. The limiting resistance (R) of a cell with a microelectrode of radius r and electrolyte conductivity κ is given by R = (4πκ r)−1. In our measurements, we used 1 M KCl electrolyte that had κ ≈ 0.1 S cm−1. Therefore, for r = 1 μm the cell resistance was R ≈ 0.88 kΩ (there were nine apertures with r = 1 μm in each of our devices). This value is 3–5 orders of magnitude smaller than any of the R reported for our graphene devices.In the experiments, we measured the G-band of graphene as function of applied V using a 532 nm laser. We used an Ag/AgCl pseudo-reference electrode to apply voltage. From the shift in the G band (ΔωG), it is possible to obtain the Fermi energy of electrons in graphene (μe) and the charge carrier concentration (n), which are related to ΔωG via the following well-established relations25. For electrons, μe [meV] = 21 ΔωG + 75[cm−1]; for holes, μe [meV] = −18 ΔωG − 83[cm−1] and in both cases, the carrier density is given by n [cm−2] = (μe/11.65)2 x 1010. From measurements of four different devices, we found that the neutrality point (NP) was −0.21 ± 0.08 vs Ag/AgCl. To extract the dependence of n on applied V, the ΔωG data of all the devices was centred on the average NP. The relation found was n × |V − NP | −1 = 1.106 × 1013 cm−2 V−1.For Raman measurements, the devices were mounted in a custom-made optical cell. The outer side of the suspended graphene electrode faced upwards, towards a Raman microscope. The inner side faced a reservoir containing the electrolyte solution. To ensure contact between the graphene electrode and electrolyte, the devices were initially wet with isopropyl alcohol before letting the electrolyte solution into the reservoir. In the experiments, we measure the position of the GH(n). All the experimentally accessible parameters in the Onsager model are contained in the variable x = e3E/[8πε(kBT)2]. Because the interfacial electric field (at 1 M electrolyte concentration) is given by a simple parallel-plate capacitor, E = ne/ε, we can express x as a function of n. This allows fitting the Onsager model to our GH(n) data with ε as the only fitting parameter. Once ε is extracted, E is uniquely determined from the known n by E = ne/ε.The experimental data set used to fit the model is the proton conductivity as a function of the interfacial charge carrier density, 31. There are two possible sources of spatial inhomogeneity of E. The first is inhomogeneous doping coming from Pt nanoparticles, but this is unlikely to create an electric field at the water interface and affect our results. The second source is an inhomogeneous charge distribution caused by graphene’s morphology, which is also expected to cause some field inhomogeneity. Indeed, graphene membranes are never perfectly flat but exhibit nanoscale ripples with and even without Pt particles32. The electric-field lines would tend to concentrate on top of such ripples and create an inhomogeneous distribution of charge, which is known to influence electron transport in graphene28. Whichever the cause of field inhomogeneity, we can estimate its magnitude from the observed smearing of the neutrality point (NP) in the Raman spectra. If the doping distribution was spatially homogenous, the charge density measured at the NP would approach zero. However, we observe n ≈ 4 × 1011 cm−2 at the NP . The resulting electric-field inhomogeneity introduces notable scatter in our water dissociation data in Fig. E and at low pH. Having said that, the Raman data in Fig. E (high pH) in Fig. It is instructive to consider the role of spatial homogeneity of the electric field in our devices, which is relevant to analysis of the field effect NP Fig. . This n 2 and H2 production in our devices directly. For this experiment we employed devices with 10 μm diameter graphene electrodes to generate enough gas to be detected with mass transport techniques. Because of the large size, the inner side of the graphene electrode was coated with an anion-exchange ionomer solution , before putting it in contact with the electrolyte solution. The polymer provided structural support for the 10 μm diameter devices and, also, was an excellent hydroxide ion conductor33. I–V characterisation found that the devices displayed the same response as those without the polymer, except for pH ≲ 10 where they yielded higher currents. This difference is attributed to fixed charges in the anion-exchange polymer33.We measured the rates of O6. The device separated two chambers. The Pt-decorated side of the device faced the inside of a chamber evacuated and connected to the mass spectrometer. The opposite side of the device faced the electrolyte solution. A voltage bias was applied across the device and the hydrogen flux and electric current were measured simultaneously. Supplementary Fig. 34), a needle connected with an Argon supply and a Pt wire electrode. The outlets were sealed with gaskets. A small magnetic stir bar was put inside the chamber and kept at a rotation rate of 300 rpm to promote gas convection in the solution. For measurements, the container was filled with the electrolyte solution through one of the outlets. The solution was then purged with argon gas through the needle for at least 30 min. To prevent oxygen leakage into the cell, the whole container was placed inside a chamber with constant argon gas circulation. Both current and oxygen concentration [O2] were measured simultaneously as a function of applied bias.The hydrogen flux was measured using a mass spectrometer (Inficon UL200 Detector). Supplementary Fig. 35. This creates a chamber with a stable electrolyte reservoir for the electrodes. During operation, the potential of the sensing cathode is polarized at −0.8 V against an Ag/AgCl reference electrode. The diffusion of oxygen through the membrane can then be detected by the sensing cathode, via the oxygen reducing reaction: −. We gradually increased the pH of the tested solution by adding Ar-saturated KOH-solution until we reach pH 14. As expected, the sensor was completely insensitive to the concentration of OH− in the electrolyte solution, which demonstrates that the sensor responds only to oxygen concentration changes, as expected.Let us describe the function of our oxygen sensor in more detail (Supplementary Fig. Supplementary InformationPeer review file


Hydrogels have emerged as promising materials for the construction of skin-like mechanical sensors. The common design of hydrogel-based artificial skin requires a dielectric sandwiched between two hydrogel layers for capacitive sensing. However, such a planar configuration limits the sensitivity, stretchability and self-healing properties. Here, we report the design of single-layer composite hydrogels with bulk capacitive junctions as mechanical sensors. We engineer dielectric peptide-coated graphene (PCG) to serve as homogenously dispersed electric double layers in hydrogels. Any mechanical motions that alter the microscopic distributions of PCG in the hydrogels can significantly change the overall capacitance. We use peptide self-assembly to render strong yet dynamic interfacial interactions between the hydrogel network and graphene. The resulting hydrogels can be stretched up to 77 times their original length and self-heal in a few minutes. The devices can effectively sense strain and pressure in both air and aqueous environments, providing tremendous opportunities for next-generation iontronics. Single-layer composite hydrogels with bulk capacitive junctions were engineered as highly stretchable, self-healing, and printable artificial skins for multi-modal mechanical sensing by dispersing dielectric peptide-coated graphene in the gel matrix. Human skin combines outstanding mechanical properties with multifunctional sensing abilities. These characteristics have inspired the development of artificial skin-like materials for flexible electronics with various advanced applications in soft robotics ,2, humanDespite the tremendous success of such designs, creating hydrogel artificial skin that is stretchable and self-healable so that it can repair unexpected internal or external damage and recover critical functions similar to human skin remains challenging . First, Here, we propose a single-layer hydrogel artificial skin, termed ‘SHARK’, which combines high stretchability, self-healing properties and ultrasensitive mechanical sensing. In sharp contrast to traditional artificial skin of sandwich structures and integrated mechanical sensing, SHARK can be considered a bulk junction of hydrogel capacitors, analogous to the structure of bulk polymeric solar cells . The eleUnlike the traditional sandwich sensor with conductive layers acting as the electrode slab Fig. a, SHARK Bombyx mori silk protein and can typically form β-sheet structures [−1 . GAGAGY is a self-assembling motif derived from ructures . A pyrenructures . The pepructures . We next−1 (64% yield) for the initial graphite concentration of 1.0 mg mL−1, higher than those produced with the assistance of other biomolecules (Table S1). Another remarkable feature of PCG is its long-term stability, which ensures high mechanical and electrical stability of SHARK. The concentration of the as-prepared PCG solutions showed no obvious decrease in one month  and decreased by less than 30% after 90 days at room temperature, as estimated by UV spectroscopy . Moreover, the PCG solutions can be concentrated to 6 mg mL−1 without aggregation. However, as the interfacial bonding between the peptide and graphene is dynamic and reversible, the peptide may occasionally dissociate from the graphene surfaces, leading to slight aggregation of graphene during the long-term storage.Next, we prepared PCG by direct aqueous exfoliation of graphite via ultrasonication. Inspired by previous studies using proteins and peptides as dispersants to obtain high-quality graphene , we deve3 defects based on Raman spectroscopy , X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy Fig. b–e. Our opy Fig. f. The ch−2) at room temperature. Stable hydrogels were formed, and the color darkened with increasing PCG content . Note that the Young's modulus and fracture strain depended on the deformation rates, indicating that the rupture of peptide-graphene interactions in hydrogels is a nonequilibrium process . The hydrogel can maintain its reversibility in the range of ∼0–500% and showed larger hysteresis at higher strains in the stretching-relaxation curves, indicating that the interactions between Py and graphene can be ruptured to dissipate energy and prevent crack propagation .The mechanical properties of SHARK were quantitatively measured by standard mechanical tensile tests. Typical tensile stress-strain curves are shown in Fig. −0.5, and the capacitance increases by a factor of deformation ratio. The observed strain-dependent capacitance verified this mechanism  when exposed to an acoustic wave  of ∼32 dB , fully consistent with the analogue simulation results  was added during the preparation of SHARK used in water to enhance the erosion resistance . The sensor can fiducially resolve the same stretching, compression and finger bending motions in water despite the maximal capacitive variation percentage decreasing . Moreover, SHARK was designed to directly sense microflows in water , illustrating the great mechanical self-healing properties of SHARK.Because of its single-layer structures, the mechanical and electrical properties of SHARK-based sensors were fully self-healable. As illustrated in Fig. ele as the proportion of capacitance recovered with respect to the initial value of the pristine sample before cutting. ηele remained as high as 90% when successively dividing and rejoining the devices at the same location 10 times, demonstrating the great electrical self-healing properties of SHARK. Furthermore, the sensing capability of healed band-shaped SHARK was also fully restored after cutting/healing cycles .Figure More importantly, SHARK was remoldable because the interactions between the peptide and graphene are non-specific and reversible Fig. f and g. In this work, we have demonstrated successful design of single-layer hydrogel artificial skin, or ‘SHARK’. In contrast to the sandwich structure of the widely used hydrogel-based capacitive artificial skin, SHARK contains only a single hydrogel layer with interconnected microcapacitors formed by dielectric molecule-coated conductive sheets (i.e. graphene). Unlike typical three-layer sandwich-shaped capacitive mechanical sensors, in which the overall capacitance is proportional to the surface area of the hydrogel layer and reversely proportional to the thickness of the elastomer layer, the capacitance of ‘SHARK’ is determined by the spatial distribution of the graphene sheets in the hydrogel network. Any minute structural changes to the overall 3D hydrogel network can lead to a drastic change in capacitance over the two electrodes. Moreover, the coated peptide fibers not only increase the dielectric constant but also increase the water solubility and prevent restacking of the graphene layers. Such a design greatly improves the sensitivity and allows complete self-healing of mechanical and electrical properties after damage. The strain sensing range, sensitivity and self-healing ability of SHARK outperform most of the other capacitive strain sensors reported so far in the literature (Table S4).Although graphene/graphene oxide-peptide based hydrogels have been reported in quite a few cases , the rep−1) does not change too much upon stretching and is more than one order of magnitude lower than that of graphene-based conductive hydrogels [The mechanical sensing mechanism of SHARK is based on a change in capacitance, which is also distinct from other graphene-containing hydrogel sensors that are based on a change in conductivity. As all graphene sheets in SHARK are mostly covered by dielectric self-assembled peptide fibers, the graphene sheets are well separated. Therefore, the conductance of SHARK is contributed by the mobile ions in hydrogels rather than conductive graphene layers. The conductance . Despite water loss changing the capacitance value of the device, the ratio of the capacitance change (ΔC/C0) does not vary too much. Moreover, unlike other physical hydrogels, SHARK erodes very slowly in water because of the strong interfacial bonding between peptide and graphene. These properties ensure short-term use of SHARK for mechanical sensing. To use the sensor for long-term applications, the stability of the hydrogels can be further improved by laminating a surface-bonded elastomer layer, which will be our next endeavor.In summary, in this work we demonstrated the design and engineering of a single-layer hydrogel artificial skin that is strong, tough and able to fully self-heal its mechanical and electrical properties after damage. We illustrated successful applications of the hydrogels as strain and pressure sensors for complicated motion monitoring, sound sensing and flow detection in air or water. The great processability of SHARK in both bulk remolding and 3D printing allows construction of designer self-healable sensor chips. With the improved mechanical, electrical and self-healing properties, we expect this novel capacitive hydrogel sensor to have broad applications in next-generation flexible iontronics.−1 with a nitrogen dryer. In a typical preparation of hydrogels, acrylamide was dissolved in a PCG dispersion to a concentration of 225 mg mL−1. The mixture was degassed for 30 min by blowing argon. LAP was added to a concentration of 1.0 mg mL−1 as a photoinitiator for acrylamide and Py-GAGAGYK-ACLT. The mixture was placed under ultraviolet light  for 0.5 h to finish the copolymerization. The temperature increase brought by the heat effects was ∼3–4°C and did not lead to degradation of the peptide. Because the peptide self-assembly is achieved before the addition and copolymerization of acrylamide, the β-sheet structures of the peptide is still kept in the presence of (poly)acrylamide. The resulting hydrogel was stored under seal at room temperature before the mechanical tests. For hydrogels used in aqueous measurements, additional bisacrylamide (0.5% w/v) was added to improve the stability of hydrogels in water.To obtain the PCG dispersion for hydrogel preparation, Py-GAGAGY-ACLT instead of Py-GAGAGY was used in exfoliation of graphene so that the peptides on the graphene sheets could integrate with the polyacrylamides via copolymerization. Then, the obtained PCG dispersions were concentrated to a PCG concentration of 6 mg mL−1 (4.0 mm mm−1 min−1). The strain, λ, was defined by the distance displacement between the two clamps when the gel was deformed, divided by the distance when the gel was undeformed. The Young's modulus corresponded to the approximate linear fitting value under 1 mm mm−1 strain deformation. The toughness was calculated from the area below the tensile stress-strain curve until fracture. For the healing experiments, SHARK bands were cut into pieces and pressed after bringing the cut pieces back into contact at room temperature in air.Tensile stress-strain measurements were performed using a tensile-compressive tester (Instron-5944 with a 10 N sensor) in air at room temperature. Unless otherwise noted, the strain rate of stretching was maintained at ∼10 mm min 000 Hz unless otherwise stated. The data were collected with a custom-written LabView script. The capacitance vs strain was recorded by coupling the LCR meter with the tensile/compressive tester . For the motion sensing at different modes, the capacitance vs different stimulations  were recorded and analyzed with Igor 6.0 .All electrical tests were performed with an LCR meter  in air at a voltage of 1 V and a frequency of 100nwab147_Supplemental_FilesClick here for additional data file.


Based on nonequilibrium molecular dynamics (NEMD) and nonequilibrium Green’s function simulations, the interfacial thermal conductance (ITC) of graphene/h-BN in-plane heterostructures with near-interface defects  is studied. Compared to pristine graphene/h-BN, all near-interface defects reduce the ITC of graphene/h-BN. However, differences in defective structures and the wrinkles induced by the defects cause significant discrepancies in heat transfer for defective graphene/h-BN. The stronger phonon scattering and phonon localization caused by the wider cross-section in defects and the larger wrinkles result in the double-vacancy defects having stronger energy hindrance effects than the monovacancy defects. In addition, the approximate cross-sections and wrinkles induced by the 585 and f5f7 double-vacancy defects provide approximate heat hindrance capability. The phonon transmission and vibrational density of states (VDOS) further confirm the above results. The double-vacancy defects in the near-interface region have lower low-frequency phonon transmission and VDOS values than the monovacancy defects, while the 585 and f5f7 double-vacancy defects have similar low-frequency phonon transmission and VDOS values at the near-interface region. This study provides physical insight into the thermal transport mechanisms in graphene/h-BN in-plane heterostructures with near-interface defects and provides design guidelines for related devices. As typical two-dimensional 2D) materials, graphene and h-BN have outstanding physical and chemical properties, as well as potential application prospects ,2,3,4. HD materia3 bonds on the thermal transport of bilayer graphene/h-BN in-plane heterostructures explored through molecular dynamics (MD) simulations. When the concentration of interlayer sp3 bonds is lower than 2%, the ITC is reduced, which indicates that the sp3 bond has a defect effect. The coupling of sp3 bonds and defects can result in a defect amplifier effect. It is of great significance to fully analyze and understand the influence of defects on the ITC of graphene/h-BN in-plane heterogeneous interface.The vertical graphene/h-BN van der Waals heterogeneous interface is formed by weak van der Waals forces, and the heat transport at the interface is greatly restricted . The graHerein, the effects of monovacancy defects and 585 and f5f7 (5555-6-7777) double-vacancy defects on the ITC of graphene/h-BN in-plane heterostructures are investigated by NEMD and nonequilibrium Green’s function simulations. Three different kinds of defects are regularly distributed in the interface area. The defective structures, interfacial wrinkles, phonon transmission and vibrational density of states (VDOS) are used to analyze the mechanism of interface heat transfer. Our research aims to provide a theoretical guidance for the thermal management of graphene/h-BN in-plane heterostructure-based electronic devices.The interfaces of the graphene/h-BN in-plane heterostructures include zigzag interfaces and armchair interfaces. Furthermore, zigzag interfaces can be divided into two bonding types, namely boron atoms are bonded with carbon atoms at the interface and nitrogen atoms are linked with carbon atoms at the interface. Since the zigzag interfaces with either boron–carbon or nitrogen–carbon links have smaller formation energy values than that of the armchair interface, the former is more likely formed. Researchers have mostly focused on the heat transfer of graphene/h-BN in-plane heterostructures with zigzag interfaces ,25,26. Hx-axis direction is set as the heat flow direction with heat flowing from the graphene to the h-BN. The y-axis is parallel to the graphene/h-BN interface. The atoms of two hexagon widths at the ends of the heat flow direction are fixed to prevent atomic drift. After minimizing the energy of the system by iteratively adjusting the atomic coordinates, the system relaxes in the NVT ensemble at a temperature of 300 K and with a time step of 0.5 fs for 1 ns. When the system temperature reaches 300 K and fluctuates for an extended time, this indicates that the system has reached the equilibrium state. After this, the system is transferred to the NVE ensemble and continues to relax for 0.5 ns. Then, the NEMD simulation is performed, and a heat source and heat sink with five hexagonal widths at each end of the heat flow direction are introduced using the Langevin thermostat [T at the interface. The ITC can be obtained from the ratio of the heat flow density J(t) and the temperature jump ∆T as follows:S is the cross-sectional area at the interface, the thickness of which is 0.34 nm [Here, the large-scale molecular dynamics simulations (LAMMPS) package  is used ermostat . It shouermostat . After r 0.34 nm ,35; m1 a2 orbital hybridization in graphene, with configurations of nonhexatomic ring, point or line domain voids. The other group contains externally introduced defects, which are caused by noncarbon atoms being covalently bound to the carbon atoms in graphene. Due to the different atomic types, the external atomic defects strongly affect the charge distribution and properties of graphene.Many graphene-like materials, such as 2D graphene/h-BN, 2D nitride and 2D oxide, can be grown from the surface or interface of a substrate using chemical vapor deposition (CVD) ,37. HoweThe intrinsic defects include the SW defect, monovacancy defect, double-vacancy defects (such as 585 and f5f7) and line defects. They have their own unique structures and formation energy levels, as well as thermal stability at room temperature ,39,40. T2K, which is in good agreement with the previous molecular dynamics simulation results [10 cm−2 to 1.8 × 1011 cm−2, the thermal conductivity changes from ∼(1.8 ± 0.2) × 103 W/mK to ∼(4.0 ± 0.2) × 102 W/mK. In addition, it is found that the reduction in ITC of graphene/h-BN with double-vacancy defects is greater than that with monovacancy defects, while the ITC of graphene/h-BN with either 585 double-vacancy defects or f5f7 double-vacancy defects differ little with different numbers of defects. In order to clarify the mechanism behind the changes in ITC, the defects and induced wrinkles in models as well as the corresponding phonon transmission and VDOS are further analyzed.Here, the ITC values of pristine graphene/h-BN and graphene/h-BN with different defect types and numbers of defects at room temperature (300 K) are calculated. The results are summarized in  results ,26,45. F results  found th results  studied The decrease in ITC arises from the weakening of the phonon transport capacity caused by the near-interface defects and the wrinkles in the near-interface region induced by the near-interface defects.When phonons hit graphene defects during the transport from the heat source to the heat sink, some phonons can move forward through the defects without changing the transport direction or by changing the direction at a small angle, while others would change the transport direction at a large angle or even move backward, producing scattering. Scattering is the intrinsic mechanism of defects affecting heat transfer characteristics. Our analysis indicates that the size of the cross-section of the defect is positively correlated with the scattering ability. For 2D materials, the cross-section of the defect can be measured by the width of the defect in the direction perpendicular to the transmission path. If the cross-section is larger, more phonons would be scattered at the defects. However, more phonons would pass smoothly on the sides of the defects without being affected by the defect when the cross-section is decreased. Therefore, it can be expected that the larger the cross-section of the defect, the more difficult the heat transfer will be. As the parallel lines show in Further, the effect of wrinkles in the models on the ITC is analyzed. The wrinkles are caused by the presence of defects leading to regional restructuring, which further causes level protrusions. Similar phenomena have been observed in previous experiments . ResearcT is the system temperature, w represents the phonon frequency, w and w from the left and right contacts, respectively. Here, The nonequilibrium Green’s function is an effective method for studying quantum heat transport in nanosystems ,50. In t3 for the maximum stress and 0.5 Å for the maximum displacement, while the Monkhorst–Pack grid is set to 12 × 12. The potential is the same as that used for the ITC calculation based on molecular dynamics.In order to further illustrate the effects of the defects and wrinkles induced by the defects on phonon transport at different frequencies, phonon transmission values in the near-interface regions of pristine graphene/h-BN and graphene/h-BN with twelve monovacancy or double-vacancy defects at different frequencies are calculated. The basic structure of the graphene/h-BN in-plane heterogeneous interface is constructed according to the computational requirements of the phonon transmission function. The phonon transmission coefficients in the near-interface regions of pristine graphene/h-BN and graphene/h-BN with twelve defects are shown in N is the total number of atoms, w refers to the phonon frequency and ith atom at time t. When VDOS(w) has a higher value, this indicates that more states are occupied by the phonon with frequency w. When VDOS(w) is equal to 0, there is no phonon at frequency w inside the system.The differences in ITC values between pristine graphene/h-BN and graphene/h-BN with different defects can be further attributed to the VDOS. The VDOS is obtained from the Fourier transform of the velocity autocorrelation function of all atoms :(6)VDOS(As shown in The above phonon transmission results show that the phonon frequencies with thermal conduction contributions in graphene/h-BN are in the range of 0–37 THz, which is consistent with the phonon frequencies of the out-of-plane VDOS. Therefore, the out-of-plane VDOS results for pristine graphene/h-BN and graphene/h-BN with twelve defects are compared. To conclude, the ITC values were studied for pristine graphene/h-BN and graphene/h-BN with near-interface defects. The graphene/h-BN with near-interface defects had a lower ITC, indicating that it has potential applications in thermoelectric devices. Differences in defective structures and the wrinkles induced by the defects caused significant discrepancies in heat transfer for the defective graphene/h-BN. The ITC values for pristine graphene/h-BN, graphene/h-BN with monovacancy defects and graphene/h-BN with double-vacancy defects decreased sequentially, while the 585 and f5f7 double-vacancy defects had similar heat-blocking ability. Through the analysis of defective cross-sections, wrinkles induced by defects, phonon transmission and VDOS, the underlying mechanism of the reductions in ITC of graphene/h-BN in-plane heterostructures with near-interface defects was confirmed. It was found that the double-vacancy defects have a wider cross-section, larger wrinkles and fewer C–C bonds than the monovacancy defects, causing stronger phonon scattering and phonon localization as a direct result of a reduction in phonon transmission in low-frequency region and a decrease in out-of-plane VDOS. In addition, the 585 and f5f7 double-vacancy defects have similar cross-sections, and the phonon transmission and out-of-plane VDOS in the low-frequency region are similar; thus, they have similar heat-hindering abilities. The results in this paper provide theoretical guidance for the further utilization of graphene/h-BN in-plane heterostructures with near-interface defects.