TERT, TERC, PARN, RTEL1), which are also found in about 10–20% of cases of sporadic IPF. In addition to the Mendelian forms, mutations in the genes encoding for the surfactant proteins  and polymorphisms of genes for the mucin MUC5B and the Toll-interacting protein TOLLIP are other pathways favoring the fibrogenesis that have been thoroughly explored. Moreover, great attention has been paid to the main epigenetic alterations  that are emerging to play a role in fibrogenesis. Finally, a gaze on the shared mechanisms between cancer and fibrogenesis, and future perspectives on the genetics of pulmonary fibrosis have been analyzed.Idiopathic pulmonary fibrosis (IPF) is a rare disease of the lung with a largely unknown etiology and a poor prognosis. Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to specific genetic mutations. There is little evidence of the possible role of genetics in the etiology of sporadic IPF. We carried out a non-systematic, narrative literature review aimed at describing the main known genetic and epigenetic mechanisms that are involved in the pathogenesis and prognosis of IPF and FPF. In this review, we highlighted the mutations in classical genes associated with FPF, including those encoding for telomerases ( Idiopathic pulmonary fibrosis (IPF) is a rare, chronic, fibrosing and progressive disease limited to the lung with a largely unknown etiology and a poor prognosis. IPF is associated with a characteristically defined radiological and/or histological usual interstitial pneumonia (UIP) pattern. IPF is characterized by the progressive replacement of lung tissue with fibrotic-scar tissue due to the excessive release of collagen by mesenchymal cells, the myofibroblasts. This process changes the architecture and function of the organ over time and, in the absence of antifibrotic therapy, may lead to death within 3–5 years after diagnosis. IPF is a disease of the elderly, with a mean age of onset of 65 years .IPF is characterized by the presence of progressively worsening dyspnea. Cough and sputum are frequently associated symptoms, especially in more severe patients.According to international guidelines, the diagnosis requires the exclusion of secondary causes of pulmonary fibrosis  and the execution of a high-resolution computed tomography (HRCT) of the chest. Finding a definite usual interstitial pneumonia (UIP) radiological pattern is sufficient to diagnose IPF after the exclusion of any other causes of lung disease. Patients who have a probable UIP pattern on HRCT can receive a diagnosis of IPF after a multidisciplinary discussion (MDD) by at least a pulmonologist, a radiologist and a pathologist. Lung biopsy is today adopted only in limited complex cases, particularly when an IPF diagnosis is strongly suspected but the radiological pattern is indeterminate for UIP or suggestive for other interstitial lung diseases.Bronchoalveolar lavage (BAL) is a bronchoscopic sampling procedure useful in the diagnostic work-up of idiopathic pulmonary fibrosis that helps rule out other fibrosing interstitial diseases that can enter into differential diagnosis with IPF. Although there are no specific cellular patterns for IPF, BAL could help in the diagnosis of other interstitial lung diseases (ILD) such as sarcoidosis, eosinophilic pneumonia, chronic extrinsic allergic alveolitis or nonspecific interstitial pneumonitis ,3.To date, no pharmacological therapy can stop or reverse the fibrosing process. Two drugs, nintedanib and pirfenidone, have been approved for the treatment of the disease, since in clinical trials and observational studies they have been shown to slow down the progression of the disease, without, however, being able to stop or cure it ,5. SeverDespite several advances in understanding the pathogenetic mechanisms of the disease, the origin of IPF remains largely unknown. The main risk factors include cigarette smoking, lung infections , exposure to pneumotoxic inhalants, gastroesophageal reflux, elderly age, diabetes mellitus and genetic predisposition .Intriguingly, forms of familial pulmonary fibrosis (FPF) have long been known and linked to mutations in specific genes . FPF is TERT, TERC, PARN, RTEL1) [TERC and TERT mutations, respectively). The involvement of bone marrow function in the pulmonary fibrosis (PF) phenotype is also reported for patients with ZCCHC8 and RPA1 variants. The familiar forms of PF include ILD2 (OMIM #178500), a disease related to SFTPA2 mutations and characterized by pulmonary fibrosis, interstitial pneumonia and lung cancer.Genes associated with FPF include those encoding for telomerases, responsible for the regulation of telomeres length and therefore involved in cellular aging  ,9,10. TwFinally, pulmonary fibrosis can also be part of the POIKTMP syndrome . FPF can manifest either as IPF, but also as connective tissue disease-interstitial lung disease (CTD-ILD) or unclassifiable interstitial lung disease (U-ILD) ,11.On the other hand, there is little evidence of the possible role of genetics in the etiology of sporadic IPF, although mutations in FPF-causing genes are also found in about 10–20% of sporadic IPF cases.Even if the genetic predisposition to PF is known, the molecular diagnosis of familial cases is probably underestimated, and this could be related to the incomplete penetrance of the disease or the lack of information from the patient’s pedigree. In order to recognize the familial cases, it is important to identify the risk in family members not only for PF but also for possible related conditions, mainly lung cancer and bone marrow failures. In addition to the Mendelian forms, several studies support the existence of a genetic predisposition to pulmonary fibrosis, which is expressed as a complex trait in which low-penetrance genes and environmental factors play a role. In particular, the involvement, even in sporadic forms, of genes related to the production of surfactant proteins, which would alter the functionality of the pulmonary alveoli, or of genes responsible for an increased chronic secretion of mucus, is highlighted .Finally, epigenetic alterations seem to play a role in fibrogenesis. Several studies consider cellular aging as an endogenous causative factor of IPF, which favors the development of genomic instability, the establishment of epigenetic alterations, the shortening of telomeres and cellular senescence, thus laying the foundations for the development of fibrosis .Overall, heterogeneous genetic variants could contribute to the development of an altered broncho-pulmonary tissue, which would become more susceptible to recurrent micro-lesions from various potential environmental factors.In this study, a state-of-the-art review of the genetic and epigenetic bases already explored in IPF and FPF will be presented, along with an overview of their possible implications for therapy. For this purpose, a non-systematic, narrative literature review was conducted. The search engine PubMed was adopted to retrieve the most relevant articles on these topics from international scientific journals.PF can have a strong genetic component in 10–20% of cases, as previously described, or gene variants can modify the risk so that it is affected together with the influence of the environment. In addition, genetic factors might also influence the onset of the disease  Figure .TERT, TERC, PARN and RTEL1, which regulate the telomere length, thus resulting in shortened telomeres, have a recognized causative role in IPF and FPF [Particularly, mutations in the genes of the telomerases, such as  and FPF .SFTPC, SFTPA1, SFTPA2, ABCA3), or polymorphisms in MUC5B, causing overexpression of the mucin 5B, or in TOLLIP (an inhibitor of the Toll-like receptors 2 and 4) together to mitochondrial dysfunction are other genetic mechanisms associated with an increased risk of IPF [A growing number of genetic factors predisposing to pulmonary fibrosis have been explored, also thanks to the possibility of conducting genome-wide association studies (GWAS). Particularly, sequence variants in genes for the surfactant proteins causing surfactant dysfunction , which normally modulate and stabilize the alveolar surfactant tension, can induce an increased stress in the endoplasmic reticulum, which finally leads to epithelial-mesenchymal transitions and apoptosis of type 2 alveolar cells.All the reported causative genes for PF show an autosomal dominant pattern of transmission, leading to a 50% chance of transmitting the pathogenetic variant to the offspring. However, the expression of the phenotype is influenced not only by incomplete penetrance, intrafamilial clinical variability and environmental factors but also by the pathomechanism related to the specific gene involved. For example, for genes involved in telomere maintenance, it is reported that the phenomenon of anticipation, is possibly favored by epigenetic mechanisms triggering telomere shortening .MUC5B, a regulatory mucin, are responsible for mucociliary disfunction with impaired clearance and enhanced mucus production, which predisposes to bacterial overgrowth and infections.Moreover, polymorphisms of TERT) and telomerase RNA component (TERC). Other accessory components act to stabilize TERC, such as dyskerin, NHP2, NOP10 and GAR1 [Telomere dysfunction is one of the main drivers of IPF, as many sequence variants in telomere genes have been described in IPF ,37,38,39and GAR1 . The lenand GAR1 ,44.Among the Mendelian telomere disorders, PF is the most common in the adult age, indeed numerous mutations in telomere-related genes have been described in association with IPF ,39,40,41TERT and TERC genes, these mutations can be found also in 2% of sporadic IPF. TERT and TERC mutations are mainly heterozygous (related to an inherited or de novo mutation), thus showing a dominant transmission. It has been hypothesized [PARN or RTEL1, should be considered as risk factors for the development of earlier IPF onset and more rapid progression and thus the risk of death.Whilst 15% of FPF present mutations in thesized ,27 that TERC KO mice), it was hypothesized that adult stem cells of the lung, the alveolar epithelial type 2 cells (AEC type 2), are the most affected by shortening of the telomeres [Since the decreased ability to regenerate damaged or injured lung tissue was experimentally demonstrated in mice models of IPF with TERC mutations , has been described as the strongest risk factor to predispose to IPF both in sporadic and familial cases [MUC5B, which is indeed associated with the failure of the reparative and regenerative mechanisms of the alveoli, mucociliary dysfunction and pollutants retention, which are the basis for the development of honeycombing cysts and fibroproliferative degeneration [dy clear . Particual cases ,54. Thisneration ,56. Exceneration .The frequency of the T allele in the general population and in cohorts of IPF patients has been thoroughly investigated in several studies across the world. A genome-wide association study (GWAS) has found that in the Caucasian population 41.9% of IPF patients and 10.8% of the healthy control group are carriers of the T allele of the rs35705950 . A recenThe Toll-interacting protein TOLLIP acts as an inhibitor of the Toll-like receptors (TLRs) 2 and 4, which are active in the lung. As a consequence, TOLLIP contributes to the suppression of tumor necrosis factor-α (TNF-α) and IL-6 production . SeveralTOLLIP is mainly expressed in the lung by alveolar type II cells, macrophages and basal cells, where it can prevent damage from reactive oxygen species (ROS) induced by mitochondrial damage. Moreover, it can protect bronchial cells and modulate inflammation and autoimmunity via different pathways  ,66.Consistently, IPF outcome might be influenced by SNPs in the TOLLIP gene. Bonella et al. recently found that IPF patients carrying the TOLLIP rs5743890 minor allele had a worse prognosis, with a median reduction in survival of 20 months compared to IPF patients without this mutation . MoreoveAEC type 2 are responsible for the production of the surfactant. Particularly, the surfactant is composed of phospholipids and the following four surfactant proteins: SP-A, SP-B, SP-C and SP-D. Surfactant proteins are synthesized in the endoplasmic reticulum (ER) of AEC type 2, from which they are transported and subsequently stored in the lamellar bodies. Finally, these proteins are secreted in the alveolar space ,69.SFTPA1, SFTPA2, SFTPC and ABCA3—ATP binding cassette subfamily A member 3) are associated with FPF [In the literature, it has been described that several mutations of the genes encoding these proteins  are associated with ER stress and an increased risk of developing lung cancer in smokers [SFTPC gene (the surfactant protein C) lead to a misfolded SP-C, which thus accumulates in the ER, causing ER stress. Particularly, the BRICHOS domain, critical for the SP-C proper folding, is usually the most affected by SFTPC mutations [In detail, variants in the  smokers ; those iutations ,75.SFTPA2 and SFTPC are dominant, ABCA3 mutations are causative of a recessive form of the disease [Finally, rare variants in the gene encoding for the protein ABCA3 have been described as a risk factor for pulmonary fibrosis. ABCA3 is a protein, which in AEC type 2 acts as a transporter protein for lipids through the plasma membranes ,77. When disease .The possible mechanism at the basis of fibrogenesis in patients carrying mutations in the genes encoding for surfactant proteins might rely on the activation of epithelial-to-mesenchymal transition (EMT) induced by ER stress. Indeed, ER stress is able to activate epithelial cell differentiation in mesenchymal cells and AEC type 2 apoptosis. This causes the production and deposition of collagen and the subsequent fibrosis in an alveolar environment, which is poor for functional surfactant proteins ,81,82.Besides genetics and genomics, which help characterize the molecular landscape of IPF and FPF, a major role is also played by epigenetics. Several studies showed indeed that multiple genes are differentially expressed in IPF lung, mainly involved in pathways such as TGF-β signaling, epithelial to mesenchymal transitions, fibroblast proliferation ,84,85. GAll the biological features characterizing PF could be explained by gene expression dysregulation related to epigenetic modifications. Considering the dynamic nature of epigenetic modifications, they represent an attractive druggable target, since epigenetic marks can be reverted by specific treatments, such as histone deacetylases inhibitors (HDACi) .Moreover, distinct episignatures are, indeed, emerging to be disease-specific and the epigenetic profile may be exploited to support the clinical diagnosis. The identification of methylation changes associated with disease development is particularly important for pathologies strongly associated with environmental exposure, as in the case of PF. Epidemiological studies have, indeed, demonstrated the association between exposure to inhaled environmental agents and IPF development, including cigarette smoke, wood dust, metal dust, silica, textile dust and possibly agriculture, farming and livestock ,88. CigaHuman DNA is enriched in CG dinucleotides, especially in the regulatory regions such as gene promoters. These CpG sites can undergo the addition of a methyl group to the cytosine residue. This methylation process is regulated by specific enzymes, essentially DNA methyltransferases (DNMTs), and the presence of methylated CpGs blocks the binding of the RNA polymerase complex to the promoter region and thus silences gene expression. DNA methylation is an epigenetic mark that triggers conformational chromatin changes leading to different expression levels of genes; the general rule is that hypomethylation in gene promoters should result in increased expression of the related genes, while hypermethylation causes a decrease in expression levels. This rule is not always valid if methylation is located in other regulatory genome regions, such as enhancers .MUC5B, PTGER2 (Prostaglandin E receptor 2) and THY1 (Thy-1 antigen).Several genome-wide methylation studies reported multiple differentially methylated regions (DMRs) between IPF lung and healthy controls . The majMUC5B and the rs35705950 risk allele, Helling and colleagues [MUC5B enhancer region encompassing the rs35705950 variant. This enhancer element dynamically binds the transcription factor FOXA2 as well as RNA polymerase II, suggesting its important role in controlling MUC5B expression. Indeed, the authors indicated that increased methylation is associated with increased expression of MUC5B, IPF and the risk allele T at rs35705950.Regarding lleagues  identifi2 (PGE2) pathways are essential to maintain the correct homeostasis of fibroblasts, guaranteeing the appropriate apoptosis. The lungs of IPF patients are substantially resistant to PGE2, which is conditioned by reduced expression of its receptor, E prostanoid 2 (EP2), due to DNA hypermethylation of its promoter, PTGER2 [2 mRNA transcription and thus the PGE2 responsiveness in fibrotic fibroblasts but not in nonfibrotic controls.Prostaglandin E, PTGER2 . The autTHY1 encodes for the thymocyte differentiation antigen 1 (Thy-1), a cell outer membrane glycoprotein also known as CD90. Studies in human and murine lung specimens demonstrated that the absence of Thy-1 promotes myofibroblast differentiation and that this is due to hypermethylation of the THY1 promoter [THY1 seems to be related to hypoxia [Fibroblastic foci typical of IPF are characterized by abnormal myofibroblasts, in which gene expression is completely altered, especially for several “IPF suppressor genes” ,95,96,97promoter ,98. The  hypoxia , and the hypoxia ,101.These studies suggest that alteration of DNA methylation at genomic loci closely related to the pathogenesis of IPF is a crucial factor in the development of IPF and that DNMT-targeted therapies could be a resource for remodeling this process, although further studies on their specificity and adverse effects are needed. Little is known about the role of epigenetic modifications in the development of FPF; nevertheless, environmental exposure can induce disease-specific methylation changes associated with increased risk of disease development, also in familial cases, thus suggesting a role for epigenetic changes, in addition to the genetic predisposition, in FPF .In addition to DNA methylation, remodeling of the chromatin state is also regulated by post-translational modifications of histones that change the conformation of the chromatin complex, leading to different levels of condensation and thus affecting the gene expression of related loci. Histones can be modified through different mechanisms, among which the two most common are methylation and acetylation. Both types of modifications are dynamically regulated by different classes of enzymes responsible for the addition or removal of methyl or acetyl groups from specific histone residues. Histone methylation is controlled by the following two sets of enzymes: histone methyltransferases (HMTs) and histone demethylases (HDMs), while histone acetylation is the product of the dynamic interplay between histone acetyltransferase (HATs) and histone deacetylase (HDAC).Among the enzyme alterations responsible for histone modifications in the pathogenesis of IPF are increased activity and expression of EP300. EP300 encodes for a histone acetyltransferase involved in cell proliferation and differentiation. Rubio and colleagues  demonstrAberrant HDAC activities are also involved in the epigenetic silencing of Thy-1, an already mentioned “fibrotic suppressor surface glycoprotein”. Indeed Thy-1 silencing is regulated not only by promoter hypermethylation but also by histone modifications in lung fibroblasts  and treaThese studies highlight the close interaction between DNA methylation and histone modification and how treatments against the enzymes responsible for regulating these epigenetic mechanisms could be useful in the treatment of IPF.Other emerging pathways involved in the development of the lung, and which seem to be epigenetically influenced in IPF patients are the Hedgehog pathway GLI1 and the WNT pathway of beta-catenin .Genes expression can also be controlled by microRNAs (miRNA), non-coding RNAs composed of 17–25 nucleotides. They interact with the 3′ untranslated region of mRNAs mediating mRNA degradation and gene silencing.Several miRNAs expression profile studies showed that alteration in the expression of specific miRNAs affects fibroproliferation, epithelial-mesenchymal transition and the TGF-β1 signaling pathway ,108,109.Intriguingly, miR-21 plays a key role in IPF. Indeed, miR-21 can stimulate TGF-β thus upregulating the EMT and impairing earlier the forced vital capacity . MoreoveEmerging studies are focusing on the role of long non-coding RNAs (lnc-RNAs) in fibrogenesis, such as an antifibrotic role for FENDRR  and a prAs for methylation changes, studies on ncRNAs have been mainly focused on IPF. However, the role of these RNAs may be played also in FPF, as an additional mechanism influencing the onset and the severity of the condition associated with exposome .Some genes associated with the onset and progression of IPF might support clonal selection and favor cancer transformation.TGF-β1, interleukin-1 receptor alpha (IL1RN), interleukin 8 (IL-8), Toll-like receptor 3 (TLR3), telomerases, tumor protein 53 (TP53), are also associated with cancer. While TP53 can act as an oncogenic driver, the others can sustain neoplastic transformation but cannot induce it. The TP53 gene was found to be significantly mutated in cases of lung cancer associated with IPF. Mutations in the JAK-STAT signaling pathway were also significantly amplified in IPF-associated lung cancer [Interestingly, genes supporting the inflammation and fibrogenesis in IPF, such as g cancer .As already described, mutations in the telomerase genes are one of the main genetic risk factors for pulmonary fibrosis, but the angiogenic and pro-invasive properties they confer could be adopted by yet-transformed malignant cells . MoreoveTTF-1 is mainly expressed in APC type 2, and it regulates the expression of surfactant proteins in the lungs, which are fundamental for the homeostasis of the alveolar milieu [TTF-1 is an oncogene, which might contribute to cell proliferation in cancer and fibrosis since its expression is enhanced in injured lungs [Intriguingly, the thyroid transcription factor-1 (TTF-1), a highly specific biomarker of primary adenocarcinoma of the lung, seems to be implicated also in the pathogenesis of IPF. r milieu . TTF-1 ied lungs .SFTPA1 and SFTPA2, indeed, predispose to IPF through ER stress and consequent alterations in APC type 2, whilst pathogenetic variants of SFTPA2 are responsible for ILD2, an autosomal dominant condition characterized by a strong genetic predisposition to lung cancer. By promoting cell proliferation and fibrogenesis, these mutations can also induce neoplastic transformation [SFTPC [ABCA3, which is well known for its profibrotic action when mutated, is also implicated in the onset and progression of lung cancer and acts as a mediator of chemoresistance in lung neoplasm [A link between IPF and lung cancer secondary to mutations in the genes of the surfactant proteins has begun to be investigated. Polymorphisms of ormation . Similarn [SFTPC . ABCA3, neoplasm .Even if the mechanisms of their role in lung cancer and pulmonary fibrosis are still not well defined, the peroxisome proliferator-activated receptors (PPARs) nuclear receptors seem to play a part, since their deregulation has been described in several inflammatory conditions, such as cancer and atherosclerosis, but also in IPF. PPARs are involved in the regulation of the metabolism of lipids and in cellular proliferation .MMP1), which shows a high rate of genetic mutations in both of these two pathologies. MMP1 is well represented in neoplasms, promoting the spreading of metastases and their invasive potential, and enhancing the EMT in pulmonary fibrosis, angiogenesis and cell migration. Consistently, high levels of MMP1 have been found in the early phases of lung cancer developed in the context of pulmonary fibrosis [Another link between IPF and lung cancer resides in the matrix metalloproteinase 1  and lung cancer, ranging from mutations and polymorphisms of typical genes involved in the fibrogenesis to alterations in oncogenes with a novel potential profibrotic action. Intriguingly, nintedanib, a tyrosine kinase inhibitor currently approved for the treatment of idiopathic pulmonary fibrosis, has been inherited from oncology, underlying again the common background of pulmonary fibrosis and cancer.A recent study based on next-generation sequencing (NGS) and bioinformatics described some genetic and epigenetic pathways that can be influenced by nintedanib, an antifibrotic therapy .Nintedanib is a tyrosine kinase inhibitor, which exerts its antifibrotic effects by targeting and interfering with fibroblast-derived growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR) and potentially inhibiting the transforming growth factor β (TGF-β) signals to downregulating the ECM . The autE2F1, NPTX1, DDX11, PLXNA4 (downregulated) and SLC25A23 (upregulated).Notably, after nintedanib treatment, the authors identified four downregulated and one upregulated genes, which act on the following miRNA-mRNA interactions: E2F1 is a critical transcription factor in the cell cycle and apoptosis, particularly because it is required for the S phase of the cell cycle. By increasing the levels of E2F1, the proliferating and profibrotic effects of VEGF, epidermal growth factor (EGF) and keratinocyte growth factor (KGF) can be exerted. Nintedanib manages to reduce the levels of E2F1 in the treated fibroblasts, and this might lead to slow fibrogenesis in IPF.NPTX1 belongs to the family of neuronal pentraxin , thus itDDX11 promotes cell proliferation and metastasis in tumoral cells, whilst it might induce the proliferation of fibroblasts in IPF. Nintedanib manages to suppress the DDX11 signaling, thus inhibiting fibroblast’s proliferation.PLXNA4 is also downregulated by nintedanib treatment. Since its action is to promote the vascularization of the tumors, induced by VEGF, its downregulation can decrease the angiogenesis in IPF.Finally, SLC25A23, which, in contrast, is upregulated by nintedanib, induces cell death through oxidative stress. It has been hypothesized that upregulating SLC25A23, nintedanib can reduce fibroblast proliferation, induce their apoptosis and decrease angiogenesis in IPF.Recently, another interesting study focused on the efficacy and safety of nintedanib and pirfenidone in a group of patients with pulmonary fibrosis carrying mutations in telomerases genes. In this work, authors found that both antifibrotic treatments were associated with a reduced decline of FVC, without observing unexpected adverse events .Moreover, another study demonstrated that also pirfenidone can slow the rate of progression of EMT modulating several gene-induced pro-fibrotic pathways . PirfeniSince available drugs are not able to cure IPF, several studies have addressed the use of gene therapies as potential approaches to attenuate a wide range of processes involved in fibrosis. To date, despite the potential benefits of gene therapy, no clinical trials for treating IPF have not been launched. Developing novel drugs to treat IPF is, indeed, challenging due to the complex pathogenesis of the disease and the difficulty of modeling the disease in animals. Currently, available animal models are not specific for IPF but only recapitulate some aspects of pulmonary fibrosis artificially induced by different chemicals . Initial studies exploring the potential application of gene therapies to IPF focused on inducing targeted gene overexpression using both nanoparticles and viral vectors ,130. ThiMore recently, the use of gene silencing by siRNA  for treating PF was investigated in several studies that described the efficacy of multiple siRNAs combined with antifibrotic compounds in treating several aspects of PF . Very feAltogether, these studies support the applicability of gene therapy to suppress the progression of fibrosis. However, no gene therapy approach has demonstrated the capability to reverse established fibrosis.Nowadays, the possibility of exploring the genetic and epigenetic basis of pulmonary fibrosis more in depth represents a clinical and scientific challenge that could, in the near future, help in both the diagnosis and the development of targeted therapy for this devastating disease.Hopefully, genetics might soon support the diagnostic algorithm of IPF, integrating data from radiology and pathology at the molecular level. To this end, it is essential to underline the role the genetic counseling in referring to genetic analysis of the population at risk of familial forms , and in the correct interpretation of the considerable amount of data that can be made available by genome-wide array genetic analysis.Reversing the epigenetic changes capable of influencing the genesis and progression of pulmonary fibrosis might be an interesting research perspective, as well as designing trials for targeted therapy at the genetic level.Since IPF and PFF are rare diseases, it is essential that knowledge of the genetic basis of pulmonary fibrosis should be shared with all other healthcare personnel involved in the management of ILD.An increasing role of genetics and epigenetics in the pathogenesis and prognosis of IPF and PFF is emerging. As described above, specific Mendelian mutations in telomere genes are able to determine the development of familial forms of pulmonary fibrosis, with an earlier onset and often a more severe prognosis. Likewise, gene variations capable of altering surfactant proteins are known to be responsible for the fibrosing disease, some of which affect children. Finally, polymorphisms of mucins, i.e., MUC5B or Toll-like receptor inhibitors (TOLLIP), have been associated with a greater risk of developing pulmonary fibrosis.Many of the genes and pathways involved in pulmonary fibrosis development are today known because of their involvement in the Mendelian form and GWAS studies. Beyond the Mendelian forms, many of the same loci and pathways may be affected by variants or epigenetic modifications that can modify the risk of diseases in the presence of environmental triggers.Although the genetic predisposition to pulmonary fibrosis is known, the molecular diagnosis of familial cases is probably still underestimated, and this could be related to the incomplete penetrance of the disease or the lack of information from the patient’s pedigree. In order to recognize the familial cases, it is important to identify the risk in family members not only for pulmonary fibrosis but also for possible related conditions, such as lung cancer and bone marrow failures. In addition, it is emerging that epigenetic mechanisms can affect the development and prognosis of pulmonary fibrosis. DNA methylation of CpG sites, histone post-translational modifications and non-coding RNA gene silencing are mechanisms that should also be explored in fibrogenesis.Interestingly, epigenetic signatures of disease can have a clinical utility as biomarkers or druggable targets since epigenetic marks can be reverted.Of interest, genes supporting the inflammation and fibrogenesis in IPF, such as TGF-β1, interleukin-1 receptor alpha (IL1RN), interleukin 8 (IL-8), Toll-like receptor 3 (TLR3), telomerases, tumor protein 53 (TP53), are also associated with cancer and genome-wide methylation studies, as well as gene expression studies, showed several parallelisms between the pathogenetic mechanisms that drive IPF and lung cancers. Further studies are needed to better elucidate the molecular mechanisms of the relationship between pulmonary fibrosis and lung cancer.Finally, data are emerging on the molecular pathways, at both the genetic and epigenetic levels, which form the basis of the efficacy of the antifibrotic therapies.


Adhesion molecules regulate cell proliferation, migration, survival, neuritogenesis, synapse formation and synaptic plasticity during the nervous system’s development and in the adult. Among such molecules, the neural cell adhesion molecule L1 contributes to these functions during development, and in synapse formation, synaptic plasticity and regeneration after trauma. Proteolytic cleavage of L1 by different proteases is essential for these functions. A proteolytic fragment of 70 kDa (abbreviated L1-70) comprising part of the extracellular domain and the transmembrane and intracellular domains was shown to interact with mitochondrial proteins and is suggested to be involved in mitochondrial functions. To further determine the role of L1-70 in mitochondria, we generated two lines of gene-edited mice expressing full-length L1, but no or only low levels of L1-70. We showed that in the absence of L1-70, mitochondria in cultured cerebellar neurons move more retrogradely and exhibit reduced mitochondrial membrane potential, impaired Complex I activity and lower ATP levels compared to wild-type littermates. Neither neuronal migration, neuronal survival nor neuritogenesis in these mutants were stimulated with a function-triggering L1 antibody or with small agonistic L1 mimetics. These results suggest that L1-70 is important for mitochondrial homeostasis and that its absence contributes to the L1 syndrome phenotypes. Complex neural functions are achieved by the structural and functional interactions of neural activities, which strongly depend on the functional integrity of the mitochondria ,2,3,4. MMitochondria are not only important for the postmitotic and differentiated neurons, but also for neural progenitor cells during neurogenesis . Thus, dL1 in mice), inhibition of the mitochondrial import of L1-70 or prevention of myelin basic protein-mediated proteolytic generation of L1-70 in cell cultures all lead to reduced mitochondrial Complex I activity, impaired mitochondrial membrane potential, fusion, fission and motility, as well as increased retrograde mitochondrial transport [Because of the need to maintain and even improve mitochondrial function, investigations into mitochondrial heath are essential. A molecule that was recently shown to improve mitochondrial function is the cell adhesion molecule L1, a member of the immunoglobulin superfamily ,23. L1 cransport . Furtherransport . Howeverransport ) and genransport ) showingransport  . On this substrate, the neurite outgrowth and survival of neurons from mutant mice were comparable with those from wild-type neurons A,B. NextWe next determined the consequences of the absence of L1-70 for Schwann cell function, since Schwann cells also express L1, and L1 was shown to be involved in Schwann cell axon interactions ,35. The These results distinguish the neurons and Schwann cells from the L1-70-lacking mice from the cells of the L1-201 mutant, which could be stimulated by function-triggering L1 antibody 557 and L1 mimetics, but were impaired under basal conditions .We next analyzed mitochondrial activity and transport in neurons from L1/858-863, L1/687 and L1-201 mutant mice. In L1-70-lacking L1/858-863 and L1/687 neurons, the velocity and mobility of the mitochondria was normal, but the mitochondria moved more retrogradely than the mitochondria from wild-type neurons A–C. The Mitochondrial functions of L1-201 mutant mice—in which the L1-70 fragment is generated—showed impaired neuronal migration, enhanced cell death and a reduced process length of Schwann cells on the PLL substrate but enhanced process length, and enhanced migration and survival after L1 agonist treatment . InteresComplex I activity and ATP levels were normal in L1-201 mitochondria, whereas the membrane potential was higher in L1-201 mitochondria compared with that of wild-type neurons A–C. FurtOur results show that L1/687 and L1/858-863 mice exhibit lower Complex I activity, reduced mitochondrial membrane potential and reduced ATP levels, whereas their mitochondria move more retrogradely and their velocity and mobility are normal. This indicates that the generation of the L1-70 fragment is important for mitochondrial Complex I activity, production of ATP and generation of normal mitochondrial membrane potential, but not for mitochondrial velocity or mobility. A comparison with mitochondria from L1-201 mice showed that these mitochondria also move more retrogradely, suggesting that the absence of L1-70 is not responsible for the retrograde movement of mitochondria from L1/687 and L1/858-863 mutant neurons, but is indicative of stressed or unhealthy mitochondria in these mutants.Fragments of L1 were previously shown to be imported into the cytosol and from there into intracellular organelles such as the mitochondria and the nucleus ,36,37. IThe mitochondria of neurons in which L1-70 is absent and the mitochondria of neurons with the D201N mutation moved more retrogradely than anterogradely, which indicates that the absence of L1-70 is not responsible for the enhanced retrograde transport but other functions of L1 are responsible, such as L1 signal transduction or the interaction of full-length L1 with its binding partners.Previous studies showed that treatment of wild-type cerebellar neurons with the function-triggering antibody 557 and the L1 mimetics duloxetine, piceid, tacrine, ethinyl estradiol, crotamiton and honokiol enhanced the expression of L1, stimulated the generation of L1-70 and enhanced neuritogenesis as well as neuronal migration and survival ,33. SchwNeurons from mice without L1-70 exhibited reduced neurite outgrowth and neuronal survival and migration when the cells were stimulated with antibody 557 or L1 agonists, but were not affected without stimulation. This feature also distinguishes L1-70-deficient neurons from L1-201 neurons with impaired basal neuronal functions but susceptibility to stimulation by antibody 557 or L1 agonists . These r2+. When mitochondria are aged or damaged, they are retrogradely transported back to the cell soma to be degraded [After showing that L1 plays important roles in the functions of mitochondria , we invedegraded . Throughdegraded . Neuronsdegraded . DeficieWhen their function is impaired, the mitochondria contribute to severe pathologies of the nervous system, not only due to metabolic insufficiency but also to the production of ROS and activation of caspases ,11,39, wGene-edited mice expressing L1 with an arginine-to-alanine exchange at Position 867 in the first FNIII domain (L1/687 mutant mice), with a mutation of the dibasic sequence RKHSKR to SKHSSS at Positions 858–863 in the third FNIII domain (L1/858-863 mutant mice)  and with4 cells/well in 0.01% poly-L-lysine -coated 48-well tissue culture plates  in a defined serum-free medium  supplemented with 2 mM L-glutamine, 4 nM L-thyroxine, 1 mg/mL BSA, 12.5 μg/mL insulin, 30 nM sodium selenite, 100 μg/mL transferrin, 0.1 mg/mL streptomycin and 10 U/mL penicillin ) and allowed to settle for 30 min. They were then treated with 50 µg/mL of L1 function-triggering antibody 557 directed against amino acids 817–835 at the transition between the second and third FNIII-like domains ([6 cells/mL in PLL-coated 48-well tissue culture plates (ThermoFisher Scientific) and maintained overnight in a defined serum-free medium as indicated above [2O2 for 24 h. Live and dead cells were then stained with calcein-AM (ThermoFisher Scientific) and propidium iodide (Sigma-Aldrich) and imaged with a Zeiss AxioObserver.A1 microscope (Carl Zeiss) with a 20× objective (aperture 0.4) and AxioVision 4.6 software (Carl Zeiss) [https://imagej.nih.gov/ij/index.html; RRID:SCR_003070, 8 March 2022). For determining cell migration, cerebellar explants were prepared from two to three 6- to 7-day-old male mice per genotype and experiment as described, and the migration of neurons was determined from 12–15 explants per condition and experiment [Cultures of dissociated cerebellar granule neurons were prepared from 6- to 7-day-old male mice as described . In eachdomains  . Live anperiment . Brieflyperiment . Experim4 cells/well into PLL-coated 48-well tissue culture plates (ThermoFisher Scientific) and allowed to settle for 30 min. Cells were then treated with 50 µg/mL of antibody 557 or 100 nM of duloxetine for 24 h. After fixing and staining with 1% toluidine blue and 1% methylene blue in 1% sodium tetraborate, images of the process were taken, and the lengths of the process from at least 100 cells per condition and experiment were quantified using an AxioObserver.A1 microscope with a 20× objective (aperture 0.4) and AxioVision 4.6 software (Carl Zeiss) [Schwann cells were isolated from male 6- to 7-day-old mice as described . In eachl Zeiss) . Experim® Red CMXRos . A MitoTracker stock solution (1 mM) was diluted to a final concentration of 50 nM in the pre-warmed cerebellar neuron culture medium. Cerebellar granule neurons (density: 1−2 × 106 cells/well of a 6-well plate containing a 20 mm glass coverslip) were prepared as stated above and cultured for two to three days in a medium as indicated above containing 5% horse serum. The medium was then replaced with a serum-free medium, and the cells were incubated with 50 nM of MitoTracker for 30 min at 37 °C. This solution was then replaced with fresh serum-free medium, and the cells were analyzed at 37 °C under 5% CO2 by time-lapse imaging using an upright Nikon Eclipse Ti microscope  combined with spinning disk  live-cell confocal technology (Visitron Systems) and a 100× objective (aperture 1.45). For live cell imaging, a 561 nm argon laser was used at 10% intensity, and images were taken at intervals of 2 s for a duration of 5 min. Videos were acquired using the VisiView 5.0 software (Visitron Systems). To determine mitochondrial velocity, mobility and the direction of mitochondrial transport (anterograde or retrograde), we used the kymograph (time space plot) plugin and the velocity tool from ImageJ . The kymograph represents a time and space plot: the x-axis indicates the distance, and the y-axis shows the time. Vertical lines represent no movement, while diagonal lines show mobile mitochondria. With respect to the position of the cell soma, the direction (right or left) of the diagonal lines indicates retrograde or anterograde transport, respectively [Mitochondria were labeled with MitoTrackerectively . Mitochoectively ,47. For The dual-emission potential-sensitive probe JC-1 iodide  was used to measure the membrane potential of the mitochondria . JC-1 en6 cells/mL onto 22 µm glass coverslips coated with PLL and cultured in a serum-free medium for two days. Afterwards, cells were stained with 3 µM of JC-1 in Hank´s balanced salt solution  for 30 min, incubated with HBSS alone for 15 min and then observed under a spinning disk microscope with a 60× objective (aperture 1.4). For detecting mitochondria with high mitochondrial membrane potential, a rhodamine filter set was used together with the fluorescein filter for detecting depolarized mitochondria with low mitochondrial membrane potential. Experiments were carried out in duplicate and performed independently three times using one mouse per genotype and experiment. The total cell fluorescence intensity was calculated for the green and red channels separately, and the red to green fluorescence intensity ratio was determined from 10 neurons per image and 10 images per group and experiment.To determine the mitochondrial membrane potential, cerebellar granule cells were prepared as stated above and plated at a density of 1−2 × 10® Mitochondrial Complex I Activity Assay Kit . Experiments were carried out in duplicate and performed independently three times using four (L1/858-863), six (L1/687) or nine (L1-201) mice in total per genotype. Only Complex I activity was determined in the present study, since we had found that other complexes’ activities were not altered by the L1-70 fragment [Whole brains were isolated from 6- to 8-day-old male mice, frozen in liquid nitrogen and stored at −80 °C until use. For isolation of the mitochondria, the Mitochondria Isolation Kit for Tissue from ThermoFisher Scientific  was used. For determining Complex I activity, mitochondria were applied to the MitoCheckfragment .® 2.0 Cell Viability Assay  according to the manufacturer´s protocol. In brief, cerebellar granule cells were cultured in a serum-free medium as indicated above at a density of 2.5 × 105 cells/well in 48-well plates for 2 days. Afterwards, cells were scraped off into 200 µL of serum-free medium, 100 µL of the supernatant was transferred into white 96-well plates and 100 µL of BacTiter-Glo was added to the wells. Plates were incubated for 5 min at room temperature with gentle shaking and then the luminescence was measured using a luminometer . ATP concentrations were determined using an ATP standard curve. Experiments were carried out three times independently in triplicate using three (L1/687), five (L1-201) and six (L1/858-863) mice in total per genotype.ATP levels were determined using the BacTiter-Glo2. The medium was then replaced by HBSS without phenol red, and cells were imaged under a spinning disk microscope with a 40× objective (aperture 1.2) and with an excitation wavelength of 488 nm. Experiments were carried out in duplicate and performed independently three times; for each condition and experiment, 10 images were taken for analysis.Intracellular ROS were monitored using the ROS-sensitive fluorescent probe 2′,7′-dichlorofluorescin diacetate , which penetrates into cells rapidly and is hydrolyzed by ROS into a fluorescent green dye. Cerebellar granule cells from 6- to 7-day-old mice (one mouse per genotype and experiment) were prepared as stated above and seeded onto glass coverslips as mentioned above, maintained in the culture for 3 days in a serum-free medium and stained with 10 µM of DCFH-DA for 30 min at 37 °C and 5% COt-test was used to compare two groups, whereas for comparisons of more than two groups, we performed ANOVA followed by Tukey’s post-hoc test for multiple comparisons. Groups containing small sample numbers or data that were not normally distributed were analyzed using the Mann–Whitney U-test for comparing two groups or the Kruskal–Wallis test by ranks followed by Dunn’s multiple comparison test when there were more than two groups. The statistical tests used for comparisons are indicated in the figure legends. Analyses were performed using SPSS , SigmaPlot  or GraphPad  software.All numerical data are presented as group mean values with the standard error of the mean (SEM) or standard deviation (SD); for small sample numbers, individual data are additionally indicated. The normal distribution of the data was determined using the Shapiro–Wilk test or the D’Agostino–Pearson test. For data with a normal distribution, Student’s


IV and non-linearity of FN curves at room-temperature can be interpreted by the adsorption effects. Water is speculated as the most responsible gas specie. We have calculated the work function of graphene by VASP. The results show that water adsorption will lower the work function of the graphene edge, while increasing the work function of the graphene surface.Water adsorption on graphene edges was studied by field emission (FE) experiments and first principles simulation. By analyzing the FE current change with temperature, it was concluded that the intrinsic FE of a graphene edge is consistent with Fowler–Nordheim (FN) theory. The noise of  Water adsorption on graphene edges was studied by field emission (FE) experiments and first principles simulation. Small gas molecules such as H2O, H2, O2, CO, NO2, and NO, will influence the electronic structure and other properties of graphene,16–26 the adsorption of some metal atoms such as lithium27 potassium28 have been calculated. However, there is no convenient and efficient experimental method to study the adsorption on graphene edge. Graphene edge show significant field emission (FE) ability,29–32 which can be a very suitable and simple method to study the adsorption on nanomaterial. We have studied the water adsorption on multiwalled carbon nanotube by analyzing the FE behavior at different temperature.33 In this paper, we have studied water adsorption on graphene edge by FE method. It has been found that the water adsorption will lower the work function of graphene edge. The first principle calculation based on VASP further verified the experimental results.Graphene, a two-dimensional (2D) single layer of carbon atoms bonded in a hexagonal lattice,2.34 Scanning electron microscopy (SEM) and Raman spectroscopy indicate that the sample is few-layer graphene. 35 The graphene field emitter is fabricated by sticking them on a molybdenum wire of 0.1 mm diameter with organic binder, which can be thoroughly evaporated after being heated at 350 °C in air a few minutes. The FE experiment was conducted in a high-vacuum chamber with a base pressure of 10−5 Pa. Graphene were prepared by the chemical method.IV curve of the graphene at room temperature (RT). Here a DC voltage sweeping from 300 V to 1100 V was applied to the sample. It can be seen that the curves show obvious noise. The emission current is 0.2 μA at 3.75 V μm−1 and 4 μA at 5.5 V μm−1. IV curve of the graphene at 1198 K. It can be seen that the IV curve is very smooth. 36 heating can be used as a useful method to remove adsorbents. The dwelling time of the adsorbents will be shortened at high temperature. Therefore, the FE at 1198 K in this experiment is determined as the intrinsic FE of graphene after the removal of adsorbents .37J is the current density, λM a macroscopic pre-exponential correction factor, a and b are constants , ϕ is the work function of the emitter (4.74 eV for graphene33), E is the applied electric field38 . β is the local electrical field enhancement factor, vF (correction factor) is a value of the Schottky–Nordheim barrier function v. The field enhancement factor β can be calculated from the slope ‘m’ of the FN curves (the curves of ln(1/V2) versus 1/V), using the following equation.According to the FN equation,β) of graphene was calculated and listed in β of graphene was 13 063.81424, 11 725.88950, 10 676.06139 at 830V–947 V, 948–973 V, 994–1052 V. There is no big difference for the β of three segments, which is also close to the aspect ratio estimation based on the SEM image shown in β verified that the FE comes from graphene edge. Because adsorption can not change geometric structure of graphene, the β at RT can be viewed as almost same as that at high temperature. The work function at RT calculated was 3.29 through solving β and the slope of FN plot at RT. The substituted β was the average value of three segments at high temperature. The work function at RT was small than this calculated by the Zhu F.33 This implies that adsorption can lower the work function of graphene edge.The field-enhancement factor 40 formalism of DFT, as implemented in the VASP.41 The adopted exchange–correlation functional is the generalized gradient approximation with the Perdew–Burke–Ernzerhof (PBE).42 The cutoff energy for the plane wave basis set was taken as 400 eV. The geometry optimization of each isomer was carried out till the energy was converged to an accuracy of 10−4 eV. Brillouin zone integration is performed using Monkhorst–Pack grids43 for all calculations. We build three kinds of models as shown in 3 in K-point sampling is chosen as 5 × 5 × 1 and 1 × 1 × 1 for the slab and the cubic, respectively.Work function is the most direct parameter which can reflect the influence of the adsorption. We have calculated the work function of H2O in three kinds of models as shown in 2O and the graphene as shown in 2O and the graphene surface up to 3.70 Å after relaxation. The interaction between them is only about 0.18 eV. In order to affirm our results, we simulate the graphite surface with five-layer graphene as shown in 2O and the surface of graphite is up to 3.81 Å after relaxation. The interaction between them is 0.23 eV. Since the FE and adsorption/desorption happened on graphene edge in our experiment, we simulate the adsorption of H2O on the edge of graphene as shown in 2O and adsorb at two zig–zag carbon atoms after relaxation. The adsorption energy of H and hydrogen bond is up to 5.93 eV, which is a strong interaction. Obviously, it is physical adsorptions for H2O on the surface of graphene and graphite, and it is chemical adsorption for H2O dissociation on the edge of graphene.We calculated the adsorption of H2O are very close to the calculated work function using the average electrostatic potential of 7 × 7 pure grapheme44 and the experimentally measured work function 4.45–4.74 eV.33,45–47 It can be found that work function for graphene slabe surface increase from 4.24 eV to 5.15 eV due to H2O adsorption, work function for 5-layer graphene increase from 5.00 eV to 5.09 eV due to H2O adsorption, while work function for graphene edge decrease from 5.73 eV to 5.63 eV due to H2O adsorption. This is in good accordance with our experimental results that the FE comes from graphene edge and the FE current change with the adsorption/desorption.The work functions results are tabulated in 4.2O has calculated by VASP. The calculated results show that the water adsorption will lower the work function of graphene edge, while increase the work function of graphene surface. This is in good accordance with the experimental results.In summary, the water adsorption on graphene edge has been studied. It was found that the adsorption induced the deviation from the FN model at RT. After removing the adsorbates by heating, the intrinsic FE of graphene edge follows the FN model very well. Water is speculated as the most responsible gas specie. The work function of graphene with HThere are no conflicts to declare.


Metamaterial absorbers (MMAs) that absorb electromagnetic waves among an ultra-broad frequency band have attracted great attention in military and civilian applications. In this paper, an ultra-broadband and highly-efficient MMA is presented. The unit cell of the proposed MMA was constructed with two cross-placed stand-up gradient impedance graphene films, which play a key role in improving impedance matching. Considering the trade-off between absorbing performance and processing complexity, in our design, we adopted the stand-up graphene films that have a gradient with three orders of magnitude in total. The simulated results of the proposed absorber show an ultra-broadband absorption (absorptivity > 90%) from 1.8 GHz to 66.7 GHz and a highly-efficient absorption (absorptivity > 97%) in the range of 2–21.7 GHz and 39.6–57 GHz. The field analysis was adopted to explain the mechanism of the proposed absorber. To validate this design, a prototype of 20 × 20 units was processed and assembled. The graphene films were processed with graphene conductive ink using screen print technology. The measured results are in good agreement with the simulated ones. The proposed absorber may find potential applications in the field of stealth technologies and electromagnetic interference. Metamaterials are arrays of the periodic arrangement of subwavelength artificial units, with the electromagnetic properties undiscovered in natural mediums. It has attracted more and more attention because of its ability to control electromagnetic energy arbitrarily, and a large number of radio frequency devices based on metamaterials have emerged. By designing the structure of unit cells, the electric or magnetic resonance will occur in the metamaterials at the desired frequency band. The incident electromagnetic wave will enter the metamaterials without reflections and be stored in it. Since all parts of the structure are lossy, such as metal, substrate, and lumped elements, the incident energy will be absorbed and lost by absorbers. MMAs are widely used in the field of stealth technologies and electromagnetic interference/compatibility for their flexible design. Compared with traditional absorbing materials, the reported MMAs usually have a broader operating band and a lighter weight. Moreover, the center frequency could also be designed to the desired one easily. However, the absorptivity of traditional absorbing materials is higher than that of MMAs. So, it is important for MMA to achieve an ultra-broadband and highly-efficient absorption, which is an essential indicator of absorbers for practical applications.One of the most classic microwave absorbers, the Salisbury absorption screen , is compGraphene, as one of the most promising materials in the design of MMAs, has attracted wide attention in recent years ,6. SinceIn this paper, an ultra-broadband and highly-efficient metamaterial absorber with stand-up gradient impedance graphene films is proposed. This paper is arranged as follows. In In this part, we will present the proposed design and its performance in detail. We will indicate how this idea emerges as well. Firstly, the structures of the proposed MMA are presented in t as support. The p and g, respectively. The view in The unit cell, as shown in In the case of an extreme broadband frequency response, the results calculated by the Time Domain Solver are more accurate. So, the full-wave simulation was performed on CST Studio Suite 2021 with the Time Domain Solver in this paper. The simulation results under the TE and TM polarized incident wave are shown in As shown in To demonstrate the superiority of the proposed MMA over the reported 3D absorbers with stand-up uniform resistive films , we haveThe theory of small reflections  proves tN). If we increase N, the step changes in the characteristic impedance between the sections would become smaller, and the transformer geometry approaches a continuously tapered line. Please note that, since the electrical length . So, we can change the sheet resistances of graphene films by adjusting the film thickness.To verify the proposed absorber with gradient impedance graphene films, a prototype constructed with 20 × 20 units was fabricated and measured. In this paper, the graphene films were processed with graphene ink using screen-printing technology. The preparation and characterizations of graphene conductive ink have been reported in our previous works ,17,18. TIn terms of screen-printing technology, the thickness of printed film is affected by the mesh density of the screen, the printing force/angle, and the viscosity of ink. However, it was difficult for us to control these parameters precisely since we printed films manually with a manual screen printer. Finally, to facilitate processing and increase precision, we controlled the sheet resistances of graphene films by the number of print passes, because increasing the times of printing results in an increase in thickness. For example, in this paper, the graphene films with sheet resistances of 400, 200, and 100 correspond to 1, 2, and 4 print passes, respectively. That is why we keep the sheet resistances of graphene as a multiplicative relationship in simulations.The grooves on PMMA were reserved for assembly as in the schematic in The reflection coefficient was measured using the free space method. The measurement set-up is shown in The comparison of measurement and simulation results is shown in The performance comparison between the proposed MMA and other reported ultra-broadband absorbers is shown in It is well known that a 3D absorber can easily realize ultra-broadband absorption. However, in terms of the highly-efficient absorption with an absorptivity larger than 97%, it is also difficult for 3D absorbers to realize during a broad band. For example, the highly-efficient absorption bands in ,4,19 areCompared with those works, the proposed absorber exhibits an ultra-broadband and highly-efficient absorption at the same time due to the stand-up gradient impedance graphene films. The adopted gradient impedance structure maintains the performance at a low frequency efficiently. The stand-up resistive films structure creates the ultra-broad operating band.In this paper, we presented an ultra-broadband and highly-efficient metamaterial absorber with stand-up gradient impedance graphene films. The proposed absorber shows the ability of ultra-broadband and highly-efficient absorption. The theory of small reflections was used to help with understanding the better matching brought by gradient impedance. A field analysis was performed to illustrate the mechanism of ultra-broadband absorption. To verify our design, we fabricated a prototype with 20 × 20 units. In fabrication, conductive graphene ink and screen printing technology were adopted. To save processing cost and time, the sheet resistance of graphene in the gradient impedance structure was set as a multiplicative relationship. Then, we could print films with different sheet resistances by changing the print times. The measured results are in good agreement with simulated ones, which indicates that the design method of gradient impedance is effective. The proposed absorber realizes a highly-efficient absorption with an absorptivity larger than 97% during the most commonly used radar band (2–22 GHz), which makes it of great practical value and has application prospects in the field of stealth technologies.


The optical forces on the nanoparticles can be controlled by modulating the position of LSPR excitation. Controlling the position of LSPR excitation by bias voltage gates to configure the Fermi energy of graphene disks, the nanoparticles can be dynamically transported to arbitrary positions in the 2D plane. Our work is integrated and has multiple functions, which can be applied to trap, transport, sort, and fuse nanoparticles independently. It has potential applications in many fields, such as lab-on-a-chip, nano assembly, enhanced Raman sensing, etc.Optical tweezers are key tools to trap and manipulate nanoparticles in a non-invasive way, and have been widely used in the biological and medical fields. We present an integrated multifunctional 2D plasmonic optical tweezer consisting of an array of graphene discs and the substrate circuit. The substrate circuit allows us to apply a bias voltage to configure the Fermi energy of graphene discs independently. Our work is based on numerical simulation of the finite element method. Numerical results show that the optical force is generated due to the localized surface plasmonic resonance (LSPR) mode of the graphene discs with Fermi Energy E Since Ashkin first introduced the concept of optical tweezers through experiments and theoretical works in the 1970s , this teGraphene is a new two-dimensional material with a single-layer carbon atom structure. Due to its zero bandgaps and unique photoelectric properties, graphene has gained much attention in recent years due to its unique optical properties ,34,35,36Here we theoretically propose integrated multifunctional graphene discs 2D plasmonic optical tweezers for manipulating nanoparticles, which can trap and transport nanoparticles anywhere in the 2D plane by applying bias voltage without a preset path. Our work is based on numerical simulation of the finite element method. The distribution of optical forces on the nanoparticles and the trapping potential are simulated theoretically using the finite element method. Further, we perform simulations of the photothermal fluid and estimate the magnitude of other major forces on the nanoparticle, including the Brownian motion force, the Stokes’s drag force, and thermophoretic force. We numerically demonstrate the ability of this system to trap, transport, and fuse nanoparticles through the Langevin equation, and plot the motion trajectory of the nanoparticles. This work can be applied to trapping, transporting, sorting, and fusion of nanoparticles flexibly and has potential applications in many fields, such as optical sensing, enhanced Raman sensing, biophysics, Opto-mechanic, etc.n = 1.33) under a normal incident plane wave with an intensity of 1 mW/µm2. The material of the insulator substrate layer is designated as BaF2 (n = 1.45), which has high transmittance in the mid-IR and has been proven to be applicable in graphene optical tweezer systems [ systems . We choo systems . When th systems . Monolay systems . The chaWe perform a full 3D simulation using a finite element method (COMSOL Multiphysics). In our numerical study, Graphene is modeled as a two-dimensional transaction boundary condition with a thickness of 0.34 nm . The KubHere lated by :(2)Vg=td0 and εd are the dielectric constant and the thickness of the gate oxide. 6 m/s is Fermi velocity. dt is the distance from the graphene disc to the bias voltage gate. We use the Maxwell stress tensor to calculate the time-averaged optical force on the nanoparticle [Here εparticle ,55.(3)〈S is the outer surface of the nanoparticle and n is its discrete normal vector, T〉 is the Maxwell stress tensor which can be governed as:Here E and H are the intensity vectors of the electric and magnetic fields on the surface of the particle, respectively. Through Helmholtz Hodge decomposition, the optical force can be decomposed into conservative force and non-conservative force. We only take the conservative force into consideration [Here deration ,57. The deration :(5)Ur=−∫It is well known that plasmonic systems with different structures have specific resonance wavelengths. To better understand the resonance distribution of a graphene disc under incident light, We set up a probe at 50 nm above the center of the graphene disc (the center of the nanoparticle) to determine the efficiency of near-field enhancement. A normalized intensity map is represented in 0 = 1 mW/µm2, which has much lower than other plasmonic optical tweezer systems [x-axis, with y-center = 0 and z-center = 50 nm. When x-center = −160 nm~160 nm, Fz is always negative (Fz < 0 pN), which proves that the nanoparticle will be pulled to the interface between the dielectric material and the trapping environment. When x-center > 0, Fx is a positive force (Fx > 0 pN), x-center < 0, Fx is a negative force (Fx < 0 pN), x-center = 0, Fx = 0 pN. This means that the nanoparticle will be trapped by the optical force in the center of the graphene disk along the x-axis. As the result shown in x-axis, we calculate the trapping potential of the nanoparticle along the x-axis, which is greater than 10 KBT to ensure stable trapping. Corresponding to the graphene disks diagram at the top of the figure, the trapping region in the x-axis direction contains the entire area of the adjacent graphene discs. This demonstrates that, by dynamically configuring the Fermi level of graphene, the motion of nanoparticles can be controlled along the x-axis. y-axis, with x-center = 0 nm and z-center = 50 nm. Fy is a positive force (Fy > 0 pN), y-center < 0, Fy is a negative force (Fy < 0 pN), y-center = 0, Fy = 0 pN. This means that the nanoparticle will be trapped by the optical force in the center of the graphene disk along the y-axis. As the result shown in y-axis, we calculate the trapping potential of the particle along the y-axis, which is greater than 10 KBT to ensure stable trapping. Corresponding to the graphene disks diagram at the top of the figure, the trapping region in the y-axis direction contains the entire area of the adjacent graphene discs. This demonstrates that, by dynamically configuring the Fermi level of graphene, the motion of nanoparticles can be controlled along the y-axis. z-axis, with x-center = 0 nm and y-center = 0 nm. d is the distance from the bottom of the nanoparticle to the graphene disc. It can be found that the larger the radius of the nanoparticle the greater the optical force on it. By the line integral of the force along the z-axis, we calculate the trapping potential of the nanoparticle on the x-axis. The result is shown In BT. This can be improved by appropriately increasing the incident light intensity.We continue to investigate the optical forces on the nanoparticle  at different locations, Fermi energy of the graphene disc is configured as 0.6 eV. We assume that the intensity of the incident light is I systems ,43. The f = 0.6 eV) under an incident light intensity I0 = 1 mW/µm2. s − Te. Ts is the temperature at each point when the simulation reaches a steady state. Te is the operating room temperature. ΔT increases only 2 °C compared to room temperature. To estimate the thermal behavior in the proposed system, The thermally induced convective distribution is represented in We next numerically investigate the temperature distribution and convection field near the graphene disc r(t)=c dipole ,63.z-axis for the calculation of the force of the optical gradient. We propose here a 3 × 3 array of graphene discs. As mentioned before, the optical forces on the nanoparticles can be switched quickly by controlling the switching states of the adjacent trapping positions. 5 times. The nanoparticles are released at moment 0, and the initial positions are set at ,  in the x-y plane (z = 50 nm plane), respectively. As is shown in The optical force on the z-axis will make the nanoparticles cling to the partition interface of water and insulator and move in the x-y plane. So we only consider the motion of the nanoparticle in the x-y plane. We choose the electric field intensity at 50 nm above the 0 = 1 mW/µm2. Finally, we demonstrate its ability to trap, transport, and fuse nanoparticles with a 3 × 3 array of graphene discs by means of the Langevin equation. We anticipate that it will become a new tool for nanoparticle manipulation and open new directions for its wide range of potential applications in lab-on-chip, nano-assemble, enhanced Raman sensing, etc.In summary, integrated multifunctional graphene discs 2D plasmonic optical tweezers for manipulating nanoparticles is shown to be achievable. We demonstrate that, when the Fermi energy of the graphene disk is 0.6 eV and the incident light wavelength is 8.26 µm, LSPR with compact electric field enhancement is formed. We theoretically calculate the optical forces on the nanoparticles and the trapping potential in the near-field enhancement. The trapping potential generated by the graphene discs in the ON state can cover the adjacent graphene discs. We demonstrate that nanoparticles can be manipulated independently in the x-y plane by modulating the position of the LSPR. Our study shows that the optical force on the nanoparticle is positively correlated with the radius and the relative refractive index of nanoparticles. We investigate the photothermal and thermographic fluidization of our proposed systems, and estimate the forces on the nanoparticles other than the optical force. We consider that the other forces can be neglected under incident intensity I


The as-obtained nanocomposite possesses good hydrophilicity, excellent biocompatibility and high biomolecules loading capacity, which acts as an ideal platform for enzyme modification. Considering this fact, Horseradish peroxidase is expressively immobilized upon Au NPs-PDA-PAA-graphene surface, in order to lay the foundations of a biosensor that is majorly based on enzymatic activity. The biosensor exhibits higher sensitivity towards the determination of H2O2 with linearity ranging from 0.1 μm upto 20 mm, and the limit of detection going down to 0.02 μm. Encouraged by its acceptable electrocatalytic performance, this multicomponent system can also be easily employed for carrying out the real-time tracking of H2O2 coming out of Macrophage cells. Therefore, this work designs an extraordinarily updated platform for biosensing related applications, and also presents a reliable platform for the direct detection of H2O2in vivo and in vitro, which show great potential in bioelectroanalytical chemistry, cellular biology, and pathophysiology.Herein, an Au nanoparticles-polydopamine-poly acrylic acid-graphene (Au NPs-PDA-PAA-graphene) multicomponent nanohybrid is fabricated by surface functionalization of graphene alongside extensive  The structural shape of graphene based nanocomposites incorporated with polymers as well as metallic nanoparticles, and other species to harvest synergetic effects and integrated properties of the individuals, has claimed great interest due to their wide range of scientific as well as industrial implications . Graphenin situ reducing method, Au NPs could easily be distributed upon the surface of the graphene nanosheets in a homogeneous way. The resulting Au NPs-PDA-PAA-graphene nanocomposites work an ideal platform for the modification of biomolecules. Horseradish peroxidase (HRP), with this unique ability of catalyzing the oxidation for an ample amount of substrates via hydrogen peroxide or any other closely related components, is hailed as a mainstream tool metalloenzyme for establishing the electrochemical biosensors  was added. Later, the prepared mixture was stirred at 40°C for 36 h. Then, CH2Cl2 was removed by centrifugation, and sediment was washed thoroughly by acetone and water to get pure PAA-graphene.The preparation of PAA-graphene: The synthesis of PAA-graphene was performed by hydrolyzing poly tert-butylacrylate (PtBA). The synthetic procedure of PtBA-graphene was described in our previously published paper . Brifly,2CO3 solution was poured to adjust the pH to 8.5. After sonication for 0.5 h, the solution became homogeneous. This solution was then transferred to an ice-bath, and followed by the addition of N-Hydroxysuccinimide  and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride , the mixture solution (denoted as solution A) was made to stir under N2 for about 15 min. Meanwhile, Na2CO3 (55 mg) was dissolved in 10 ml of deionized water in order to prepare solution B. This solution was also made to stir under N2 for about 15 min, and then dopamine HCl (240 mg) was poured in with yet another degassing for about 15 min. Later, solution B was mixed with solution A and was again stirred for about 30 min inside an iced-water bath for about 12 h at around 35°C. During this process, dopamine is easy to polymerize to form polydopamine in alkaline conditions. Eventually, the reaction mixture was made to centrifuge and was also washed thoroughly using deionized water to achieve PDA-PAA-graphene.The synthesis of PDA-PAA-graphene: PAA-graphene (200 mg) was dissolved in 10 ml of deionized water, Na4 solution (50 mm). The reaction was allowed to continue overnight at the expected room temperature. At the end of the reaction, the Au NPs deposited PDA-PAA-graphene was removed from the suspension via centrifugation process and were frequently washed with water.The preparation of Au NPs-PDA-PAA-graphene: PDA-PAA-graphene (10.0 mg) was put inside a reaction vessel, and was poured with 10 ml of HAuCl−1 HRP for overnight reaction, followed by washing with Milli-Q water and then drying at 4°C.The enzyme based electrode was designed by immersing Au NPs-PDA-PAA-graphene electrodes into phosphate buffer solution (PBS) with 0.2 mg ml2O as solvent. UV-vis spectra were observed on a Schimadu UV-2550 spectrometer. Scanning electron microscopy images were acquired by using FESEM instrument . CV and chronoamperometric analysis were undertaken by a CHI 660 D electrochemical workstation (CH Instrument Company). For this purpose, a traditional three-electrode system was selected. HRP/Au NPs-PDA-PAA-graphene electrode was used as a working electrode. The auxiliary and reference electrodes were Pt wire and Ag/AgCl, respectively. All the measurements were conducted at room temperature.A Kratos-Axis spectrometer having monochromatic Al KR of , an X-ray radiation of (15 kV and 10 mA) and a strong hemispherical electron energy analyzer, was used to carry out X-ray photoelectron spectroscopy (XPS) determinations. Casa XPS software was employed to accomplish curve fitting and background suppression. Fourier-transformed infrared spectrum (FT-IR) was observed on Perkin Elmer FTIR. Thermogravimetric Analysis (TGA) was achieved with the help of TA Instruments TGA/DSC. 1H NMR measurement was performed on a Bruker AVANCE NEO 400 M equipment with D® is a modified MCDB 131 formulation and is supplemented with 10 μg/ml hEGF , 1.0 mg/ml Hydrocortisone, 50 mg/ml Gentamicin, 50 μg/ml Amphotericin B, 3 mg/ml Bovine Brain Extract (2 ml), 2% v/v Fetal Bovine Serum (FBS) and stored at 37°C in humid conditions with 5% CO2. 24-well plate was used to seed macrophages where they gained 80% confluency before experiments. Calcein-AM was used for living cell staining. Macrophages cells were incubated at 37°C for 15 min before imaging.ATCC (United States) supplied the macrophages and the cells containing Bovine Brain Extract (BBE) supplement were stored in Endothelial Cell Growth Medium (EGM). EGMvia the condensation reaction between the NH2 group in DA and the carboxyl group in PAA, meanwhile, DA will polymerize to form polydopamine (PDA) in alkaline conditions. Next, Au NPs are immobilized onto PDA-PAA-graphene by in situ reducing of HAuCl4 by dopamine. Au NPs-PDA-PAA-graphene was coated on the glassy carbon electrode to build a platform for enzyme loading. Finally, HRP was absorbed on the electrode to construct an enzyme electrode.The detailed process employed for carrying out the preparation of the Au NPs-PDA-PAA-graphene composite is illustrated in 7/2 and Au 4f5/2 show up at the binding energies of 83.9 and 87.7 eV respectively  is first applied to trace the synthesis process. The condensation reaction between dopamine and PAA-graphene can be verified by noticing a new absorbance peak at 400.8 eV linked to the binding energy of N1s in an XPS spectrum of PDA-PAA-graphene . After iectively , suggestvidually   in PDA-PAA-graphene. Where, A stands for the integral part of the peaks at d 6.83–6.40 representing the quantity of H in the aromatic rings of the given catechol moieties, while A0 corresponds to the integral part of the peaks at d 2.2–1.2 showcasing the quantity of H in the PAA backbone. The dopamine ratio found in the resultant polymer is nearly 25% as per the given method. This result is a little lower than that calculated by thermogravimetric analysis (31%)  .4, a relatively new peak at 556 nm appears and the solution becomes violet black in color. This newly appearing peak can well be stemming from the surface plasmon resonance (SPR) absorptive band for Au NPs, highlighting the reducibility of AuCl4−1 to Au NPs in a successful way . A clearly distinguishable couple of redox peaks in the CVs of HRP/PDA-PAA-graphene are attributed to the FeIII/FeII redox coupling related to the heme protein for HRP  and anodic peak potentials (−0.267 V). Considering the conventional potential [Eo’ = (Epa + Epc)/2] of −0.294 V, and peak point separation (ΔEp) ∼53 mV at the scan rate of (50 mV/s), indicating a reversible electrochemical behavior of HRP, which is much better than other HRP-based biosensors known so far  and Faraday’s law, the electrochemically active HRP can be calculated from HRP/Au NPs-PDA-PAA-graphene surface from the equation.    ], 3-mercol cm−2) .2O2 has been used as an analyte to study the catalytic applications of the fabricated HRP/Au NPs-PDA-PAA-graphene films. 2O2. When the different concentrations of H2O2 were injected into PBS, there was a clear rise in the reduction peak current with a gradual decrease in the oxidation peak current. This phenomenon well explains the remarkable electrocatalytic process for the HRP oxidation via H2O2 which in turn was reduced. H2O2 oxidized the HRPre to HRPox which was further reduced through electron transfer upon the electrode surface. As H2O2 concentration increased it encouraged a large cathodic peak current value, in turn there was a fast rate of electron transfer between the quantities of electrode surface and immobilized HRP.H2O2 in PBS at −0.32 V is shown in 2O2 concentration and attains a steady state within 5 s, which is credited to the rise in electron transfer from the embedded Au NPs. The lowest limit of detection (0.02 μM S/N = 3) and an excellent linearity range from 0.1 μm to 20 mm (R = 0.999) is better than that in similar systems previously reported  of ∼3%. Furthermore, the RSD for the current responses for more than 10 sensors obtained by following the similar protocol is ∼5%. For the stability evaluation of the HRP/Au NPs-DA-PAA-graphene film electrode preserved at 4°C, it gives 90% response even after 2 months of refrigeration  has been observed on the HRP/Au NPs-PDA-PAA-graphene film electrode at the applied potential (−0.32 V), which then further decreases as the H2O2 scavenger catalase was spiked. The same procedure was carried out with control well plates (without macrophages) which showed no response as depicted by 2O2oxidation. All the above discussed results markedly validate that the as-fabricated biosensor can initiate a new opening in biosensing platforms for the unswerving determination of extracellular as well as intracellular H2O2 and could well be effectively helpful for advanced physiological and pathological related studies.By keeping in mind all the advantages of the excellent catalytic performances of the fabricated electrode such as lowest limit of detection, enhanced sensitivity, and quick response, it is noteworthy to say that the as-fabricated biosensor can be used for the determination of the extracellular Hst cells . Howeverst cells . The che healthy . Accordi2O2 detection. The biosensor exhibits remarkable results in terms of extraordinary sensitivity, wider linear range (0.1 μm–20 mm), noble stability, lowest limit of detection (0.02 mm), and reproducibility for H2O2 detection, which is superior to previously constructed biosensing podiums. Hence, this work brings up an advanced biosensing platform for the determination of H2O2in vivo and in vitro, which can be of utmost advantage for bioelectroanalytical chemistry, cellular biology, and pathophysiological studies.In summary, new Au NPs-PDA-PAA-graphene composite films have been synthesized by loading highly active enzyme immobilization. The material is introduced onto the electrode surface, and serves as biosensor for extracellular and intracellular H


Semiconductor photoconductive switches are useful and versatile emitters of terahertz (THz) radiation with a broad range of applications in THz imaging and time-domain spectroscopy. One fundamental challenge for achieving efficient ultrafast switching, however, is the relatively long carrier lifetime in most common semiconductors. To obtain picosecond ultrafast pulses, especially when coupled with waveguides/transmission lines, semiconductors are typically engineered with high defect density to reduce the carrier lifetimes, which in turn lowers the overall power output of the photoconductive switches. To overcome this fundamental trade-off, here we present a new hybrid photoconductive switch design by engineering a hot-carrier fast lane using graphene on silicon. While photoexcited carriers are generated in the silicon layer, similar to a conventional switch, the hot carriers are transferred to the graphene layer for efficient collection at the contacts. As a result, the graphene-silicon hybrid photoconductive switch emits THz fields with up to 80 times amplitude enhancement compared to its graphene-free counterpart. These results both further the understanding of ultrafast hot carrier transport in such hybrid systems and lay the groundwork toward intrinsically more powerful THz devices based on 2D-3D hybrid heterostructures. THz imaging and spectroscopy always request even more efficient components. Here the authors, thanks to a modified photoconductive switch that includes a graphene layer, demonstrate a high-speed photoconductive switch without sacrificing the generated power. A THz PCS is composed of two metal pads contacting a semiconductor channel , typically composed of GaAs, InP, or silicon with high defect density. When operated as an emitter, a PCS is voltage-biased and illuminated with ultrafast femtosecond laser pulses. Electron–hole pairs are excited in the channel and separated by the bias field, creating a transient current. The transient current decays rapidly due to the sub-picosecond relaxation of excited carriers in the heavily defective semiconductor channel. The transient current in PCS couples with a THz antenna to emit the THz signal to the far field. While substrates with longer carrier lifetime (such as semi-insulating GaAs) can be used for efficient broadband THz emitter through clever engineering (such as the use of interdigitated antenna)7, short carrier lifetimes (picosecond) are in general preferred for efficient THz generation when the PCS is coupled with transmission lines/waveguides for THz modulation, studies of device transient phenomena, or almost any other application employing confined fields. The early work on PCS showed very low conversion efficiency for converting pump intensity to THz field9. The reason is a tradeoff between speed and amplitude: to enable sub-picosecond carrier lifetime, the channel materials are made defect-rich with either low-temperature growth or ion implantation. As a result of increased scattering, the carrier mobility drops substantially12, typically to around 1–200 cm2 V−1 s−1. The low mobility prevents the excited carriers from traveling a long distance before recombination, leading to a small transient current and weak THz emission. To mitigate this problem, researchers employ interdigitated15 and nanostructured plasmonic19 metal contacts. These designs reduce the carrier transport path length and increase absorption near the contact, making the carrier separation more efficient. However, they all require substantial surface patterning with sub-micrometer feature sizes, increasing the fabrication complexity.The photoconductive switch (PCS) is an important and widely used technology in pulsed THz field generation and detection, making it a critical building block in THz imaging and time-domain spectroscopy applications2 V−1 s−1 when suspended and 60,000 cm2 V−1 s−1 when encapsulated by hBN at ambient temperature21. It has been shown that hot carriers in graphene relax within a few picoseconds24, orders of magnitude faster than in conventional defect-free semiconductors. These features make graphene an exciting platform to study ultrafast hot carrier dynamics and THz generation. THz emission has been reported on graphene devices with a suspended graphene–metal interface due to built-in electric fields and photo-thermoelectric effects25. Other work has shown THz emission due to photoconductive effects26 and thermally excited plasmons27. However, all these approaches showed a rather low efficiency due to the low optical absorption  illuminates the metal–graphene–silicon heterostructure. The ultrafast hot carrier transport generates a THz field which is then coupled to the coplanar waveguide. After 100 μm propagation, the signal reaches the second Auston switch functioning as the detector. The detector switch is opened by a time-delayed probe pulse to enable sampling of the transient THz field. We tune the time delay of the pump and probe (or “gate”) beams via a motorized delay line  is applied across the graphene channel. A higher voltage up to 45–105 V is possible given the high breaking field of graphene with optimized sample preparation and 9 V We first directly compare the performance between our graphene–silicon hybrid PCS and silicon PCS with identical design except for the top graphene layer. Figure 38. We derived the values by fitting the rise slopes and fall slopes in Fig. We then measured the bandwidth from hybrid PCS with both the width of fitted Gaussian peaks Fig.  and Fourvel Fig.  due to g41 and local built-in field effects.Next, we investigated the possible mechanisms contributing to the large enhancement of THz generation in the graphene–silicon hybrid PCS. The generated THz field’s amplitude linearly increases for larger channel bias  model, as depicted in Fig. 2O3 as gate dielectrics) on top of the hybrid PCS structure  current at the more positive gate bias (Vg) is suppressed heavily. Similar behavior was observed on all 8 devices characterized  and sweeping the gate bias and the beam spot position along the channel  geometries. Ultrafast measurements on nanoelectronic devices, ballistic conductors, high-speed on-chip switching devices, etc. are often best-performed on-chip.By engineering a hot carrier fast lane in graphene–silicon hybrid PCS, we demonstrated significant enhancement of THz field amplitude without sacrificing bandwidth or SNR. Our investigation supports that photocarrier generation mainly happens in the silicon layer; hot carriers are then transferred from silicon to the graphene layer via CT mechanism and use graphene as the hot carrier fast lane to the metal contacts. Despite the earlier envisions of weak THz emission in graphene-based devices+ ions at 100 keV with a flux of 1015 cm−2. The ion-induced defects work as recombination centers. Previous studies reported that the excited carrier lifetime reduces to around 0.7 ps50 at our implantation flux, as verified by time-resolved reflectivity measurements. A CVD-grown graphene layer is then wet-transferred to the substrate and patterned into aμ graphene channel  using photolithography and oxygen plasma etching. Finally, a 300-nm-thick layer of gold is deposited onto the sample to form both metal contacts and double-stripe THz waveguides45 using standard lithography and lift-off processes.The device was fabricated on a silicon-on-sapphire substrate, with a silicon thickness of 300 nm. The silicon was first damaged by ion implantation with O50.The lifetime of transient carriers in silicon Auston switch is characterized by the same on-chip pump–probe measurement with an identical layout to our main measurements, with the only difference being that the emitter does not have a graphene layer on top. Supplementary Fig. Supplementary InformationPeer Review File


The as-prepared rGO-TPEP not only has good dispersion in solution but also processes the AIE feature. Its fluorescence intensity is 2.23 times higher than that of TPEP at the same condition. The unique optical properties and AIE effect enable the rGO-TPEP as a chemical sensor for highly sensitive explosive detection in aggregated state and solid state. In the aggregated state, trace 2,4-dinitrotoluene (DNT) can be detected by the rGO-TPEP even when the concentration is as low as 0.91 ppm, and the quenching constant is as high as 2.47 × 104 M-1.In this work, a dispersible graphene-based material with a characteristic of aggregation-induced emission (AIE) was prepared by wet chemical reduction of graphene oxide (GO). During the GO reduction process, a conjugated molecule TPEP containing tetraphenylethylene (TPE) and pyrene was employed as a stabilizer because of the  However, the performance of graphene is dependent on its dispersion in practical application. The graphene is easy to aggregate due to the strong van der Waals force between the graphene layers  was designed and synthesized, which was used as a stabilizer to prepare the non-covalent functionalized rGO via wet chemical reduction of graphene oxide (GO). The as-prepared rGO-TPEP not only had good dispersion in solution but also processed the AIE feature. Compared with TPEP, the AIE effect of rGO-TPEP was greatly enhanced. Furthermore, rGO-TPEP can be used for the detection of explosive as low as 0.91 ppm, and could be employed as a solid probe for the detection of DNT.2-conjugated structures. The as-prepared rGO-TPEP was stable in THF after removing the insoluble rGO via centrifugation. Compared with TPEP, rGO-TPE displayed a more transparent color, revealing less rGO in rGO-TPE than that in rGO-TPEP. Without conjugated molecules, rGO was only stable for several minutes, presenting its poor dispersion in THF solution. Therefore, TPEP is a better stabilizer for functionalized rGO due to the π–π interaction between rGO and TPEP.As illustrated in -1 were ascribed to the hydroxyl, carbonyl groups, and C=C skeletal vibration, respectively , 2,4-dinitrotoluene (DNT), and picric acid (PA). They not only pose a threat to the security of the country and society but also pose serious health hazards to human body. The explosive sensor based on photoluminescence (PL) has attracted extensive attention because of its high sensitivity. Explosives can cause fluorescence quenching of electron-rich probes through the photoinduced electron transfer (PET) mechanism . However0/I) and DNT concentration (2) was 0.95315, and the quenching constant was 2.47 × 104 M-1. In the concentration range of 50–250 µM (9.1–45.53 ppm), the quenching constant was 5.71 × 103 M-1. The higher value of quenching constant in the lower concentration means higher sensitivity and accuracy of detection for a small amount of explosives, so rGO-TPEP is more suitable for the detection of trace DNT.Fluorescence quenching could be detected even when the DNT concentration was as low as 5 µM (0.91 ppm), and the degree of quenching increased with the increase of DNT concentration . In the ntration , when DNIn addition to the aggregated solution state, it can also be detected in the solid state, which is even more convenient. The filter paper was dipped in the rGO-TPEP solution and dried to get the test paper. When the paper was dipped in explosive solution, it could be seen that the luminescence of the filter paper (right picture) was significantly weakened, while the fluorescence effect of the filter paper not soaked by DNT was very strong. This confirms the prepared rGO-TPEP could also be used as a solid probe in real application. It can be seen that the luminescent graphene has a good application prospect in explosion detection.In conclusion, non-covalent functionalized graphene was designed and prepared based on the π−π interaction between graphene and TPEP via the wet chemical reduction of GO. The as-prepared rGO-TPEP not only had good dispersion in solution but also processed the AIE feature. Compared with TPEP, the AIE effect of rGO-TPEP was greatly enhanced. Furthermore, rGO-TPEP could be used for the detection of explosive as low as 0.91 ppm and could be employed as a solid probe for the detection of DNT. These results offer new opportunities for developing new graphene-based materials with promising applications in chemical sensors, optoelectronic devices, and biomedicine.