Refugees are confronted with the task of adapting to the long-term erosion of psychosocial systems and institutions that in stable societies support psychological well-being and mental health. We provide an overview of the theoretical principles and practical steps taken to develop a novel psychotherapeutic approach, Integrative Adapt Therapy (IAT), which aims to assist refugees to adapt to these changes. This paper offers the background informing ongoing trials of IAT amongst refugees from Myanmar.A systematic process was followed in formulating the therapy and devising a treatment manual consistent with the principles of the Adaptation and Development After Persecution and Trauma (ADAPT) model. The process of development and refinement was based on qualitative research amongst 70 refugees (ten from West Papua and 60 Rohingya from Myanmar). The therapeutic process was then piloted by trained interventionists amongst a purposively selected sample of 20 Rohingya refugees in Malaysia.The final formulation of IAT represented an integration of the principles of the ADAPT model and evidence-based techniques of modern therapies in the field, including a transdiagnostic approach and the selective use of cognitive behavioural treatment elements such as problem-solving and emotional regulation techniques. The steps outlined in refining the manual are outlined in relation to work amongst West Papuan refugees, and the process of cultural and contextual modifications described during early piloting with Rohingya refugees in Malaysia.IAT integrates universal principles of the ADAPT model with the particularities of the culture, history of conflict and living context of each refugee community; this synthesis of knowledge forms the basis for participants gaining insights into their personal patterns of psychosocial adaptation to the refugee experience. Participants then apply evidence-based techniques to improve their capacity to adapt to the serial psychosocial changes they have encountered in their lives as refugees. The overarching goal of IAT is to provide refugees with a coherent framework that assists in making sense of their experiences and their emotional and interpersonal reactions to the challenges they confront within the family and community context. As such, the principles of a general model (ADAPT) are used as a springboard for making concrete, manageable and meaningful life changes at the individual level, a potentially novel approach for psychosocial interventions in the field. We describe the early development of a psychotherapeutic approach which focuses on the stressors and adaptive difficulties caused by the undermining of the core psychosocial systems during the course of the refugee experience. Our approach, referred to as Integrative Adapt Therapy (IAT) is based on the Adaptation and Development After Persecution and Trauma (ADAPT) model Silove, . In thiset al., et al., et al., et al., Refugees and conflict-affected populations manifest a wide range of both normative and maladaptive emotional, behavioural and social reactions to the combination of challenges they face including exposure to trauma, ongoing living difficulties and loss of the psychosocial support systems that usually assist in maintaining the psychological equilibrium in the individual  , their personal responses , their perceptions of and capacity to cope with the current situation, and their anticipation of coping with future challenges. The treatment goal is to draw on the enhanced understanding of these issues to develop adaptive coping skills in order to address present problems and help navigate future challenges. Although often extending beyond the core objective, extant approaches to CBT, including trauma-focused CBT, tend to focus primarily on addressing maladaptive cognitive and behavioural patterns of responding to trauma and its aftermath. The techniques used to do so are based on general principles of CBT and may not be fully contextualised in relation to the lived experience, cultural background and experience of mass violence that characterise the refugee experience. In that sense, IAT makes more explicit an ecological perspective in tracing in a thematic manner the major disruptions in psychosocial support systems that the refugee has experienced through his or her trajectory of displacement. In each case, the emphasis may differ. For example, for some, a major concern may be the interpersonal difficulties encountered by the person's expression of anger and aggression, a pattern that may be traceable to a past history of recurrent exposure to acts of injustice (ADAPT Pillar III) occurring across several phases of the refugee trajectory. At the existential level, the person may be encountering difficulties in reconciling pre-established beliefs with the abuses they have experienced, making it difficult to retain a sense of faith in humanity and life in general, a problem located within ADAPT Pillar V. Existential doubts may be regarded as one of the ‘stuck points’ within CBT, whereas these concerns are seen as central to the refugee experience and a direct focus of IAT.In the process of adapting IAT to each refugee group, background work is needed to ensure that the terminology used is culturally appropriate, ideally including indigenous metaphors to facilitate understanding of key concepts. Given that the emphasis of IAT is on facilitating a deep understanding of the sources of distress and the aim is to build adaptive capacity in a manner that is flexible and responsive to the changing environment, the expectation is that the approach may have an enduring effect on recovery in a setting where refugees are likely to encounter further and potentially novel challenges.The lead author  and DS (a psychiatrist) at the School of Psychiatry, University of New South Wales, both with extensive experience in refugee mental health and psychotherapy, developed the template for IAT based on the ADAPT model. As far as possible the principles and theoretical perspectives offered by the ADAPT model with evidence-based techniques that support therapeutic change, the overall process being tailored to the culture and context. Iterative changes were made to refine the manual with the aim to achieve a high standard in relation to ensuring the theoretical coherence of the approach overall; practicalities of application including ease of translation and comprehensibility; harnessing the potential for cultural/contextual adaptability; and in framing the material and process in a way that would facilitate task-shifting to community workers with no previous training in mental health.The initial field work was conducted amongst ten refugees trained as psychosocial workers, drawn from the displaced West Papuan community in Kiunga, Papua New Guinea (between January and March 2016). Kiunga is a remote border town where a substantial community of West Papuan refugees has resided for some years. We conducted four focus groups in which workers were asked to evaluate and assist in modifying the working manual to make it culturally and contextually relevant, based on six criteria: comprehensibility, usefulness, ease of application, ease of translation, contextual applicability and sustainability.Prior to adapting IAT for refugees from Myanmar, the in-country team  conducted an epidemiological study amongst the Rohingya group . The survey was conducted by a team of ten Rohingya researchers who were later selected and trained as IAT counsellors. The programme of research was based on a long-term engagement and partnership between the UNSW team and key stakeholders including UNHCR Malaysia, Perdana University, and the Rohingya Society, Malaysia.et al., Between October 2016 and September 2017, drawing on the experience and modifications of the IAT approach undertaken with the assistance of West Papuan refugees in Papua New Guinea, the treatment manual was adapted to the context and cultures of three refugee groups from Myanmar, the Chin, Kachin and Rohingya in Malaysia, the equivalent process being implemented subsequently amongst Rohingya living in refugee camps in Bangladesh. Prior to the adaptation, the treatment manual was translated into Bangla, the closest written language to the Rohingya dialect which lacks a standard written format. Drawing on our prior experience of adapting IAT amongst West Papuan refugees, we aimed to test using a qualitative approach: (1) whether the basic tenets of the ADAPT model could be understood by the Rohingya and resonated with their experiences as refugees in Malaysia; and (2) whether the community showed a high degree of receptivity and affinity for the treatment in relation to its cultural congruence, capacity to bring meaning to their lived experiences of conflict and persecution, and relevance to the conditions of displacement confronted by refugees in that setting.Two training workshops for the Rohingya team were conducted by AKT and two bilingual clinical psychologists (MAAM and SK), between July and September 2017.n  =  25); in addition, one focus group was conducted with ten trained Rohingya IAT counsellors. Both focus groups were conducted in Bangla and Rohingya by two bilingual clinical psychologists (MAAM and SK).Following a systematic process of adaptation, we conducted five focus groups with Rohingya refugees, comprising five persons in each group . Feedback sessions during this period led to further adaptations to the language, format and delivery of IAT. Specifically, the length of IAT was reduced from seven to six sessions, combining the first psychoeducation with the second safety/security sessions. A more flexible approach was introduced to allow an early decision to be made in therapy concerning which of the core pillars should be highlighted based on the participant using a visual grid of the ADAPT domains in which problems were prioritised. The grid provided the road map to guide the focus and sequencing of subsequent sessions. The visual representations and analogies used to illustrate the ADAPT model were all well received by participants with minimal suggested modifications. The language of delivery was simplified and de-medicalised further to emphasise the psychosocial aspects of IAT. In addition, emphasis was given to the partnership between counsellor and participant in which the two worked collaboratively to develop an understanding of the latter's life trajectory according to the ADAPT framework as the foundation for building the participant's capacity to adapt to the evolving context and challenges in their ongoing lives.The qualitative data obtained from the focus groups assisted in the refinement of both the content and format of the manual developed and piloted with West Papuan refugees. For example, after several trials, it was agreed that the individual session length of 45 min was most appropriate. Throughout the process, attention was given to ensure the accessibility and comprehensibility of all aspects of IAT given that the approach was designed for use by lay counsellors, consistent with the principle of task-shifting. The language of the manual was simplified, and technical terms were replaced with colloquial expressions and analogies, for example, recognised terms such as ‘thinking differently’ was used for cognitive re-appraisal, and the metaphor of re-building or repairing the foundations of a house for the ADAPT pillars. A Problem Pie (based on the five ADAPT pillars) provided a further visual representation of the five inter-related domains that were undermined. This was supplemented by the Happy House built on a foundation of five pillars each reflecting an ADAPT domain. The motif conveyed the key message that recovery was an active process of rebuilding all pillars simultaneously. The aforementioned ADAPT grid allowed participants to consider several inter-related issues: (1) defining the contextual and individual challenges pertaining to each ADAPT pillar and the ecological and social consequences in each context associated with the erosion of that pillar; (2) the associated maladaptive reactions each person may be showing as a consequence of the erosion of one or more pillars; (3) internal and external barriers to making positive individual changes to address or mitigate maladaptive response patterns; (4) strategies and tools to achieve change and how each may best be used in focusing on priority issues; and (5) practical methods for practicing strategies for change, for example, using coping cards containing positive statements to prompt the person to take appropriate actions when these challenges  arise. The treatment process of IAT is described in The preliminary work indicated the need to establish clear goals and expectations at the outset of IAT. In so doing, the psychosocial effects of conflict and displacement at the individual, family and community levels were ordered by the participant and the bridges identified that demonstrated how the erosion of the ADAPT pillars impacted on all these levels, a principle emphasised throughout IAT. In that sense, participants recognised that the process of achieving durable individual adaptations will benefit the system as a whole, a principle that resonated strongly with the world view of collectivist societies such as the Rohingya.Refugee Mental Health Assessment Package (R-MHAP): To assess comorbid mental disorders, we included key assessment modules of the R-MHAP, designed specifically for use with refugees  which comprises five independent subscales – safety and security; bonds and networks; access to justice; roles and identities; and existential meaning – designed to measure therapeutic outcomes and progress in managing stress reactions associated with the ADAPT-related challenges , a Muslim Rohingya man who fled persecution after experiencing extreme traumatic events in Rakhine state. He experienced great peril during the flight and conditions of severe deprivations after crossing the border. In this instance, the foundation of the ADAPT house was likened to bamboo pillars, a widely used construction material for Rohingya dwellings in Myanmar; the pictures indicated how, once damaged, the pillars can lead to the collapse of the house. Recovery is likened to rebuilding the house by repairing the damaged pillars in unison. In addition, culturally relevant pictures were incorporated into five sets of coping cards, each representing core challenges related to the undermining of a specific ADAPT pillar.In terms of the use of concrete representations of distress, we used a picture of a glass filled with varying levels of water to depict higher or lower levels of intensity of emotions. The manual was embellished with metaphors including materials of specific cultural relevance, including stories, idioms and symbols to facilitate comprehension of the content. To ensure the concrete nature of the therapy, we used the story of a generic fictitious character  based on the five ADAPT pillars are incorporated into the treatment to increase the comprehensibility of the content of the therapy.Further information regarding the steps taken to increase the accessibility, uptake, acceptability and hence feasibility of IAT for the Rohingya community in Malaysia.The aim of this report is to detail the rationale and iterative stages of early conceptualisation, development and adaptation of a novel psychotherapy, IAT, specifically designed to address the psychosocial and mental health challenges confronted by refugees. We outline a systematic staged approach in developing and adapting IAT first with West Papuan refugees and then amongst Rohingya refugees in Malaysia. The extensive adaptations and piloting described set the stage for an ongoing pragmatic clinical trial which is in progress in Malaysia.While our approach to adapting IAT is based on a deductive framework drawing on the principles of the ADAPT model, the process of contextualizing and modifying the therapy to each group's culture, history and living context is substantially inductive, although remaining anchored in the informing theoretical framework. Specifically, although grounded in the ADAPT framework, in each setting extensive qualitative assessments are made in collaboration with the refugee community and service agencies, to ensure that the principles applied are localised according to the lived experience of the particular refugee group – as indicated by the procedures followed in modifying the approach amongst the Rohingya. The assumption guiding the approach is that there are universal principles and experiences that bring a level of commonality to the refugee experience worldwide but that these general sources of knowledge only make sense if contextualised within each culture and context.We have attempted to describe IAT in a manner that emphasises its novel elements as well as its overlap with established, evidence-based therapies in the field. This integrative approach – inherent in the naming of the therapy – aims to reflect an effort to harmonise several key elements relevant to the treatment field in this domain of practice. By grounding the method in the ADAPT model, we offer refugees a conceptual structure based on universal principles that appear to make sense when applied to the individual experience of being a refugee, providing a firm anchor point for developing mutual understanding between counsellor and participant. Importantly, the universal understanding offered by the ADAPT model is only useful if it is translated into an analysis of the practical challenges confronting each group based on the particularities of their histories, cultural understandings of mental health, and ongoing living conditions. Ultimately, the definition of problematic areas must be individualised to make sense of the needs of each participant.In summary, IAT aims to integrate four essential goals: to provide a clear but flexible theoretical framework that makes sense of the refugee experience; to translate these principles into the real-life challenges and response patterns relevant to individuals within their culture and context; to use the understanding and insight gained as a motivator for individuals to make adaptive changes; and to provide them with the evidence-based techniques to develop adaptive strategies that are flexible enough to deal with ongoing and future challenges as they evolve.Even though conducted at an individual level, in all phases of therapy, the scope of the therapy explicitly extends beyond the individual to a focus on the family and the wider community; in that sense, by the individual developing adaptive strengths, it is assumed that the benefits will flow on to help strengthen the ADAPT pillars at the systemic level, an intention that is made overt and which resonates with the members of collective societies such as the Rohingya. These core characteristics represent the novel aspects of IAT, offering an alternative approach to psychotherapeutic interventions for refugees. The adoption and wider use of IAT will await the outcome of ongoing trials, including amongst Rohingya refugees, examining the efficacy of the method.


The ongoing tendency to create environmentally friendly building materials is nowadays connected with the use of reactive magnesia-based composites. The aim of the presented research was to develop an ecologically sustainable composite material based on MOC (magnesium oxychloride cement) with excellent mechanical, chemical, and physical properties. The effect of the preparation procedure of MOC pastes doped with graphene nanoplatelets on their fresh and hardened properties was researched. One-step and two-step homogenization techniques were proposed as prospective tools for the production of MOC-based composites of advanced parameters. The conducted experiments and analyses covered X-ray fluorescence, scanning electron microscopy, energy-dispersive spectroscopy, high-resolution transmission electron microscopy, sorption analysis, X-ray diffraction, and optical microscopy. The viscosity of the fresh mixtures was monitored using a rotational viscometer. For the hardened composites, macro- and micro-structural parameters were measured together with the mechanical parameters. These tests were performed after 7 days and 14 days. The use of a carbon-based nanoadditive led to a significant drop in porosity, thus densifying the MOC matrix. Accordingly, the mechanical resistance was greatly improved by graphene nanoplatelets. The two-step homogenization procedure positively affected all researched functional parameters of the developed composites  and can be recommended for the preparation of advanced functional materials reinforced with graphene. Graphene is a carbon-based, two-dimensional nanomaterial and consists of a single monolayer of graphite with a thickness of one atom 0.34 nm). Due to its structure, graphene exhibits extraordinary physical properties such as a high specific surface area, ultrahigh tensile strength and modulus of elasticity, and excellent electrical, optical, and thermal parameters. Graphene nanoplatelets (GNPs) are composed of a few layers of graphene and have a total thickness of less than 100 nm. GNPs inherit many advantages of graphene and, in contrast to it, GNPs can be produced on a large-scale and are cheaper than carbon-based nanotubes and nanofibers ,3. The p4 nm. DueIn recent years, the addition of GNPs to Portland cement-based composites to enhance, in particular, their mechanical, electrical, and durability-related properties was studied intensively. Wang et al.  reportedAs graphene is prone to aggregate in a variety of matrices, it is necessary to achieve the uniform dispersion and distribution of graphene in the mixture to fully manifest its excellent properties . The pro2 emissions generated in cement manufacturing, due to both the combustion of fuels and the decomposition of limestone in the clinker production process. This represents approximately 900 kg of CO2 released per ton of produced cement. To achieve the necessary cement sector decarbonization, high-performance alternative binding materials with low carbon footprints should be researched and put into construction practice [2 from the atmosphere through carbonation process to form carbonates and hydroxycarbonates during their lifespan [2) at a specified ratio [2·MgCl2·8H2O  and 5Mg(OH)2·MgCl2·8H2O (Phase 5) phases can be prepared, which are responsible for the strength and hardness of MOC. At the temperature of ~100 °C, 2Mg(OH)2·MgCl2·4H2O (Phase 2) and 9Mg(OH)2·MgCl2·5H2O (Phase 9) phases are stable [As the requirements of the construction materials grow, the industry of Portland cement (PC) grows with them. The main scope of the development of PC and PC-based concrete is the improvement of its mechanical properties. Previous studies have shown various approaches in this area ,21,22. Hpractice ,24. Magnlifespan ,26. MOC ed ratio . This rae stable . MOC exhe stable ,30.Although Portland cement-based composites with the graphene addition are researched intensively, there are very few published studies dealing with the application of graphene in MOC-based materials. The coupled influence of graphene and diatomite on the properties of MOC-composites was recently reported . The hig2-GNPs aqueous suspension dispersion prior to the preparation of MOC-GNPs fresh mixture, and the additional homogenization of this fresh mixture after the ordinary mixing procedure on the basic structural, microstructural, and mechanical properties of the hardened composites. The obtained results will provide a basic framework for the design of MOC-GNP nanocomposites.Therefore, the main objective of this study is to evaluate comprehensively the influence of the MgCl2·6H2O of p.a. purity  dissolved in tap water. The chemical composition of MgO, analyzed by X-ray fluorescence , was 93.2 wt. % of MgO, 6.2 wt. % of Al2O3, and the residual amounts were only traces of SiO2, CaO, and Cl. Graphene nanoplatelets with a surface area of 300 m2·g−1  were incorporated in 0.5% weight ratio of all dry substances used in the mixture. As shown in The composition of the investigated materials is given in 2 solution using a mechanical rotor-stator homogenizer Ultra-Turrax T-18 . This first mixing was conducted for 5 min at 10,000 rpm. After that, the ordinary mixing procedure based on the technical standard EN 14016-2 [2 solution for MOC-REF, or graphene-MgCl2 solution in the case of MOC-GNPs composites, respectively, were placed into a planetary type mortar mixer (ELE). The mixing started at a low speed regime  for 1 min, followed by high-speed mixing  for 0.5 min. Then, the mixing was stopped to clean the mixer head and the sides of the mixing bowl. After that, mixing continued for another 1 min at high speed followed by casting of MOC-REF and MOC-G samples. The second step of homogenization was applied for MOC-G-H samples only. This composite mix was additionally homogenized using a mechanical homogenizer for another 5 min at 10,000 rpm. The two-step preparation of composites is documented in For the evaluation of homogenization influence on the fresh and hardened paste properties, MOC-graphene composites were prepared with mixing methods based on one-step and two-step homogenization, respectively. Both methods started with the first step of homogenization, where graphene nanoplatelets were dispersed in MgCl 14016-2  was applAll samples were cast into steel molds and were exposed to a laboratory temperature of 23 ± 2 °C and relative humidity of 30 ± 5% for 4 h, followed by demolding and air-curing under the same laboratory conditions for 7 and 14 days, respectively.Morphology of the samples was studied by scanning electron microscopy (SEM), optical microscopy (OM), and high-resolution transmission electron microscopy (HR-TEM). The sample surface was determined by Brunauer, Emmett, and Teller (BET). The phase composition was studied via X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Rotation viscometry was used to measure the change in viscosity of fresh composite mixtures.ρb (kg·m−3), specific density ρs (kg·m−3), and total open porosity Ψ (%) were measured. The microstructure of the formed composites was characterized by mercury porosimetry. Lastly, compressive strength fc (MPa) and flexural strength ff (MPa) were tested. The experimental details can be found in Supporting Information (SI). The expanded combined uncertainty of the applied test methods was as follows: ρb 1.4%, ρs 1.2%, Ψ 2.0%, fc 1.4%, ff 1.4%.Among macrostructural parameters of the hardened composites, bulk density The microstructure of the typical graphene nanoplatelet provided by HR-TEM is shown in MOC-graphene composites and MOC reference without graphene were prepared. The samples were termed as MOC-REF (a reference sample with pure Magnesium Oxychloride Cement), MOC-G (Magnesium Oxychloride Cement with Graphene) and MOC-G-H (Magnesium Oxychloride Cement with Graphene Homogenized by Ultra-Turrax). The photograph of the prepared samples is shown in The fracture surface of the composite samples was studied using optical microscopy. The micrographs see  show the−1, the effect of the addition of graphene on viscosity and thus rheological performance was negligible, which is promising for the design and development of multi-component MOC composites enriched with nanoadditives. It can be expected that the admixing of fillers and mineral admixtures will decrease the viscosity of the composite mixtures. Therefore, the minimal influence of graphene nanoplatelets on the viscosity of examined composites is very beneficial. For lower-velocity gradients, the differences between the viscosity and shear stress of the tested fresh mixtures were well apparent. They can be assigned to the continuous precipitation of MOC constituents. In this case, the lowest shear stress, and thus the dynamic viscosity, exhibited the well homogenized mixture MOC-G-H. This is a positive finding that proves the applicability of the proposed homogenization technique in the production of MOC composites doped with graphene.The rheological curves obtained for fresh composite mixtures are graphed in 3(OH)5Cl·4H2O (ICDD 04-014-8836), which corresponds with the stoichiometry of MOC Phase 5. Graphene was not visible in the diffraction patterns due to its very low content in the composites. Due to that, the diffraction patterns of all three samples were quite similar.The phase composition of the 14-day samples was analyzed using XRD. The obtained diffraction patterns are shown in The microstructure of MOC-REF and prepared MOC composites combined with graphene was analyzed using SEM. The SEM micrographs of the prepared composites are shown in The EDS elemental maps were measured to obtain the chemical composition for comparison of reference and prepared composites. EDS detected the presence of Mg, O, Cl, and C and confirmed the high purity of the prepared samples. Obtained composition was similar for all samples corresponding to the stoichiometry of pure Phase 5. All elemental maps are displayed in 2O, and the lattice vibrations of MgCl2 and Mg(OH)2. The absorption bands between 3700 and 3600 cm−1 are caused due to stretching modes of O-H bonds in the hydroxyl group in Mg(OH)2, while the broad absorption band with maximum at 3375–3346 cm−1 can be assigned to the stretching vibration of O-H bonds in the hydroxyl group in water. The band intensities at 1646, 1608, and 1157 cm−1 are bending vibrations of O-H bonds in the hydroxyl group in Mg(OH)2 [−1, the stretching vibration of Mg-O in MgCl2·8H2O can be found. The series of modes in the range of 1000–400 cm−1 originated from the lattice translation vibrations (Mg-OH) and vibrational vibrations of Mg-O/Mg2+, O/O-Mg-O/O-Mg2+-O bonds [−1 can be contributed by the vibrations of the bonds of Mg-Cl or Mg-O.The collected FT-IR spectra are presented in the form of spectral lines in  Mg(OH)2 . At 1622−1, which can be attributed to the stretching vibration of the C=C bond [−1. This band also partially overlaps with the intensive band of the stretching vibration of Mg-O in MgCl2·8H2O. Based on this phenomenon the peak resolution was found to be at 1611 cm−1 in the case of MOC-G and MOC-G-H samples.The analyzed spectrum of graphene evidences only one weak band appearing at 1586 cmC=C bond ,38,39. IThe macrostructural parameters of the hardened composites are shown in The pore size distribution curves obtained by mercury intrusion porosimetry are given in The microstructural parameters of 14-day cured samples are summarized in The investigated mechanical parameters are presented in The two-set homogenization procedure led to the increased growth of the compressive strength. On the other hand, the improvement of the flexural strength due to the modified homogenization procedure was not great, but still sufficient for the practical use of graphene-reinforced MOC materials in construction practice. Obviously, the two-step homogenization procedure improved the distribution of graphene particles in MOC fresh mixture, which consequently resulted in the upgraded parameters of the hardened composites.For all researched composites, the prolonged curing time significantly increased both observed mechanical parameters. This is in agreement with the findings of other authors, who reported the strength development of MOC mixtures with curing age . This waThe addition of graphene did not increase the viscosity of the fresh mixtures, which is positive for their presumed application in the design and development of the advanced types of multi-component MOC composites for construction applications.Both presented mixing procedures designed for MOC mixtures with graphene enabled the production of materials with decreased porosity and greatly improved mechanical resistance, in comparison with the ordinary MOC paste.The two-step mixing technique even improved the structural and mechanical parameters acquired for MOC-graphene composite homogenized using the one-step technology.The effect of the mixture homogenization procedure in the preparation of magnesium oxychloride cement paste doped with graphene nanoplatelets on its fresh and hardened properties was studied. The addition of graphene and the process of two-step homogenization resulted in the following aspects:This represents very promising results for the future research and prospective application of carbon-based nanoadditives in the production of building materials.


In this work, chemical vapor deposition (CVD)—grown 3D-GrFoam was nitrogen-doped and platinum functionalized using hydrothermal treatment with different reducing agents  hydrate, respectively). X-ray photoelectron spectroscopy (XPS) survey showed that the most electrochemically active nitrogen-doped sample (GrFoam3N) contained 1.8 at % of N, and it exhibited a 172 mV dec−1 Tafel plot associated with the Volmer–Heyrovsky hydrogen evolution (HER) mechanism in 0.1 M KOH. By the hydrothermal process, 0.2 at % of platinum was anchored to the graphene foam surface, and the resultant sample of GrFoamPt yielded a value of 80 mV dec−1 Tafel associated with the Volmer–Tafel HER mechanism. Furthermore, Raman and infrared spectroscopy analysis, as well as scanning electron microscopy (SEM) were carried out to understand the structure of the samples.Three-dimensional graphene foam (3D-GrFoam) is a highly porous structure and sustained lattice formed by graphene layers with sp With the ongoing efforts to transition energy systems, the defining of a new carrier of energy that completely removes carbon from this chain is vital to avoiding the major problems facing the global economy. The transition to clean energy cannot be conceived without involving, to a certain extent, hydrogen, i.e., HNowadays, electrolysis is considered one of the most favorable solutions to producing hydrogen for transport and mobile applications to alleviate the depletion of fossil fuels and maximize the utilization of renewable energy ,2. Compa−), which is formed after the electrochemical decomposition of the alkaline solution. Hydroxide ions are oxidized at the anode forming oxygen gas, and water is reduced at the anode generating hydrogen. During electrochemical water reduction, two electrons are necessary to produce hydrogen gas at the cathode . I. I2 hybrAs shown in As shown in −1, although the D band position was spread between 1345 and 1375 cm−1. The correlation between the data was given by the cluster main axis orientation, whose slope was 0.015 ± 0.002. These features are typically observed in strained multi-layer graphene (or bulk graphite). This is also supported by the ID/IG ratio . Additionally, the cluster slope denoting the correlation between the G and D bands is nearly one order of magnitude higher (−1). This offers the possibility for N doping from urea, either at domain edges  or inside graphene structures . The obtained results are in good correlation with those related regarding the morphology of porous carbon specimens after Ni removal, as well as graphene foam un-doped and doped with nitrogen. Li et al. [−1 (G band) and 1331.8 cm−1 (D band). In the Raman spectra, carbon spherules exhibit D and G bands with nearly identical intensities, although a true de-convolution of the corresponding spectra of un-doped specimens indicate that the intensity ratio ID/IG is preponderantly sub-unitary  associated with multi-layer graphene flakes and the high values  commonly observed in reduced graphene oxide. In c = 1.346 ± 0.018. This is evidence for the reduction reaction occurring on the carbonic spherules which may also provide defect sites for N-doping upon treatment with urea. Since samples with sub-unitary ID/IG values are observed in D/IG) reflects the defective degree of the carbon materials.In ratio in b, with ve higher c, with ae higher d, with we higher a with w i et al.  reported-unitary f, with xistogram f is far −1, 3300 cm−1, and between 2850–2925 cm−1 are associated with O-H, N-H, and -C-H/=C-H stretching vibrations, respectively. The C-O stretching vibration peak positioned at 1603 cm−1 in the GrFoam sample was shifted to 1612 cm−1 in the GrFoamPt sample, which is attributed to the Pt bonding with the porous graphene and carbon spherule substrate. The band from 1719 cm−1 ascribed to the amide C=O stretching vibration is seen in all the nitrogen-doped samples, and this is related with the COOH groups located at the graphene oxide margins [−1, 929 cm−1, 663 cm−1, and 537 cm−1, respectively [−1 and 584 cm−1, respectively, for the GrFoam1NPt sample due to the Pt interaction with the GrFoam1N structure. The FTIR spectra suggested that nitrogen-containing groups were presented after the N-doping process, which is consistent with the XPS studies. margins . The GrFectively ,41. The The structural, compositional and morphological characteristics of the samples suggests the efficient functionalization of using nitrogen and platinum anchored to the pristine GrFoam substrate.−1 in nitrogen saturated 0.1 M KOH  plots recorded with a scan rate of 5 mV s.1 M KOH a, and co−1, 80 mV dec−1, and 100 mV dec−1, respectively  followed by electrochemical reduction and hydrogen molecule formation. For the platinum-functionalized graphene samples, the Tafel slope decreased, and the rate-limiting step for the HER is the Volmer–Tafel mechanism, in which two adsorbed hydrogens recombine and form a molecule of hydrogen. These mechanisms control electron transfer through the electrode and represent the rate-limiting steps for HER [2 nanoflakes) have excellent electrocatalytic activity with a low overpotential of 153 mV at a current density of −10 mA cm⁻² and a small Tafel slope of 58.7 mV dec⁻¹.From ectively b. Moreov for HER ,45. Zeng for HER  reported for HER  reportedIn summary, this paper presents our results in approaching metal-free catalyst synthesis using the hydrothermal nitrogen-doping method of porous graphene obtained by the CVD method, in comparison with platinum trapping on the graphene support.−1 Tafel plot associated with the Volmer–Heyrovsky hydrogen evolution (HER) mechanism in 0.1 M KOH.It was proven that it is possible to use graphene foam (GrFoam) for high corrosion resistance in alkaline environments, an enhanced mass transport (water and gases) flow field, and catalytic support. The replacement of porous metal in electrolysis systems , and the development of lightweight, economical, durable, and good electrochemical activity catalysts for HER are very important. In this paper, it was shown that, through hydrothermal treatment of GrFoam with different quantities of urea combined with ammonia and hydrazine at high temperature and under a nitrogen atmosphere, it was possible to produce nitrogen-doped graphene catalysts for HER. From the plot of the potential vs. the logarithm of current density in absolute values, it can be concluded that the most electrochemical active nitrogen-doped sample was GrFoam3N. This sample contains 1.8 at % of N, and it exhibits a 172 mV decD/IG histograms, whose Lorentz distributions shift to higher values upon hydrothermal treatment with reducing agents in air. As a result, N-doping is promoted on defective C-sites by the presence of exfoliated graphene and the high specific area of graphene oxide spherules. Moreover, platinum deposited by the hydrothermal method on both pristine and nitrogen-doped porous graphene is anchored to both the graphene foam and the carbon sphere surfaces. In conclusion, we may state that the GrFoam complex network produced by CVD can accommodate nitrogen and platinum functional groups for fuel cells and electrolysis applications.Raman imaging data scans indicate that the D and G band positions are highly correlated, such that un-doped and N-doped specimens were distinct. Data analysis offers the possibility to discretize among multi-layer graphene and graphene oxide carbons, which are also self-organized in compacted spherules. The effect of N-doping on graphene foams is reflected in both the cluster relation between the D and G band positions and the I


TAR-DNA-binding protein-43 (TDP-43) is a member of hnRNP family and acts as both RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation in various diseases. Currently, emerging evidence gradually elucidates the crucial role of TDP-43 in human cancers like it is previously widely researched in neurodegeneration diseases. A series of RNA metabolism events, including mRNA alternative splicing, transport, stability, miRNA processing, and ncRNA regulation, are all confirmed to be closely involved in various carcinogenesis and tumor progressions, which are all partially regulated and interacted by TDP-43. Herein we conducted the first overall review about TDP-43 and cancers to systematically summarize the function and precise mechanism of TDP-43 in different human cancers. We hope it would provide basic knowledge and concepts for tumor target therapy and biomarker diagnosis in the future. TAR-DNA-binding protein-43  was first cloned (43 kDa) in 1995, and its name was derived from the characteristics of binding to human immunodeficiency virus type 1 (HIV-1) TAR DNA sequence motifs –7. EmergHuman TDP-43 is located in chromosome 1p36.22, belonging to a member of hnRNP family . As illuMore than 50 disease-associated mutations of TDP-43 gene have been identified in amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD) patients, which are mainly concentrated in the glycine-rich C-terminal region, indicating that the ability of TDP-43 for cooperative assembly on RNA binding sites plays a role in disease mechanisms. TDP-43 mutation (Q331K) resulted in cytosolic mislocalization, impairing the nuclear localization of XRCC4–DNA ligase 4, which contributed to persistent DNA damage accumulation . TDP-43 Generally, TDP-43 is well confirmed by previous studies to mainly regulate RNA metabolism, like biogenesis, processing, decay, and transport, in various diseases. Here we stated these tumor-associated molecular mechanisms with several parts in detail as discussed in the following paragraphs 25 sequence. However, the precise mechanism of TDP-43 and CDK6 mRNA was not elucidated at that time  of TDP-43 revealed a novel mechanism by regulating RNA stability and ribonucleoprotein assembly in certain diseases. For structure basis, α-helical component in the center (residues 320–340) of the C-terminal domain is related to the self-association of the protein and LLPS , 72; anoThe role of TDP-43 in DNA damage and repair could also not be neglected –78. In aBy reviewing all the literature about TDP-43 and cancers, we totally found 11 types of cancers involved. In this part, we will review this topic by cancer type in detail Table 1.Breast cancer is the most and best investigated cancer on TDP-43 function and mechanism. The role of TDP-43 in breast cancer was first mentioned in curcumin therapy research. Investigators found that the anticancer agent curcumin could effectively inhibit breast cancer cell proliferation (cell cycle arrest and apoptosis); further proteomic analysis suggested that TDP-43 was significantly downregulated after curcumin treatment , but theTwo studies suggested that TDP-43 regulated lung cancer progression involving miRNAs and lncRNA. To investigate the mechanism of TDP-43 in regulating lung cancer-associated miRNA biogenesis, Chen et al. used miRNA sequencing after knocking down TDP-43 and found that TDP-43 knockdown affected the expression of many miRNAs and altered the patterns of different isoforms of miRNAs (isomiRs) and miRNA arm selection. In addition, TDP-43 was also confirmed to directly interact with some mature miRNAs like miR-423-3p and miR-500a-3p. Further analysis showed that miR-423-3p was responsible for the cell migration induced by TDP-43, and miR-500a-3p may serve as a prognostic marker of lung cancer . All thevia activating autophagy . Knockdown of TDP-43 significantly inhibited HCC cell proliferation; through mRNA sequencing and bioinformatic sequence analysis, TDP-43 could directly bind to the promoter of miR-520 family to inhibit the expression. In addition, PFKP was further identified as the direct target of the miR-520 family. Consequently, the TDP-43/miR-520s/PFKP regulatory axis was established to explain the HCC glycolysis mechanism . RecentlSimilar to the regulatory role of TDP-43-mediated glycolysis in HCC, TDP-43 was also confirmed to be a novel oncogene promoting melanoma cell proliferation and migration, which was also a poor prognosis indicator for overall survival. For mechanism investigation, TDP-43 regulated the GLUT4 expression in an indirect way; however, the specific mechanism needed further investigation .A preliminary influence test of TDP-43 on cervical cancer was also reported. In HeLa cells, overexpression of TDP-43 caused partially p53-dependent G2/M arrest and p53-independent cell death . AnotherP = 1.4 × 10−20; odds ratio = 2.2), located 25 kb upstream of TDP-43, was associated with susceptibility to Ewing sarcoma. The variant was associated with TDP-43 expression levels  TDP-43-mediated important oncogene or tumor suppressor mRNA splicing and stability regulation, (2) the interaction between TDP-43 and miRNAs (miRNA processing or co-regulation), and (3) regulating downstream targets that interacted with lncRNA or other RBPs. We hope that this conclusion would provide some research experience or any ideas for other researchers who want to investigate this field. However, a small shortcoming is that only some preliminary findings indicate that TDP-43 is rather important in certain tumors, and the precise molecular mechanisms mediated by TDP-43 are still unclear, which need further investigation in the future. Considering the dysregulated expression pattern, it is also promising to find the target drug or translate it into a sensitive and specific biomarker for tumor therapy and diagnosis. To conclude, we hope that this review could provide detailed and systematic concepts and knowledge of cancer-associated TDP-43.XM, YY, and HX performed literature search and reviewed the literature. XM drafted the manuscript. JL, XW, and XL revised and finalized the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (nos. 81802564 and 82103243), the Zhejiang Province Medical and Health Scientific Research Project (2019RC033), the Zhejiang Provincial Natural Science Foundation of China (LY20H160022), and the China Postdoctoral Science Foundation (2020M681885).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The continuance of the COVID-19 pandemic largely depends on the spread of virus-carrying aerosols in ambient air. The mechanism of virus transmission and infection remains under intense investigation. In this study, an evaporation flow model of airborne sputum droplets is proposed which considers the evolution effects of the humidity field under different particle distributions and solid/salt fraction interactions. The incompressible Navier–Stokes equations characterize a stream of airflow jets, and the convection-diffusion-evaporation process is used to account for the inhomogeneous humidity field caused by the respiratory tract. Momentum equations for droplet dynamics which involve the effects of drag, gravity, and Brownian motion on sputum droplets are introduced to quantify the transport of droplets in a humidity field. The Lattice Boltzmann method is used to track the evolution of the aerosol in space and time under different ambient temperature and relative humidity conditions. The results of the simulation demonstrate that airborne humidity accelerates the evaporation rate of droplet, while supersaturated humid air forms a vapor mass in front of the respiratory tract. Despite the short lifespan of this phenomenon, it significantly hinders the evaporation of the droplets. Besides, the droplet vortex dynamics in a humidity field are sensitive to the droplet size. I.The COVID-19 pandemic has attracted scientific attention to the mechanism of the transportation of airflow and the ejection of aerosols from the respiratory tract through coughing, sneezing, and breathing.et al.et al.μm, depending on the mechanism of their generation and their original site. Chao et al.μm when coughing and talking, respectively.et al.μm, where 82% of droplet nuclei were centered in a range of 0.74–2.12 μm.In coughing, the accumulated air is compressed after deep breathing and then expelled rapidly. The exhaled air carries sticky saliva droplets from the lungs, respiratory tract, and trachea. Many studies have focused on the active forms of these clouds to determine the size of the sprayed droplets. For example, Bourouiba et al.μm) has a lower Stokes number, which allows it to float in the ambient air. However, that model ignored gravity, which may limit the effectiveness of its droplet trajectory predictions. Dbouk et al.et al.μm and initial velocities of 21.0, 10.0, and 5.0 m/s traveled 2.35, 1.1, and 0.55 m, respectively. Both the evaporation of the droplet and the exhaled airflow affect the movement of the droplet.Since the beginning of the COVID-19 pandemic, several studies have applied force balance analysis to aerosols in the airflow to explore the threat range of virus-carrying aerosols. Using molecular collision theory, a susceptible-exposed infectious recovered-deceased model for using in large-scale population exposure was proposed by Chaudhuri et al.μm; when the droplet size reaches 540.0 μm, the droplet may be transported to more than 4.0 m. However, this model ignored the temperature effect. Li et al.et al.Computational fluid dynamics has been effectively used to study the flow of aerosols and in relation to different environments.μm) are wrapped in a vapor cloud of saturated humidity and showed various dynamic behaviors. For example, Mahjoub et al.et al.Several modelsThis study proposes an evaporation flow model of airborne sputum droplets containing solid/protein/salt ingredients and presents an efficient and accurate numerical method to simulate the dynamic behaviors of the dispersion and evaporation flow of airborne sputum droplets in a humidity field. This model features an advection-diffusion equation that describes the evolution of the supersaturation field puffed from the respiratory tract. The classic Eulerian–Lagrangian method based on one-way coupled fluid dynamics was used to combine the complex flow processes, including the ejection of an incompressible fluid containing droplets, energy balance, mass transfer, and dynamic transport. Physical parameters, such as ambient temperature and RH, are simulated by the Lattice Boltzmann method. The vortex dynamics of droplets in the humidity field are investigated by integrating the Langevin equation with gravity and drag force. The group of droplets obeying the Rosin–Rammler distribution in humidity field are discussed in detail.II.A.r is ejected with initial horizontal velocity 0u. As shown in fT and dT, respectively. In evaporative flow from sneezing or coughing, aerosols carrying solid/protein/salt components finally settle on the ground or suspend in the air. The gravitational force, the Stokes drag force, and the Brownian force have an effect on the dynamic behavior of droplets.In this study, the streams of humid jets emitted in talking, coughing, and sneezing are simulated. An aerosol with radius B.1.fu (m/s), fρ (kg/m3), and p (Pa) represent the velocity, density and pressure field, respectively, and fμ (Pa·s) is dynamic viscosity coefficient of airflow. The droplets produced in the respiratory tract are carried out by the respiratory airflow, and the evolution of the aerosol radius is significantly affected by the temperature of the airflow surrounding the droplet. The initial temperature of the airflow is close to the body temperature of the human body. The movement of the exhaled airflow into the air is accompanied by the transfer of energy. The energy equation used to describe the temperature change of the airflow can be given asIn order to develop a mathematical model of the droplet dynamics in a turbulent airflow exhaled from the mouth, the incompressible Navier–Stokes equations system is used to model the ambient airflow field.fT (°C) is the temperature field of airflow, pc [J/(kg·°C)] and λ represent the specific heat capacity and the thermal conductivity coefficient, respectively.Here, φ (= RH − 1) is supersaturation field, and dD is the water vapor diffusion coefficient. The fluctuations of supersaturation are produced inside the cloud by the turbulent velocity field acting on the vertical gradient of humidity sustained by temperature.Except the temperature of the airflow, the humidity around the droplet determines the amount of saturated water vapor on the surface of the droplet and affects the evaporation of the droplet. The exhaled airflow is assumed as saturated, or close to saturation.2.a.Va), which is mainly determined by the difference between the amount of saturated steam on the droplet interface (C1 [kg/m3]) and the amount of partial steam in the air (C2 [kg/m3]). The expression is given asVa [kg/(m2·s)] is the amount of the evaporation per unit time and surface area and k (m/s) is the mass transfer coefficient. Water activity is a thermodynamic measure of water, which expressed as the vapor pressure of water in a sample divided by vapor pressure of pure water at a given temperature.The evaporation of droplets is governed by the amount of evaporation of the droplet vapor into the air  living in Aomori Prefecture of Japan, with an average age of 20. For each students, 1.0 ml of saliva was collected into vials using micropipette. Then the saliva samples were dried at 60 °C for 90 h. The weight for different statuses was conducted by electronic scale . The results are shown in C1 on the saliva surface as the following:dT (°C) is droplet surface temperature, vx refers to the mole fraction of evaporated solvent in saliva, and C2 is closely related to the partial water vapor pressure in the air,fT (°C), RH, and k is correlated with the Schmidt number (Sc), Reynold number (Re), and the diffusion coefficient (D [m2/s]) of vapor in the air,dD (m) is the droplet diameter. The mass transfer equation of the droplet can be derived asdm (kg) is the droplet mass, and dA (m2) is the surface area of the droplet. The mass transfer of droplet is mainly reflected in the change of droplet radius. Therefore, the mass of the droplet is divided asUnder the above conditions, the saturation pressure of water is reduced by the nonvolatile components, which affects the evaporation rate of the droplets. Based on Raoult's law, droplet . C2 is cairborne , respectL (J/kg) is the latent heat of the droplet. The convective heat transfer coefficient h [W/(m2·K)] is calculated by a modified Nusselt number asλ is the thermal conductivity coefficient of air. The Spalding heat transfer number (TB) can be calculated bydq (J) is the heat energy transferred to the droplet amd pvC [J/(kg·°C)] is specific heat.The droplet temperature is governed by the thermal balance. By ignoring the radiation heat exchange, the heat exchange between the droplets and air mainly includes the convective heat exchange and the evaporative heat exchange. Therefore, the heat transfer equation can be written as3.−7–10−5 m) suspended in the airflow keep a random irregular Brownian motion, which is the interaction between Brownian particles and the surrounding medium. The Langevin equations are written asxd/dt and dud/dt are the coordinate and velocity change in each discrete time step, respectively, and xd (m) and ud (m/s) represent the Cartesian components of the position and velocity vectors. The first term on the right-hand side of Eq. λ = 6πfRdμ, where dR (m) is the droplet radius and fμ (Pa·s) is the viscosity.The small aerosols ⟩ = 0) and a second-order moment of D (⟨ζ(t), ζ(t′)⟩= Dδ(t − t′)).D is the strength of the fluctuating force, which is obtained from the Einstein relation, D = BTdλK, where BK = 1.38 × 10−23 J/K is the Boltzmann constant.The second term in the right-hand side of Eq. dm (kg), dV (m3)d, R (m)d, ρ (kg/m3), and ud (m/s) are the mass, volume, radius, density, and velocity of the saliva droplets, respectively. fρ (kg/m3) and uf (m/s) are the density and velocity of airflow, respectively. DC is the drag coefficient which can be calculated by a function of Reynold number asThe Langevin equations mentioned above only contain the force which expresses the Brownian motion of the tiny droplet. To involve the effect of other forces, the Langevin equations can be further written asC.The present work refers to fluid flow, heat transfer, droplet movement and droplet evaporation. To further improve the computational accuracy, an effective method based on OpenMP technology has been employed in this section. A comparison between the current model and literature models can be found in 1.αf and eqαf are the distribution function and the equilibrium distribution function, respectively. τ is the single relaxation parameter, Δt is the time interval, eα and αω represent the particle velocity and the weights coefficient, respectively. For D3Q15 model, αω and c2s are set as ω0 = 16/72, ω1–6 = 8/72, ω7–14 = 1/72, and c2s = c2/3, respectively. The particle velocity of D3Q15 is given asc = Δx/Δt = 1 is the lattice velocity and Δx is the lattice spacing. The kinematic viscosity υ, which is related to the relaxation time τ,Unlike the traditional CFD numerical methods, the lattice Boltzmann method (LBM) has the characteristic of the mesoscopic model between the microscopic molecular dynamics model and the macroscopic continuous model. LBM is used to solve Eq. ρ and velocity uf are computed by the density distribution function αf asThe fluid density 2.3, and the grid is set to 800 × 150 × 150) improves the calculation efficiency. The center position of the lips is . A ghost cell approach is used to impose the boundary conditions. The inlet velocity is set to the Dirichlet boundary condition, and the velocity is only imposed on the lips. After completing an exhalation, the inlet boundary velocity is changed to zero. The Neumann outflow boundary conditions are used for the rest boundaries.In this study, a person with a height of 1.7 m is considered to stand in an outdoor environment, and breathe, cough, or sneeze droplets that is approximately 36.0 °C. The oral cavity is 1.55 m above the ground . The exhfT  = 30.0 °C and RH = 0.5 . The velocity of the mouth in 0.16 sxu = 5.5 m/s. The kinematic viscosity coefficient of the air is set to the order of 10−6 m2/s. The resulting Reynolds number  is about 6000. The initial droplet size distribution is based on the Rosin–Rammler distribution law,The droplet is initially at rest and randomly distributed over a 4.0 × 4.0 cm mouth plane. The droplet and the turbulent cloud are injected at the same velocity from the mouth into the computational domain with an airborne temperature The algorithm is based on the Lattice Boltzmann method for the discretization of the Navier–Stokes equations Eqs.  on EulerIII.A.et al.μm) to compare their evaporation time in a moderate temperature environment. The ambient air temperature and the initial droplet temperature are 30.0 °C and 36.0 °C, respectively, and RH is 0.84. In In this section, the existing single pure droplet evaporation is compared with the numerical results of Li B.t = 0.496 s, only a slight vapor concentration gradient can be observed. Due to the exhalation of supersaturated air and the evaporation of droplets, respiratory droplets are dispersed in an inhomogeneous humidity field, particularly in the area near the opening respiratory tract (such as the lips and nostrils). Therefore, the RH and the humidity field have significant effects on the characteristics of droplet evaporation, droplet dispersion trajectories, and viral viability.The above validation is conducted on pure water in a coordinated environment (stable RH), which ignores the effect of the inhomogeneous humidity field.μm. The evaporation time before the droplet transforms into an aerosol increases with RH. By the inspection, the evaporation time for a droplet at RH = 0.9 is approximately 35.0 s, which is five times longer than that at RH = 0.5. The greater the air humidity, the greater amount of airborne saturated water vapor, which makes the droplets evaporate quickly. Under a lower RH, a small droplet evaporates rapidly into smaller residual nuclei, which remains suspending for a long time. Therefore, pathogens within the nuclei of these droplets may present a greater long-range transmission threat than the droplets in high humidity.RH refers to the percentage of water vapor pressure in the ambient air to the saturated water vapor pressure at the same temperature. The evaporation rate for airborne sputum droplets with a solid fraction at different RH (from 0.1 to 0.9) is compared in μm at most, which is almost twice the time's value of that at a humidity of 0.1 (16.3 μm). The reason is that these droplets contain a variety of complex and nonvolatile soluble components, such as salt and protein, which decrease the activity of water. The mole fraction of the solvent in saliva decreases with the decreasing in moisture. Conversely, the proportion of droplet vapor evaporated into the air decreases with the increasing mole fraction of the solute. The presence of solid components in the aerosol increases the latency of the virus immersed in droplets.RH not only influences the rate of droplet evaporation but also determines the equilibrium state of droplet evaporation. When the droplet evaporates to a certain extent, an inflection point appears, and droplet diameter maintains an equilibrium stage . SimilarViolent expiratory events, such as coughing and sneezing, generate turbulent jets.Ddifferent is the difference between the droplet diameter under the humidity field and the non-humidity field at the same time. Generally, the higher the RH is the smaller influence on the humidity field applied on droplet evaporation. At the beginning of the exhalation (within 0.16 s), Ddifferent is 1.6 μm at RH = 0.1. At this time, the diameter of the droplet under the non-humidity field only evaporates within 2.0 μm. It indicates that the droplet is greatly protected compared to the droplet in a non-humidity field. From the peak value of Ddifferent at different levels of humidity, the lower the environmental humidity could result the higher the degree of protection of the droplets. After an exhalation is complete, the influence of the humidity field on the evaporation of droplets gradually decreases, but it still continues. Ddifferent gradually expands. The maximum value of Ddifferent nearly reaches 5.0 μm for RH = 0.1. With the gradual dissipation of the humidity field, the influence of humidity field on droplet evaporation is disappeared, and the droplet is in the same equilibrium state.The humidity field, which originates from the turbulent velocity field, and acts on the vertical gradient of humidity, is sustained by temperature. The existence of the humidity field depends on the velocity field. It can be observed in The influence of the humidity field on the dynamic trajectory of droplets can be observed in C.μm, 0.5, and 5.5 m/s, respectively. The ambient air temperature accelerates the evaporation of droplets which is observed in t = 7.5 s for fT = 40.0 °C, or t = 16.5 s for fT = 10.0 °C. The combination of Ambient air temperature is another important factor, which affects the evaporation and flow of aerosols. Ambient air temperature determines the saturation of water vapor pressure on the surface of the droplet, and the amount of heat exchange between the dispersed and continuous phase.t < 0.16 s), the droplets are wrapped in turbulent clouds, and the droplets are almost unaffected. As the exhalation is completed, the droplet gradually evaporates. Both the convective heat exchange based on the difference between droplet temperature and air temperature, and the evaporative heat exchange caused by droplet evaporation, takes away the internal energy. Based on that, the temperature gradually drops. Then, the amount of the droplet evaporates into the air, and tends to be stable, as the result, the temperature is equilibrated. Finally, due to the presence of solid components, the droplet evaporates slowly and transforms into aerosols which suspended in the air. The temperature of the aerosols gradually becomes the same as that of the ambient air.The evolution of droplet temperature with different air temperatures during evaporation is shown in D.1.q is an exponential factor that represents the width of the particle diameter distribution. Saliva droplets are ejected from the mouth in different sizes.μm, respectively) on the humidity field during the entire sneezing cycle from mouth to floor. μm, respectively). The total number of ejected saliva is 1500 and obeys the Rosin–Rammler distribution. Each droplet is composed of 99.2379% water and 0.7621% salt. The outdoor ambient temperature, pressure, and relative humidity are 30.0 °C, 1.0 atm, and 0.5, respectively. The mouth temperature and the initial droplet temperature are both 36.0 °C. In the initial process of exhalation (0–0.16 s), the droplets ejected from the lips move almost linearly along the initial velocity under the effect of the inertia force and the drag force .A key feature of the present simulation is the coupling of transport phenomena, evaporation flow, and droplet dynamics. To test the influence of the evaporated droplets on sedimentation distance in humidity, a comparative study was conducted on the ejection of seven droplets with initial diameters of 20.0–140.0 μm), medium  droplets rebound to the original height after settling for a period  wrapped in a humidity field, the evaporation does not significantly change the mass before it settles. After the inertial force is exerted to its extreme , which can be considered the buffer time for evaporation (shrinking the droplet diameter). Therefore, this is the root cause of their airborne suspended [To explain the rebounding phenomenon, the dynamic trajectory of droplet transport near the humidity field is presented in  extreme , the drouspended . These rIV.(1)The newly proposed physical and numerical model show good accuracy compared with existing models of airborne sputum droplets systems.(2)μm) evaporated at different humidity values (0.1 and 0.9), the final (equilibrium) diameter differed  and the time consumption is 8 times difference . However, the difference in droplet diameter can reach 5.0 μm with RH = 0.1 and the size distribution is nearly the same within 0.16 s of exhalation.It is found that the humidity field generated from the respiratory tract plays a very important role in the evaporation and transport of droplets. With droplets (80.0 (3)μm) that evaporate at different temperatures (10.0 °C and 40.0 °C), the time consumptions of 7.5 and 16.5 s, respectively.Increasing airborne temperatures can accelerate the evaporation and the salt content and relative humidity parameter jointly define the equilibrium diameter of the aerosol. For droplets of the same size (80.0 (4)μm) fall into the rotation of the vortex and rebound backward, which is the buffer time for evaporation (shrinking droplet diameter). This leads to the suspension of more droplets in the environment. Small droplets (20.0 μm) are suspended in a higher position under the rotation of the vortex, which penetrates the respiratory tract more easily.Droplets of the same diameter have different dynamics at the front end of the vortex and the back end of the jet due to the different effects of different values of airborne humidity. Under the accelerated evaporation of the humidity (with a shrinking droplet diameter), light droplets are propelled by the tailing jet. Vortex dynamics of droplets in a humidity field is sensitive to the size parameter, while small and medium-sized droplets (20.0–80.0 An evaporation flow model of airborne sputum droplets that considers the humidity field evolution and solid fraction interactions has been proposed in this study. This model features an advection-diffusion equation that describes the evolution of a supersaturation field. The numerical model has been applied to reveal the mechanism of saliva particles transport in a humidity field.supplementary material for detailed data that supports the findings of humidity field evolution and droplets distributions in this study.See the


Monolayer graphene is now produced at significant yields, by liquid phase exfoliation of graphites in solvents. This has increased the interest in molecular simulation studies to give new insights in the field. We use decoupling simulations to compute the exfoliation free energy of graphenes in a liquid environment. Starting from a bilayer graphene configuration, we decouple the Van der Waals interactions of a graphene monolayer in the presence of saline water. Then, we introduce the monolayer back into water by coupling its interactions with water molecules and ions. A different approach to compute the graphene exfoliation free energy is to use umbrella sampling. We apply umbrella sampling after pulling the graphene monolayer on the shear direction up to a distance from a bilayer. We show that the decoupling and umbrella methods give highly consistent free energy results for three bilayer graphene samples with different size. This strongly suggests that the systems in both methods remain closely in equilibrium as we move between the states before and after the exfoliation. Therefore, the amount of nonequilibrium work needed to peel the two layers apart is minimized efficiently. Graphenes are two-dimensional, single-layer carbon nanosheets with unprecedented physical, mechanical, optical and electronic properties ,2,3,4. TF using thermodynamic integration [The energy required to exfoliate graphene is balanced by the solvent-graphene interactions . Solvente states . If the e states ,24. The egration ,26,27. Tegration ,29.We may configure various paths to transform state A into state B ,31. A com 0 to 1 ,33,34. I−(FB−FC) ,37,38,39In a previous work, we employed one method to compute the exfoliation free energy of graphenes . In brieIn this work, we compute the exfoliation free energy of graphenes using decoupling molecular simulations. The simulations are performed in two stages. In the first stage, we decouple the Van der Waals interactions of a single layer starting from a bilayer graphene configuration, in the presence of saline water. In the second stage we decouple the interactions of the same layer starting from a single layer configuration. The exfoliation free energy is computed by subtracting the free energy differences between the two stages. We consider three bilayer graphene samples with small, medium and large size. Then, we compare the free energy estimates of the decoupling simulations with those of the umbrella sampling in which, the same graphene nanosheets dissociate on the shear direction in respect to the bilayer plane.H is parameterized Hamiltonian, and i and j, the Solvation free energies were computed by simulation by decoupling a nanoparticle from the solvent by thermodynamic integration, using the idendity,particle ,44. The e solute ,45,46.http://chembytes.wikidot.com/buildcstruct, accessed on 28 July 2021) [To configure the bilayer graphenes we considered two copies of a single layer graphene. The single layers were all-carbon sheets, having a honeycomb pattern of carbons and peripheral hydrogens. The layers were planar and square. We generated the coordinate files of the graphene layers using the BuildCstruct script (ly 2021) . We buil carbons ,49,50,51 carbons . All simWe placed the bilayer graphene at the center of a cubic box. We set the nearest edge of the cube at 1.5 nm from the outermost atom of the bilayer. We set the cut off radius to 1.4 nm to be consistent with the minimum image convention. We used periodic boundary conditions in all directions. We solvated the simulation box with simple point charge (SPC) water and we added 100 mM NaCl. Ions were interacting fully with the SPC molecules. They were not interacting electrostatically with the bilayer, because the graphenes were uncharged. Complementary, we performed equivalent simulations for single layer graphene samples with small, medium and large size. We followed the same simulation protocol as for the bilayer graphenes, only that we used a single layer instead of two. The dimensions of the simulation cubes for all the studied systems and the number of molecules described therein, are listed in Before the decoupling simulations, the system energy was relaxed using a steepest descent minimization, followed by an equilibration in the NPT ensemble over 1 ns. We used the Berendsen coupling to regulate the temperature at 310 K and the pressure at 1 bar. The final configuration of the last NPT run, was used as starting configuration for the decoupling simulations. The bilayer graphene and the solvent (water and ions) were coupled to separate coupling paths. We used the Nose-Hoover method for the temperature coupling and the Parinello-Rahman for the pressure. We labeled the two graphene layers using a different index. One layer served as an immobile reference on which, we applied position restraints on the atoms. The other layer was interacting with the reference layer and the ambient molecules on the basis of Equation . We used) method .We considered a two-stage process to compute the exfoliation free energy of graphenes. First we deleted a single graphene sheet from the bilayer configuration, then we solvated the graphene sheet back into the solvent. The free energy difference on the first stage was computed by the decoupling simulations of bilayer graphene samples. Likewise, the free energy difference on the second stage was computed by the decoupling simulations of single layer graphenes. The exfoliation free energy was estimated by subtracting the free energy difference on the second stage from that on the first stage.A different technique to compute the exfoliation free energy of bilayer graphenes is to use umbrella sampling simulations. The umbrella sampling method was discussed in detail in a previous work . There, In Equation . At smalEquation , which mIn The exfoliation free energy of the bilayer graphenes is given by the difference between the relative energies in the two panels in For the sake of comparison, we plot the exfoliation free energies of the bilayer graphenes computed with umbrella sampling simulations, in the right-hand panel of Free energy calculations are independent of the simulation protocol that is used. However, the level of precision does depend very much on the choice of the transformation path ,55. DiffApart from the solvent phase perturbations, discrepancies of the free energy are often attributed to the statistical variance of the molecular simulations. We can see in d system ,56. The The availability of high-yield exfoliation methods to produce isolated, unoxidized and defect-free graphene has increased the interest in fundamental studies on the exfoliation processes by molecular simulations. We compute the liquid-phase exfoliation free energy of three graphene layers with different sizes using two simulation protocols, namely decoupling molecular dynamics and umbrella sampling. Using the two simulations, we estimate very similar free energies regardless of the size of the layers. This reflects the thermodynamic consistency of the methodologies and confirms that we designed the corresponding exfoliation paths to be equally reversible. The modeled systems, containing graphenes and water and ions, are reasonably simple, to be able to obtain good statistical sampling, allowing us to realize a lower bound on the amount of the sampling necessary to simulate more complex structures like functionalized graphenes and other 2D layered materials and metal organic nanosheets.


Actin plays critical roles in various cellular functions, including cell morphogenesis, differentiation, and movement. The assembly of actin monomers into double-helical filaments is regulated in surrounding microenvironments. Graphene is an attractive nanomaterial that has been used in various biomaterial applications, such as drug delivery cargo and scaffold for cells, due to its unique physical and chemical properties. Although several studies have shown the potential effects of graphene on actin at the cellular level, the direct influence of graphene on actin filament dynamics has not been studied. Here, we investigate the effects of graphene on actin assembly kinetics using spectroscopy and total internal reflection fluorescence microscopy. We demonstrate that graphene enhances the rates of actin filament growth in a concentration-dependent manner. Furthermore, cell morphology and spreading are modulated in mouse embryo fibroblast NIH-3T3 cultured on a graphene surface without significantly affecting cell viability. Taken together, these results suggest that graphene may have a direct impact on actin cytoskeleton remodeling. Actin is an essential cytoskeletal protein that promotes the reorganization of cellular architectures, thereby enabling cell morphogenesis, migration, and differentiation ,2,3. Act2 hybridized carbon nanomaterial that has served as a promising biomaterial due to its unique structural, mechanical, thermal, and electrical properties [Graphene is a single layer of spoperties ,20,21,22operties ,24,25. Toperties , biosensoperties , cancer operties , and scaoperties . IncreasSeveral studies have shown that graphene can alter the actin cytoskeleton at the cellular level indirectly through triggering the signaling pathway , produciIn this study, we investigate how graphene modulates actin filament assembly kinetics utilizing total internal reflection fluorescence (TIRF) microscopy imaging and bulk pyrene fluorescence assay. We hypothesize that the non-covalent interaction between actin and graphene may have a direct impact on actin filament assembly. We demonstrate that both pure graphene flakes and graphene surface enhance the average growth rates of individual actin filaments in a concentration-dependent manner. Furthermore, we demonstrate mouse embryo fibroblast NIH-3T3 cells seeded on the graphene surface exhibit stretched cell peripheral regions without incurring cytotoxicity, indicating the hydrophobicity of the graphene surface may modulate cellular morphology. Taken together, our study suggests that graphene can directly modulate actin assembly kinetics, thereby potentially modulating the actin cytoskeleton remodeling in cells.aLvg = 4.04 μm) where the filament length peaked among the range of graphene flake concentrations. At 10 μg/mL graphene flakes, similar lengths of actin filaments compared to controls were observed (aLvg = 3.02 μm), and 20 μg/mL graphene flakes reduced the filament lengths by 15% compared to controls. Next, we conducted bulk kinetic assays using pyrene-labeled actin to determine the effects of graphene flakes on actin polymerization . We polymerized actin filaments  in the absence (control) or presence of graphene flakes (0.5–20 μg/mL). The presence of graphene flakes rendered faster actin filament elongation . WithoutActin assembly dynamics are controlled by various physiological factors ,37,38. OThe observed reduction in actin polymerization at higher concentration of graphene flakes (20 µg/mL) can be explained by the location of two adjacent graphene flakes. The excluded area of two-dimensional materials depends on the relative angle between two particles . The excWe further investigated the assembly of actin on a graphene surface. We used a graphene layer-transferred flow cell to allow consistent interactions between actin monomers and graphene . Interestingly, the graphene surface significantly enhanced the rates of actin filament elongation (16.62 ± 2.05 nm/s), approximately a 45% increase compared to those of the control samples .Self-assembly of peptides and proteins into specific organized structures is joined by non-covalent bonds . Self-asWe further evaluated the effects of graphene on cytotoxicity of mouse embryo fibroblast NIH-3T3 cells, which are widely used to determine the effects of materials on cellular behaviors ,48. NIH-Next, we investigated how graphene affects cell morphology and spreading by visualizing the actin cytoskeleton inside NIH-3T3 cells with optical and confocal microscopy . OpticalCellular adhesion and spreading can be altered by surface properties, such as topography and wettability (hydrophobicity and hydrophilicity) ,56. Lee 2, 1 mM NaN3, 0.2 mM ATP, 0.5 mM DTT, pH 8.0) as described in [2+-actin monomers were converted into Mg2+-actin monomers by the addition of 0.2 mM EGTA and MgCl2 with the concentration of actin plus 10 μM for 5 min, then 1/10th volume of 10× polymerization buffer  was added and incubated at room temperature (T ~ 22 °C) for 1 h as described in [Actin was purified from rabbit skeletal muscle acetone powder  and gel-filtered over Sephacryl S-300 equilibrated in buffer A . Graphene flakes were dissolved in ddH2O and vortexed for 30 s before use for in vitro actin polymerization or dissolved in DMEM media for the cell experiment. A pristine graphene sheet (10 mm × 20 mm) was transferred on a 22 mm × 40 mm coverslip. Chemical vapor deposition (CVD) graphene grown on copper foil from Grolltex  was used. CVD grown monolayer graphene was wet transferred [2 and 10 % H2) ambient at 400 °C for 3 h to remove the contaminants on the graphene film.Graphene flakes were purchased from Alfa Aesar Co., Inc.   for 1 h at room temperature. F-actin samples were diluted in optical imaging buffer  [v/v poly-L-lysine , which produces a weak electrostatic force to adhere biopolymers to glass surfaces [L) were analyzed using ImageJ, Persistence [For steady-state imaging, actin monomers  were polymerized by the addition of KMI buffer in the presence of graphene flakes (dissolved in ddHoxidase) ,66. Actisistence , and Ori2+-bound pyrene labeled G-actin was exchanged to Mg2+ as previously described in [2O, dilution factor ×100) were then added to Mg2+-G-actin. In total, 1/10th volume of 10× KMI buffer was rapidly added to pyrene actin (5 µM) to start actin polymerization. Pyrene fluorescence was monitored at 407 nm every 10 s over 2 h in a 96-well fluorescence plate reader  with 360 nm excitation. Since the graphene surface layer cannot be directly transferred into a 96-well plate, it was not possible to observe pyrene–actin polymerization on the graphene-transferred surface.Pyrene actin (>99% purity) was purchased from Cytoskeleton Inc.  and mixed with unlabeled actin monomers to make 20% labeled pyrene actin. Caribed in . Graphen2O. Two functionalization solutions were prepared by using an 80% ethanol and 1% 1 M HCl solution. In total, 1 mg/mL solutions of mPEG-silane  and biotin-PEG-silane  were prepared in 80% ethanol. The solutions were mixed at a ratio of 1:500 of biotin-PEG-silane to mPEG-silane. Coverslips were incubated overnight at 60 °C in a humid chamber, rinsed with warm water, and dried before using. Then, a flow cell chamber was constructed as described in [w/v) fatty-free BSA solution containing 1% streptavidin (in 1X KMI buffer) was injected into the flow cell chamber to block unnecessary binding. Images of polymerizing actin (18–20% Alexa-labeled) were taken every five seconds using a Nikon Eclipse Ti TIRF microscope equipped with a Hamamatsu Orca-Flash 4.0 Digital Camera C13440, 100× oil immersion objective , and Nikon LU-N4 laser. Nikon Imaging Software (NIS) Elements (ver. 5.02) was used to capture images (pixel size = 0.07 μm/pixel).Functionalized coverslips were prepared using a modified protocol based on Winterhoff et al. ,69. BrieFrom the stacks of images of polymerizing actin filaments, we obtained kymographs that showed the changes in fluorescence intensity of the actin filament backbone over the course of time using ImageJ software. We calculated the actin filament growth rates by plotting the time frame versus the elongated filament length, where the slope yields the elongation rate of individual actin filaments ,69.N-hydroxysuccinimide ester (PNHS) dissolved in dimethylformaide (DMF) for 24 h since biotin-PEG was not able to anchor onto the graphene surface due to its hydrophobicity. PNHS can be used as a linker of biomolecules and graphene as the pyrene groups interact with the graphene surface via π-π stacking while the succinimidyl ester groups react with amines of biomolecules [2O thoroughly, followed by incubation with the biotin-PEG-silane/mPEG-silane solution (the ratio of biotin-PEG-siline to mPEG-silane 1:500) overnight at 60 °C in a humid chamber, rinsed with warm water, and dried before using.A graphene layer-transferred coverslip was functionalized by pyrenebutyric acid olecules ,71. The olecules . Functiov/v) Fetal Calf Serum (FCS) and 1% penicillin/streptomycin in a 5% CO2 incubator at 37 °C. NIH-3T3 cells were seeded in a 6-well culture plate or 96-well culture plate for 24 h. Then, graphene flakes in DMEM containing 10% FCS and 1% P/S were treated into cells and incubated up to 48 h.Mouse embryo fibroblast NIH-3T3 cells were purchased from American Type Culture Collection . NIH-3T3 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10%   were supplemented, and cells were incubated for 2 more hours. For the cell viability assay on the graphene surface, cells were seeded on graphene layer-transferred coverslips or poly-L-lysine-coated coverslips (0.01% v/v poly-L-lysine) as a control in 6-well plates at a density of 1 × 105 cells/well, with a total volume of 2000 μL. After 24 h and 48 h, 200 μL of WST-1 reagents (10:1)  were supplemented, and cells were incubated for 2 more hours. Final absorbance of the samples against a background control  was measured at 450 nm and 630 nm using a SpectraMax i3x .Cells were seeded in 96-well plates  at a density of 5 × 105 cells/well onto coverslips coated with poly-L-lysine (0.01% v/v) in a 6-well cell culture plate. After 24 h, cells were treated with graphene flakes (0.5–20 μg/mL) for 24–48 h. Cells were also seeded at the same density onto graphene-layer transferred coverslips and incubated for 24 h. Bright field microscopy images of cells were obtained using TS2 inverted microscopy  at 24 h and 48 h after treatment. Prior to obtaining fluorescence microscopy images, cells were fixed with 4% paraformaldehyde for 10 min. The fixed cells were then permeabilized for 5 min with 0.1% Triton X-100 in PBS. Coverslips were rinsed with PBS and incubated for 30 min with Acti-stain 488 Phalloidin . Following a PBS wash, the coverslips were incubated for 5 min with DAPI  for counterstaining. Fluorescent images were collected with a BZ-X800 confocal microscope . To quantify the morphology of stretched cells, the aspect ratios (major axis/minor axis) of cells were measured using the ImageJ program [Cells were seeded at a density of 1 × 10 program .p-value): n.s., not significant (p > 0.05); *, p < 0.05; **, p < 0.01; ***, p < 0.001.Statistical significance of the numbers of filaments per bundle, bundle persistence lengths, and bundle diameters was determined using OriginLab ver. 8.5 software by conducting multiple analysis of variance (ANOVA) with post-hoc Tukey’s test. Notation for probability (Here, we report the effects of graphene flakes and a graphene surface on actin filament assembly kinetics and NIH-3T3 fibroblast cell spreading as well as morphology. Direct visualization of individual actin filament assembly in real-time demonstrates that both graphene flakes and a graphene surface significantly enhance the rates of actin filament elongation. Cell culture experiment results show that graphene flake uptake does not incur cytotoxicity. Further, interactions with a graphene surface lead to changes in NIH-3T3 cell spreading and stretched cell morphology, which may be related to the enhanced actin filament assembly kinetics. Our work suggests that interaction/interface with graphene may have a direct impact on the actin cytoskeleton remodeling at the molecular level, possibly modulating cell motility and physiology.