We revealed lower total and daily functioning score in female group. Further analyses stratified by sex and activity of the disease presented many significant differences between the groups, revealing important issues for the discussion about gender specific differences in the HRQL of patients with sarcoidosis. In spite of clinical presentation may be similar, expectations and main concerns of sarcoidosis patient can vary between females and males. Therefore, it appears that in terms of education and symptomatic treatment accents should be put differently depending on the gender of the patient. Our results may also point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.Sarcoidosis is granulomatous disease, which complex etiology is yet to be fully discovered. In the majority of cases its course is self-limiting. However it can have different clinical manifestations and can be debilitating condition with great impact on health-related quality of life (HRQL). The aim of our study was to assess if there are any differences in HRQL dependent to gender. We examined a group of 33 males and 42 females (with no differences in mean age, disease activity, TLCO, FEV In over 90% of patients intrathoracic lymph nodes and/or lung parenchyma are involved2. This is important because it serves to improve understanding about the patient’s perception of how disease and treatment affect their overall satisfaction with life in various different areas of functioning3.Health-related quality of life (HRQL) has become a crucial element of evaluation in modern patient-oriented approach to decision making in medicine. This model is especially important when treating patients with sarcoidosis as the disease itself is rarely life-threatening, and the physiological impairment is usually not severe. Therefore, each decision with regards to treatment should be considered in the context of balance between medicinal benefits and quality of life. Further, HRQL assessments facilitate patient-physician communication5, but interestingly, also tend to present less advanced radiographic stages6. There are also differences in organ involvement—women more frequently suffer from skin, eye, liver and peripheral lymph node involvement8. Also, manifestations of Löfgren's syndrome differ between men and women, with erythema nodosum found more often in women, whereas a marked periarticular inflammation of the ankles or ankle arthritis without erythema nodosum is seen primarily in men7.Although gender affects epidemiology, pathophysiology, manifestation and treatment of a broad range of diseases, gender-specific oriented healthcare approach seems to still be neglected. Sarcoidosis is one of the diseases where gender plays an important role. Women more frequently suffer from sarcoidosis9. Therefore, it is not surprising that gender, among other various factors, significantly influences HRQL. However, despite increasing evidence that points to the importance in the understanding of this field, knowledge about gender differences specific to HRQL in sarcoidosis patients is still relatively scarce.Two genders manifest significant biological, behavioral, social and cultural differences. Sex differences are also visibly reflected in social conditions, lifestyles, health perception, and health care behaviorsThe purpose of our study was to identify associations between gender and HRQL scores using the Sarcoidosis Health Questionnaire (SHQ). The target of our study was not only limited to the three main domains described by this tool , but also focused on the results of individual questions which, when analyzed separately, may lead to important clinical conclusions.This study is a single institution, prospective analysis of patients admitted to the Department of Pneumology and Allergy of the Medical University of Lodz or the adjacent Outpatient Clinic. The study procedures were approved by the Ethical Committee for Human Studies of the Medical University of Lodz. All study participants gave informed written consent to participate in the study. The study was performed in accordance with the Declaration of Helsinki.All study participants were non-smoking, adult Caucasians with a confirmed (in the past as well as newly made) diagnosis of sarcoidosis. The diagnosis was based on histopathological examination or on typical clinical and radiological findings—Lofgren’s syndrome, chest CT suggestive of sarcoidosis supported by additional test results  after exclusion of other conditions. To avoid potential skewed results, we did not enroll patients dealing with any significant stressful life situation that was not related to their health status .We excluded patients with any other pulmonary or autoimmune disease as well as patients with confirmed extrapulmonary sarcoidosis of the heart, central nervous system, skin and/or eyes. Other form of extrapulmonary sarcoidosis  did not exclude the patients. We also excluded patients with acute coronary syndrome, severe heart failure (NYHA III and more), chronic kidney disease, any previously diagnosed mental illness and/or a history of malignancy in their past medical history.As a potentially significant cofounding factor, we also excluded patients currently receiving oral steroids or other medications for sarcoidosis other than non-steroid anti-inflammatory drugs and other painkillers.Patients were divided into study subgroups according to gender and disease activity, into active and inactive sarcoidosis group. Inactive sarcoidosis was diagnosed when complete radiological and clinical resolution was achieved or when radiological stabilization was noted in a patient without other signs or symptoms of pulmonary or extrapulmonary disease. Active sarcoidosis was diagnosed when one of the following criteria was met: present symptoms of pulmonary sarcoidosis , Loefgren syndrome and up to 3 month after, signs of extrathoracic sarcoidosis, radiological progression or worsening of the lung function tests, increased percentage of lymphocyte in broncho-alveolar lavage fluid, hypercalcemia or hypercalciuria.10. This is a short, self-administered questionnaire for persons with sarcoidosis of varying disease burden and organ involvement11. SHQ is a comprehensive measure analyzing three domains: daily functioning, physical functioning, and emotional functioning. Each domain is assessed by questions related to its characteristics, scored from 1 to 7. Then, scores were calculated according to the equation presented by the authors of the questionnaire11.To measure HRQL we used the validated Polish version of the SHQContinuous data were presented as mean with standard deviation (SD) or median with interquartile range (IQR) from LQ (25%) to UQ (75%), depending on the data normality. Variables were compared using the unpaired Student’s t test, Welch t test or the Wilcoxon rank sum test with continuity correction, depending on data normality and homogeneity of variance. The correlation analysis was performed using Spearman’s test.Categorical data were presented as absolute value and percentage. Such data were compared using Pearson’s Chi-square test (with Yates correction if appropriate) or Fisher’s exact test concordantly with test assumptions.https://www.R-project.org).Analysis was performed using R software  females and 33 (44%) males. Characteristics of study participants are presented in Table P = 0.14), sarcoidosis activity (P = 0.33), and presence of active Löfgren’s syndrome (P = 0.86). There were no between gender differences according to pulmonary function test results: TL,CO (P = 0.86), FEV1 (P = 0.48), FVC (P = 0.96), and FEV1/FVC (P = 0.95).Female group and male group did not differ according to age (P = 0.02). Analysis of individual domains revealed a significant difference only in physical functioning: 4.28 vs 4.87 (P = 0.02). However, in detailed analyses we found significant differences in questions from all domains as follows: “felt bodily pain” (P = 0.006), “bothered by sarcoidosis skin or hair problems” (P = 0.0005), “bothered by eye or eyesight problems” (P = 0.02), “had joint pains” (P = 0.02), “been bothered by headaches” (P = 0.0008), “worried about the amount of pain and discomfort” (P = 0.047) and “felt satisfied with the appearance of your body” (P = 0.049). All results of detailed analysis are presented in Table We found a significantly lower total SHQ score in the female group—4.64 vs 6.14 P = 0.0. AnalysiWhen the subgroups depending on disease activity, not gender, were analyzed, some associations with SHQ results were found. In active sarcoidosis, there were significantly lower scores for daily functioning, but not for physical functioning and total score Table .Table 3DFor individual questions, there were significant differences in the following questions: “Felt you were full of energy”, “Felt your breathing was completely comfortable during your normal daily activities”, “Worried about the amount of pain and discomfort”, “Felt that everything you did took a lot of effort”, “Felt that your physical problems interfered with your social activities when with family and friends”, “Felt that you accomplished all that you wanted”, “Felt bodily pain”, “Felt that your emotional problems affected your relationships with family, friends, or coworkers”, “Felt sarcoidosis controls your life”, “Had a good night’s sleep”, “Felt confidence in yourself and your abilities”, “Felt you were as healthy as others your age”, and for “Been discouraged by physical limitations in performing your normal daily activities or your job” Table .Then, we compared both sexes within active and non-active sarcoidosis group. In the female active sarcoidosis group we observed significantly lower scores for the following questions: “Been bothered by headaches”, “Bothered by sarcoidosis skin or hair problems”, “Felt discouraged by recent weight gain”, “Felt bodily pain”, “Felt satisfied with the appearance of your body”, but not for any of the main domains. Among female patients with non-active sarcoidosis, we noticed lower scores for physical functioning and for the following questions: “Been bothered by headaches”, “Felt bodily pain” and “Experienced wheezing” Table .Table 4DWe made also similar analysis for the genders separately, noticing that the active period of sarcoidosis influences SHQ in men and in women in different aspects. Namely, female patients with active disease had a lower score for daily functioning and a lower score in the following questions: “Bothered by sarcoidosis skin or hair problems”, “Worried about the amount of pain and discomfort”, “Felt that your physical problems interfered with your social activities when with family and friends”, “Felt that your emotional problems affected your relationships with family, friends, or coworkers”, “Felt satisfied with the appearance of your body”, “Felt you were as healthy as others your age” and “Been discouraged by physical limitations in performing your normal daily activities or your job” Table .Table 5SOn the other hand, male patients with active disease had lower scores for daily and physical functioning. When particular questions were analyzed, differences were found in following: “Felt your breathing was completely comfortable during your normal daily activities”, “Felt shortness of breath walking upstairs, the length of a city block, or up a small hill”, “Had a good night’s sleep”, “Experienced wheezing”, “Felt confidence in yourself and your abilities”, and “Felt you were as healthy as others your age” Table .12. Authors did not analyze individual elements of the questionnaire, but instead, analyzed pulmonary function tests and six-minute walking test results. After this analysis, they suggested that the following factors were associated with poor HRQL differences based on gender: reduction in TL,CO, reduction in 6MWT distance, and an increased sensation of dyspnea. Our groups did not differ significantly with regards to pulmonary function tests.The results of our study showed a significantly decreased HRQL in the female group of patients. In a more detailed analysis, the only domain which was statistically significantly decreased was physical functioning. This result is concordant with a previous study by Bourbonnais et al.worried about the amount of pain and discomfort and were more discouraged by physical limitations in performing their normal daily activities or job. On the other hand, active disease in male patients affected daily functioning as well as physical functioning domain. In particular questions analysis, we observed different pattern of answers. Notably, significant differences were observed in questions related mainly to somatic health  and self-confidence. When we analyze Table After stratification by sarcoidosis activity, we noticed that in the active sarcoidosis group, the sexes did not differ according to any main domains, but females had significantly lower scores concerning headaches, skin or hair problems, gaining weight, body appearance and bodily pain. However, in non-active sarcoidosis group the differences in the physical functioning appeared—women had significantly lower score in this domain. Similarly to the active sarcoidosis group, females had lower scores for questions concerning headaches and bodily pain when compared to males. Additionally, significant difference in wheezing experience between women and men groups with non-active sarcoidosis could be found. This results (except of bodily pain) present different constellation of answers than baseline stratification by activity within whole study group, revealing new areas for further research and improving communication with patients in everyday clinical practice. We also made similar analysis from another point of view—presenting sexes separately and comparing active and non-active sarcoidosis within these groups. We noticed dissimilar pattern of differences, which is supplementary to previous analysis. Namely, among female patients those with active disease had a lower score for daily functioning than those with non-active. In terms of the questions related to physical appearance, social functioning, and emotional state, women with active sarcoidosis were more After extensive review of the literature of the field, we did not identify a similar study which used our approach and analysis of individual elements of the questionnaire. This is a novel contribution to this field that complements existing knowledge by indicating areas for gender-oriented improvement in the understanding of patient’s perceptions, especially fears about the disease symptoms and prognosis. As a result, this would better facilitate patient-physician communication and, potentially, decrease the level of anxiety, further improving adherence to therapy.Our results can be divided into patients with pattern of answers associated more with pain and discomfort  and those bothered by physical appearance (skin/hair problems), eye or vision problems.16. This includes studies that evidently show a female predisposition to migraine and medication-overuse headache18, justifying our observations. However, despite a clear epidemiological and psychological association, the results indicate the need for an individualized approach to pain treatment and a need to identify the specific needs of female patients in this area. We should also be aware of the risk of medication-overuse in this group and thus, pay more attention towards, firstly, potential complications of NSAID overuse, and secondly, directed at the prevention of this phenomenon.There is a strong body of evidence which documents male and female gender discrepancies in perception of painInformation gathered involving eye and vision problems was difficult to analyze because none of the patients in this study experienced sarcoidosis-related visual symptoms. However, there is a wide range of information on these topics that is readily and publicly available. This information may raise anxiety among patients. As a result, it is important to maintain open channels of communication with the patient regarding issues such as this in order to calm patient’s worries by means of increased education and, in this particular case, regular ophthalmological assessment.7. Therefore, erythema nodosum, affecting esthetical self-esteem, may influence this result markedly. In our study, the number of patients presenting with Löfgren’s syndrome is too low, precluding reliable analysis. However, presented issue indicates that this topic also requires further research.Differences in scores in the question “bothered by sarcoidosis skin or hair problems” would be justified by presence of Löfgren’s syndrome. According to literature of the field, it is important to highlight that females present with different manifestations of Löfgren's syndrome, predominantly with erythema nodosum, while in men more common presentation is periarticular inflammation of the ankles or ankle arthritis without erythema nodosumA relatively low number of patients and a single-center character of study are the main limitations of our research. However, the strict exclusion criteria responsible for a lower number of participants also contributed to a more homogenous study population.Women with sarcoidosis have a lower HRQL score measured by SHQ. This group of patients presents significantly lower scores in questions that attempt to identify the degree of physical functioning impacted by disease.Specific areas connected with lower HRQL are associated with pain and discomfort, physical appearance and eye or vision problems. These results may point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.


A novel capacitive humidity sensor based on carbon black/polyimide composites is presented in this paper. The details of the fabrication, sensor characteristics, and effect of the carbon black additive are described. It was confirmed that the polyimide composite filled with a tiny amount of carbon black was suitable for a humidity sensing dielectric. The humidity sensors with three different dielectrics, which were pure polyimide, 0.01 wt% carbon black/polyimide, and 0.05 wt% carbon black/polyimide, were fabricated by a micro-electro-mechanical-system (MEMS) process. As the amount of the carbon black additive increased, the sensitivity of the humidity sensor increased. The humidity sensor with 0.05 wt% of carbon black had a much higher sensitivity of 15.21%  than that of the sensor with pure polyimide, which was 9.73% (0.1622%/% RH). The addition of carbon black also led to an enhancement in the hysteresis and response speed. The hysteresis of the humidity sensor decreased from 2.17 to 1.80% when increasing the amount of the carbon black additive. The response speed of the humidity sensor with 0.05 wt% of carbon black was measured to be ~10% faster than that of the sensor with pure polyimide. The long-term stability of the humidity sensors was demonstrated as well. Measurement of humidity, the amount of water vapor in air, is very important in many applications, including manufacturing, agriculture, climatology, and biomedical industry . There aFor accurate measurement of relative humidity, various humidity sensors with different sensing mechanisms have been suggested such as capacitive, resistive, electromagnetic, gravimetric, and optical measurements ,4. AmongThe dielectric constant of water vapor is around 80, and a humidity-sensitive dielectric material generally has a much lower dielectric constant. Therefore, absorption of water vapor by the dielectric results in an increase in the capacitance of humidity sensors . DiverseTo develop an improved capacitive humidity sensor, we suggest a carbon-polymer composite, which consists of polyimide and carbon black. Polyimide is suitable as a humidity sensing material because of its linear and large response to humidity and compatibility with the complementary metal-oxide-semiconductor (CMOS) process . In addiIn this paper, we report for the first time a novel capacitive humidity sensor based on a carbon black/polyimide composite. The humidity sensor is designed to have a parallel plate capacitor structure and be fabricated by the micro-electro-mechanical-system (MEMS) process. The characteristics of the developed humidity sensor such as sensitivity, hysteresis, dynamic response, and long-term stability are evaluated accurately by a computer-controlled measurement system. The comparison with the humidity sensor made of pure polyimide is also provided.In order to synthesize the carbon black/polyimide composite, a photodefineable polyimide solution  and carbon black nanopowders with a diameter of 100 nm  were employed. As mentioned above, in this work, the key parameter to achieve the novel sensing dielectric for the capacitive humidity sensor is the amount of the carbon black additive. Tiny amounts of carbon black were added to the polyimide solution to prevent an increase in the conductance of the composite. To verify the effect of the amount of carbon black on the sensing characteristics, three samples with different amounts of carbon black were prepared, which were 0 (pure polyimide), 0.01, and 0.05 wt%, respectively. Undesirable side effects of the carbon black additive on photolithography of the composite can also be avoided with these small amounts. After sealing, the carbon black additive in the composite solution was dispersed by using an ultrasonic bath for 60 h.The humidity sensor was designed to have a parallel plate structure for the measurement of the capacitance. The simplified cross-section of the sensor design is shown in 2 layer was grown was used as a substrate. The bottom electrode with a 300 nm-thick Au film was formed on the substrate by e-beam evaporation and photolithography. A 300 nm-thick SiO2 passivation layer was also deposited and patterned to expose the active region of the underlying bottom electrode. After that, the prepared carbon black/polyimide composite solution was spin-coated for the humidity sensing layer. The coated composite film was patterned by photolithography and was cured in a vacuum curing chamber. After the curing process, the 3 μm-thick carbon black/polyimide composite sensing layer was successfully obtained. At last, for the top electrode, a 300 nm-thick Au film was deposited by sputtering and patterned to have the hole shapes as described in The humidity sensor was fabricated by the MEMS process. For insulation, a 4-inch silicon wafer on which a 300 nm-thick SiOThe measurement system was fully automated and capable of multiple measurements up to 32 samples. The fabricated humidity sensors were wire-bonded to printed circuit boards (PCBs), and the PCBs were connected to a control and switch module . The signal from a selected sensor by the switch was transferred to a precision LCR meter . To control relative humidity, the PCBs were placed in a humidity generating chamber , and the variation of the capacitance of the humidity sensors was measured by using the LCR meter. When measuring the capacitance at each humidity level, to minimize the effect of possible fluctuations of the humidity chamber, ten data points were collected, and the average value was taken. In addition, because capacitance can arise from not only the sensors but also the PCBs, measurement cables, and air, one PCB on which the humidity sensor was not mounted was measured in the chamber to clarify the parasitic element. After that, the parasitic capacitance was subtracted from the measurement results of the actual humidity sensors. Every measurement was repeated at least ten times for a single device to check the reproducibility, and ten devices randomly picked from the same wafer were also verified to eliminate any possibility of errors from fabrication non-uniformity. The schematic of the measurement system is shown in 2 from the sensor output and the regression linear curve. The calculated coefficients of the sensors with 0, 0.01, and 0.05 wt% of carbon black are 0.979, 0.982, and 0.999, respectively. The sensor with 0.01 wt% of carbon black has a slightly higher sensitivity of 10.13%  than that of the sensor made of pure polyimide, which is 9.73% (0.1622%/% RH). The amount of 0.01 wt% of carbon black seems not enough to significantly change the dielectric property of the composite, which results in little difference in the sensitivity. On the other hand, the sensor with 0.05 wt% of carbon black shows a sensitivity of 15.21% (0.2535%/% RH), which is much higher than that of the sensor with pure polyimide. It is known that moisture in the polymer composite can be stored at the interfacial space between the additives and the polymer [The sensitivity of the humidity sensor with a good linearity can be expressed as follows: polymer . The inc.21% 0.25%/% RH, wThe hysteresis characteristic of humidity sensors when water is absorbed and desorbed is very important to measure humidity accurately. The capacitance of the fabricated sensor was measured during a cycle of water absorption (from low to high ambient relative humidity) and desorption (from high to low ambient relative humidity). The hysteresis error can be described as follows:To study the dynamic response of the humidity sensor, the humidity level in the chamber was ramped up and down between 20% RH and three different higher levels, which are 40, 60, and 80% RH, respectively. To evaluate the long-term stability of the humidity sensor, the capacitance was measured and recorded for 100 h at two different ambient conditions: low humidity level (20% RH) and high humidity level (80% RH). In summary, a novel capacitive humidity sensor based on carbon black/polyimide composites has been suggested. There have been efforts to develop resistive-type humidity sensors with carbon-polymer composites of which the conductance is enhanced. However, as far as we know, there have been few attempts to consider the composite as a dielectric for capacitive-type humidity sensors. In this paper, we have successfully demonstrated the possibility of using a carbon black/polyimide composite as a humidity sensing dielectric material to obtain high-performance capacitive humidity sensors. The suggested humidity sensors with polyimide composite filled with tiny amounts of carbon black showed improvements in the sensitivity, hysteresis, and response speed. In the case of the humidity sensor with 0.05 wt% carbon black, a higher sensitivity of 15.21% (0.2535%/% RH) was obtained compared to 9.73% (0.1622%/% RH) for the sensor with pure polyimide, which seems to be due to the presence of the interface between the carbon black additive and the polyimide matrix. In addition, because of the increased contact area with water molecules caused by the carbon black additive, a reduced hysteresis of 1.80% (compared to 2.17%) and a ~10% faster response speed were observed. The long-term stability of the humidity sensors with a small variation was verified as well. Further study exploring humidity sensors with various concentrations of carbon black and the phenomenon at high concentrations to determine the optimal proportion will be the subject of future work.


Non-coding ribonucleic acids (ncRNAs) are a diverse group of RNA molecules that are mostly not translated into proteins after transcription, including long non-coding RNAs (lncRNAs) with longer than 200 nucleotides non-coding transcripts and microRNAs (miRNAs) which are only 18–22 nucleotides. As families of evolutionarily conserved ncRNAs, lncRNAs activate and repress genes via a variety of mechanisms at both transcriptional and translational levels, whereas miRNAs regulate protein-coding gene expression mainly through mRNA silencing. ncRNAs are widely involved in biological functions, such as proliferation, differentiation, migration, angiogenesis, and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. The etiology of IPF is still unclear. Increasing evidence shows the close correlations between the development of IPF and aberrant expressions of ncRNAs than thought previously. In this study, we provide an overview of ncRNAs participated in pathobiology of IPF, seeking the early diagnosis biomarker and aiming for potential therapeutic applications for IPF. IPF is characterized by progressive lung scarring with constantly decreasing the function of the lungs. The prevalence of IPF shows that almost 5 million individuals suffer from this disease worldwide in the United States, and the 3 years and 5 years mortality rates of IPF are at approximately 50 and 80%, respectively . TherefoncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are transcribed from human genome such as message RNAs (mRNAs) but are not translated into proteins after transcription. These ncRNAs directly or indirectly participate in the regulation of multiple functions of intracellular pathobiological processes and affect gene expression by regulating the function of mRNA, DNA methylation, and histone modification and participate in the occurrence and development of lung diseases, thus providing new ideas for the diagnosis and drug treatment targets of diseases ,3,4.2The non-coding RNAs (ncRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), idiopathic pulmonary fibrosis (IPF) were used as keywords searched in PubMed and web of science databases. The papers about reviews, meta-analysis, systematic reviews, books, and documents were excluded. Then, about 85,076 articles from PubMed and web of science databases in the past 5 years (2015–2019)  related 3The articles of ncRNAs and IPF are related in the following three areas: (1) the biogenesis and functions of miRNAs in IPF; (2) the biogenesis and functions of lncRNAs in IPF; and (3) the interaction networks among lncRNAs, miRNAs, and mRNA in IPF.3.13.1.1miRNAs are short single-stranded non-coding RNA molecules found in eukaryotic cells with a length of about 22nt, whose biological processes involve a series of complex steps. The precursor transcripts (pri-miRNAs) are a capped and polyadenylation transcript produced by RNA polymerase II . Then, umiRNAs are involved in many biological processes such as biological development, cell proliferation and differentiation, tissue damage repair, and organ fibrosis and exert a wide range of physiological regulation ,10,11. I3.1.2IPF is one of the most serious fibrotic pulmonary diseases, which commonly afflict the elderly. The main pathological manifestations are the alternation of fibrotic areas with mild or normal pulmonary parenchymal areas which simultaneously occur scar formation and honeycomb-like changes . In shorTo explore the potential of miRNAs as biomarkers of IPF, Li et al.  analyzedIn a recent study, Njock et al.  found thYang et al.  analyzed3.1.3IPF is because of the uncontrolled production of extracellular matrix by fibroblasts in lung injury, which leads to progressive exacerbations and irreversible damages . NumerouAt present, the mature IPF model is BML-induced pulmonary fibrosis model in mice. Zhang et al.  found thThe core pathogenesis of IPF is an abnormal epithelial–mesenchymal crosstalk, which hinders the normal repair process after alveolar damage ,27,28. L3.23.2.1lncRNAs are ncRNAs greater than 200 nucleotides in length. lncRNAs lack coding open reading frames and cannot encode proteins, but they can exert biological functions through interaction with other genetic materials . lncRNAsAlthough lncRNAs are different from other nucleotide sequences and do not have high expression abundance, they are expressed at specific stages of biological development with high tissue-cell specificity and may become biomarkers of various diseases .3.2.2The above has shown that lncRNAs are involved in a variety of biological processes, and substantial evidence suggests that mutations and disorders of lncRNAs may be closely related to the pathogenesis of IPF.Hao et al.  extractein situ hybridization, nuclear isolation, and RNA sequencing have confirmed that lncITPF is located in the nucleus and regulates its host gene ITGBL1 to promote fibrosis by affecting the acetylation of H3 and H4 histones in its promoter region. Then, they studied the upstream and downstream mechanisms of lncITPF in pulmonary fibrosis. The upstream mechanism of lncITPF is mediated by the TGF-β1/Smad2/3 signaling pathway, and the downstream mechanism regulates the acetylation of H3 and H4 histones of ITGBL1 gene by interacting with heterogeneous nuclear ribonucleoprotein L. To assess the potential of lncITPF as a therapeutic target, interfered sequence of lncITPF (sh-lncITPF) was applied to an animal model of pulmonary fibrosis, and the expression of lncITPF in clinical IPF patients was detected. The results showed that the fibrosis indexes of α-sma, collagen, and vimentin in the sh-lncITPF group were lower than those in the control group. The expression level of lncITPF in clinical IPF patients was significantly higher than that in healthy subjects, and the Pearson’s correlation analysis showed that lncITPF expression level was correlated with FVC% predicted. Therefore, lncITPF may become one of the new targets for clinical IPF treatment.Song et al.  first diIn addition, Gao et al.  first di3.3Currently, high-throughput sequencing technology was used to analyze the differentially expressed miRNAs in normal lung tissues and lung tissues of IPF patients, and then GO annotation and KEGG pathway enrichment analysis were used to screen the molecular targets most related to the diagnosis and prognosis of IPF, which laid the foundation for the follow-up clinical transformation therapy. We believe that identifying the diverging interaction network of lncRNAs and miRNAs orchestra and genes will provide important clues for understanding the mechanism of IPF and developing novel diagnostic and therapeutic strategies. At the same time, most of the latest progress of understanding of miRNA and lncRNA regulation in pulmonary fibrosis in the past 3 years are summarized and presented in It has been found that lncRNAs with target sequences similar to miRNAs can regulate the abundance of RNA by isolating miRNAs, or that lncRNAs can directly bind to miRNAs and regulate their functions. Although miRNAs and lncRNAs play an important role in the occurrence and progression of IPF, their regulatory networks in IPF remain unclear. Therefore, numerous studies ,42,43 hain vitro and in vivo experiments further demonstrated that overexpression of PFAL promoted the proliferation, migration, myofibroblastic transformation, extracellular matrix deposition, and fibrosis of lung fibroblasts by modulating miR-18a. On the contrary, the above fibrosis indexes were all decreased after the PFAL was knocked out. Further, they studied the intrinsic mechanism and showed that PFAL played the role of an endogenous RNA, competitively binds to miR-18a, and inhibits its expression and activity, thereby promoting lung fibroblast activation and fibrosis. In addition, they found that knock-out of miR-18a resulted in fibrosis of lung fibroblasts, whereas its overexpression reduced TGF-β1-induced pulmonary fibrosis. At the same time, the expression of miR-18a was decreased in patients with IPF by RT-PCR. Therefore, they believe that by knocking out PFAL and then regulating the expression of miR-18a, it may become a new treatment for pulmonary fibrosis.A recent study  showed tLiu et al.  found thhttp://starbase.sysu.edu.cn) and verified by dual-luciferase reporter assay. The results showed that miR-196a was a target of H19 in IPF. COL1A1 is a known target gene of miR-196a. To explore the relationship between H19, miR-196a, and COL1A1, they found that the expression of COL1A1 decreased with the decrease in H9, which could be reversed by microRNA-196a inhibitors. Therefore, they believe that H19 may competitively bind to microRNA-196a to regulate COL1A1 expression. Finally, in vitro and in vivo results have shown that downregulation of H19 attenuates lung fibroblast activation and pulmonary fibrosis, the phenomenon that can be reversed by miR-196a inhibitors. This confirmed once again that lncRNA H19 could promote the expression of COL1A1 through the competitive binding of microRNA-196a and accelerate the process of pulmonary fibrosis. Therefore, they believe that H19 plays an important role in the pathogenesis of IPF, and H19 is one of the directions of IPF gene-targeted therapy.In addition, Lu et al.  took lnc4in situ, and ELISA. Finally, the in vivo or in vitro experiments were conducted to verify the role of target miRNAs, target lncRNAs, and target genes in the pathogenesis of IPF by qRT-PCR, western blot, and transfection. The research model is reasonable, but there are also certain limitations. One miRNA may regulate the expression of multiple genes, and the same gene may be regulated by multiple miRNAs. This phenomenon also applies to lncRNAs. Therefore, this research model can clearly explain one of the modes of action but failed to link the multiple modes of IPF.In most studies, total RNA was extracted from lung tissue or blood samples of IPF patients and normal people, and transcriptome sequencing (including microRNAs and lncRNAs sequencing) was performed ,45. The Further need to demonstrate the correlation between gene expression and disease occurrence. In brief, the safety of gene therapy. For instance, Du et al.  found thIn addition, there is currently no uniform method for miRNA or lncRNA isolation, and the specimens used to extract total RNA mainly come from lung tissue or blood specimens of IPF patients. The extraction methods of these specimens belong to invasive examinations. Moreover, research on biological samples such as saliva and sputum in IPF patients is still less; therefore, the detection of miRNA expression in these samples to diagnose IPF needs further investigation. At present, there is no treatment for IPF etiology or reversal of IPF. The role of ncRNAs in the pathogenesis of IPF requires a lot of research to explore, which provides a new scheme for molecular targeted therapy of IPF.


Gas exposure for 5 min revealed that the presence of nanoparticlesdecorating graphene entail greater sensitivity (13-fold) in comparisonto the bare graphene performance. Noteworthy, excellent repeatability(0.7% of relative error) and a low limit of detection of 491 ppb wereobtained, together with excellent long-term stability. Besides, anextensive material characterization was conducted, and vibration bandsobtained via Raman spectroscopy confirmed the formation of PPy NPs,while X-ray spectroscopy (XPS) revealed the relative abundance ofthe different species, as polarons and bipolarons. Additionally, XPSanalyses were conducted before and after NH3 exposure toassess the PPy aging and the changes induced in their physicochemicaland electronic properties. Specifically, the gas sensor was testedduring a 5-month period, demonstrating significant stability overtime, since just a slight decrease (11%) in the responses was registered.In summary, the present work reports for the first time the use ofPPy NPs decorating graphene for gas-sensing purposes, revealing promisingproperties for the development of unattended gas-sensing networksfor monitoring air quality.Theoutstanding versatility of graphene for surface functionalizationhas been exploited by its decoration with synthesized polypyrrole(PPy) nanoparticles (NPs). A green, facile, and easily scalable formass production nanocomposite development was proposed, and the resultingPPy@Graphene was implemented in chemoresistive gas sensors able todetect trace levels of ammonia (NH In fact, air pollution is linked to severalmillion premature deaths per year.2 Inconsequence, governments and institutions worldwide are trying toovercome this problem that jeopardizes human health and environmentalquality.During the lasts decades,air pollution has become a growing societalconcern since it is associated with global climate change and showsnoxious effects for both our environment and humankind.Natural sources of air pollution such as volcanic eruptionsarenot significant in comparison to those sources derived from humanactivity, such as industrial and combustion processes. However, sincethe replacement of the current energy sources toward renewable onesis progressive, real-time monitoring of the concentration of key pollutantsis needed. With that, it is possible to reveal in space and time whenthe gases reach the TLV, and subsequently, different actions can betaken to reduce both air pollution and human exposure to those health-threateninglevels.3 Inexpensive,yet reliable and accurate enough, sensor devices are key for achievingsuch gas-sensing networks.4 Some techniques,such as gas chromatography coupled to mass spectrometry (GC–MS),show significant drawbacks, as their complicated miniaturization andslow throughput complicate real-time air quality monitoring, despitebeing highly accurate.5 Other approaches,like the use of electrochemical sensors, present lower cost, but miniaturizationand stability issues associated with electrolytes are still a challenge.6 For that reason, chemoresistive sensors haveemerged as a promising option, as they gather many of the requirementsneeded in the next generation of inexpensive gas sensors.7Nevertheless, for achieving a ubiquitous, real-timemonitoringof gases, developing a widespread sensor network possessing some requisitecharacteristics such as inexpensiveness, accuracy, durability, andlow power consumption is needed.8 However,some drawbacks are preventing their effective implementation in commercialdevices. For instance, the selectivity of MOX-based sensors is stillan issue, and usually, high operating temperatures are needed to activatethe catalytic properties of MOX, leading to a high power consumptionand lower durability due to the coalescence of MOX crystals into largerentities, altering their microstructure and, thus, their gas-sensingproperties.9During the last decades, many researchefforts have been focusedon the development of chemoresistive sensors based on metal oxides(MOX). These devices usually show high sensitivity to gases and fastresponse and recovery dynamics, showing the potential for enablingambient monitoring applications.10 Indeed, graphene-basedgas sensors are power lean and require simpler circuitry because thereis no need to use heating elements. Besides, chemical vapor depositionof graphene is becoming a more mature nanotechnology (now can be producedin large quantities at relatively affordable cost) that shows superiorproperties, such as high carrier density and mobility, which is associatedwith low noise levels, and high surface area to volume ratio due tobeing a 2D nanomaterial.11 However, animportant drawback of pure graphene-based gas sensors is their lowsensitivity to gases. For that reason, further graphene modificationsare often needed to improve its gas-sensing properties. The most commonmodifications consist of the direct functionalization of graphene or its decorationwith nanoparticles or nanocrystals .13 However, the creation of a wide variety of graphene hybrids or compositesis also feasible.14 With these approachesit is possible to obtain sensitive, inexpensive, and durable devicesleveraging the high versatility of graphene to being surface functionalized.In consequence, duringthe past few years, graphene has been attractinggreat interest as a gas-sensitive material due to its capability towork at room temperature.3. However,their use usually implies working temperatures of about a few hundreddegrees Celsius.15 Conversely, fewer worksare available for detecting NH3 using carbon-based nanomaterialsat room temperature, probably because of their limited charge transferand, in consequence, poor sensing responses.16 Indeed, carbonaceous nanomaterials like graphene and carbon nanotubeshave been mainly focused on the detection of gases from combustionprocesses, such as nitrogen dioxide,17 withhigher charge transfer than NH3, or even significantlyhazardous ones such as benzene or hydrogen sulfide.18To the best of our knowledge, some nanomaterials such as metaloxides have been widely used for detecting NH3 is35 ppm for 15 min.19 Not limited to this,the significant role of NH3 is well-known in additionalenvironmental problems, such as promoting the formation of particulatematter (PM2.5).20 Therefore,there is a need for commercial gas-sensing devices able to selectivelydetect ammonia. In that way, the present paper combines two nanomaterials,graphene and polypyrrole, which have been demonstrated to show promisefor detecting NH3 at room temperature.22Anthropogenic ammonia is related to industrial livestockproduction,crop agriculture, or fertilizer industries. According to the NationalInstitute for Occupational Safety and Health (NIOSH), the permissibletime weighted average (TWA) exposure limit is 25 ppm for 8 h, whereasthe maximum short-term exposure limit (STEL) to NH23 Specifically,polypyrrole has attracted far more research efforts than other polymersdue to its superior properties such as biocompatibility and biodegradability,high conductivity, easy synthesis, and stability.25 In addition, the PPy morphology has a significant effect on thephysicochemical and electronic properties due to the different arrangementsfound in PPy chains and their associated different charge distributions.In consequence, PPy has been synthesized in a wide range of nanostructures,such as nanoparticles,26 nanoribbons,27 and nanofibers,28 to cite some. These PPy forms are usually synthesized through electrochemicalmethods, in which the pyrrole monomers are electropolymerized in anelectrolyte solution. The main advantage of this method is the highcontrol over the geometry and thickness of the PPy synthesized bymodulating the applied voltage and current density.29 However, its main drawbacks are associated with the relativelycomplex instrumentation and the difficulty of large-scale production.30Functional conductive polymers, such as polypyrrole (PPy),polyaniline(PANI), and poly, probably assemble therequirements to be employed in the next generation of sensors. Theirmain advantages lie in their high sensitivity and their capabilityfor room-temperature operation, large-scale production, and easy integrationin wearable and flexible sensors.3 even under room-temperatureconditions, the first nanocomposite of PPy NPs and graphene as a gas-sensitivelayer presents a significant synergistic effect between the two nanomaterials.This novel approach shows outstanding gas-sensing performance, enablinga highly sensitive, reproducible, and stable NH3 detection,differing from the previously reported use of PPy films combined withdifferent graphene configurations such as graphene oxide and reducedgraphene oxide.32 Besides, the synthesis methodproposed has been revealed as an easy, inexpensive, and scalable tolarge production approach. In addition, the nanomaterial depositionover the sensor electrodes through the airbrush method constitutesa straightforward and fast way that implies high throughputs. Butnot limited to this, the present work presents a green-chemistry approachin which low concentrations of NH3 are detected by usinga solvent-free synthesis procedure and biocompatible nanomaterials.Thereby, it is worth noting that sincepolymers usually lead tosensitive gas detection of NH34 Poly (PVA) (Merck KGaA) was chosen as a water-solublepolymer to act as a dispersion aid. Since previous works already reportedthat greater molecular weights of PVA lead to smaller PPy nanoparticles,35 a PVA with Mw = 186 000 was chosen.First, a 7.5 wt % solution of PVA dissolved in distilled water wasprepared under magnetic stirring at room temperature for 10 min. Afterward,3.5 wt % iron chloride (FeCl3) (Merck KGaA) was added tothe aqueous PVA solution, waiting 1 h to achieve the equilibration.In that time, the solution appearance changed from limpid to orangebecause FeCl3 acts as an oxidizing agent, forming the PVA/ironcation complex. Subsequently, the pyrrole monomer (C4H5N) (Merck KGaA) was added into the aqueous PVA/FeCl3 solution dropwise, with a molar ratio FeCl3/pyrrole of2.5. Then, the solution was kept overnight under vigorous stirringto complete the polymerization. Meanwhile, the appearance changedfrom orange to black, indicating that polymerization took place derivedfrom the contact of the pyrrole monomer with the iron cation. Nevertheless,the resulting nanoparticles should be extracted and cleaned via thecentrifugation method from the solution. Specifically, three consecutivecentrifugation processes (10 000 rpm and 10 min) were conducted,removing the dispersion solution and washing with abundant distilledwater after each centrifugation. The resulting PPy NPs presented theform of a black powder that was dried in an oven at moderate temperature(80 °C).The synthesis of polypyrrolenanoparticles was conducted via chemicalpolymerization, modifying a protocol described in the literature.Afterward, a graphene solution in distilled water(0.5 mg/mL) was prepared by using graphene nanoflakes . Subsequently, to achieve a suitable graphene exfoliation, thesolution was placed in an ultrasonic bath at high frequency (35 kHz)for 1 h. Then, 5% wt of PPy NPs was added to the graphene solutionand immediately mixed under vigorous stirring for 2 h. This methodis based on PPy NPs supported on liquid-phase exfoliated (LPE) grapheneand constitutes an inexpensive, simple, and fast procedure to obtaingraphene nanocomposites with suitable decoration.An additionalgraphene-based solution was prepared to act as areference sample. In this case, a bare graphene solution was preparedand deposited as mentioned above. In consequence, the effect of thesensing performance induced by the presence of PPy NPs can be elucidatedby comparing the sensing results obtained using the reference sample(bare graphene) and the PPy-decorated one (PPy@Graphene).Asit was mentioned before, the PPy NP synthesis and graphene decorationwere conducted using distilled water and room-temperature workingconditions. Furthermore, the products obtained (PPy and graphene)are biocompatible, constituting a green experimental procedure.Figure S1, Supporting Information (SI)]. Subsequently, the gas sensors wereplaced in an airtight Teflon chamber with a volume of 35 cm3. The sensing chamber was connected to a gas mixing and deliverysystem that used calibrated gas cylinders and pure dry air (Air Premierpurity: 99.999%) as carrier. Then, the resistance of the differentsensors was monitored using a multimeter , andresistance changes were recorded while different concentrations ofgases were applied. In order to reduce the power consumption of thesystem and to work under more realistic experimental conditions, thetotal flow was adjusted at a low rate (100 mL/min) using a set ofmass-flow controllers (Bronkhorst High-Tech B.V.) and electrovalves.The sensors were stabilized under dry air for 15 min before beingexposed to a given concentration of a gaseous species for 5 min. Theresponses to several concentrations were recorded by applying successivedilutions of gases and defining sensor response as ΔR/R0 expressed in percentage,where ΔR corresponds to the resistance changesrecorded over 5 min of gas exposure, while R0 is given by the resistance of the sensor in air (or baseline).The resulting graphene nanoflakes decorated with polypyrrole NPswere deposited via the airbrushing method, using nitrogen as a carriergas while the hot plate  was kept at 115 °C.The solution was deposited onto alumina substrates that comprisedplatinum screen-printed electrodes [In order to characterize the gas-sensing performance under a humidatmosphere, a controller evaporator mixer (Bronkhorst High-Tech B.V.)was used to humidify the atmosphere during some of the measurements.With that, the effect of the ambient moisture on sensor response wasevaluated as well.2O3 substrate and ultrasonically dispersed for 20min, at 37 kHz and 100% of power, in a mixture of methanol and water.One drop of the dispersion was then deposited on a lacy carbon filmsupported by a copper grid (300 mesh). Figure S2a, SI) with a size of about 270 × 400 nm2. An imageobtained at higher magnification  . For TEM investigationof bare graphene, the layout deposited was scratched from an AlFigure S2b (SI) shows a narrow nanoparticle size distribution, situatingthe highest frequency in the range from 100 to 120 nm. An AG-Ultra 55 (Zeiss) field emissionscanning electron microscope(FESEM) was used to analyze both nanomaterials separately and theresulting sensitive film. The synthesized PPy NPs suspended in waterwere deposited on a piece of a silicon wafer, showing monodispersednanoparticles 1b. Besid36 This broadening is associated with the scattering of X-raysfrom the PPy chains at the interplanar spacing.37An X-ray diffraction (XRD) analysiswas conducted using a Bruker-AXSD8-Discover diffractometer (Bruker Co.) with a parallel incident beam(Incoated GmbH). The X-ray diffractometer was equipped with a HI-STARgeneral area diffraction system (GAADS) detector from Bruker Co. TheXRD measurement was conducted at 40 kV and 40 mA to generate the CuKα radiation, and the data were collected stepwise over therange 2θ = 5°–70°. The synthesized PPy NPs were also characterized by employing Ramanspectroscopy. The PPy powder was placed onto a piece of a siliconwafer and the analysis was conducted using a Raman spectrometer (Renishawplc) with a coupled confocal Leica DM2500 microscope (Leica MicrosystemsGmbH). The laser employed had a wavelength of 514 nm and the acquisitiontime was set to 30 s, while three cycles or repetitions were acquiredover the spectra to reduce the noise level. 38 A polaron is formed when a π-electron is moved out from theneutral PPy, while a bipolaron can be formed when a second electronis removed. Both forms act as charge carriers along the conductivepolymer.39 Thus, these electron relocationsas polarons or bipolarons induce crystal lattice distortions in thePPy rings.40 Raman spectroscopy for barePPy NPs . These oxidizedstates are associated with intermediate energy levels within the bandgap, resulting in polarons and bipolarons.PPy NPs 2breveal3 configuration (Cα) at 285.3 eV.This type of carbon bonding is associated with sp3 latticedefects and amorphous carbon, being consistent with the low crystallinityregistered for the XRD analysis. The component centered at 284.4 eVreflects photoelectrons emitted from the sp2 carbon configuration(Cβ), which is related to aromatic carbon bonds,whereas the components shifted to higher binding energies are attributedto the C–N (or C–O), C=N (or C=O), andN–C=O (or O–C=O), appearing at 286.5,287.4, and 288.7 eV, respectively. The components related to oxygen-containingfunctional groups , such as carbonyl and carboxylterminations, probably originated during PPy polymerization, in whichthe terminations of the chains can interact with water to form theoxygen groups.43X-ray spectroscopy(XPS) has been conducted to analyze the chemicalcomposition of synthesized PPy NPs using a VERSAPROBE PHI 5000  equipped with a monochromatic Al Kα X-raysource. High-resolution XPS spectra were recorded, accounting foran overall energy resolution of about 0.6 eV. +) and bipolarons (C=N+) at 401.2 and 402.5 eV, respectively. As a result, polaronsare more predominant than bipolarons in the synthesized PPy NPs.The deconvolution of the N 1score level from PPy NPs is depictedin 2 adsorption/desorption results are summarizedin Figure S4 and Table S1 (SI). Specifically,the BET area obtained for bare graphene (730 m2/g) wasslightly higher than PPy@Graphene (644 m2/g). This resultcan be expected since PPy NPs probably present a significantly lowerBET area. Nevertheless, negligible changes in the average pore diametersand pore volumes were observed between both samples, revealing thatthese parameters are mainly ruled by graphene nanoplatelets.Nitrogen adsorption–desorption analysis of bare and PPy-decoratedgraphene was conducted using a Quadrasorb SI surface analyzer (QuantachromeInstruments) for determining the BET (Brunauer–Emmett–Teller)area, average pore size, and pore volume. The samples were degassedovernight at 120 °C before this measurement. The specific surfacearea was calculated through the BET method and the pore size distributionwas determined by the BJH  method. Theobtained N3 was evaluated in similar conditions to those neededin real-time monitoring. First measurements consisted of repeatedresponse and recovery cycles to 25, 50, 75, and 100 ppm of NH3. Figure S5 (SI), showing that graphene decorated with PPy offers up to 7-foldhigher responses  than bare graphene. Besides, since sensitivityis given by the slope of the calibration curves, PPy@Graphene presents14 times higher sensitivity than bare graphene.The ability of the hybrid nanomaterial developedfor detectingNH44 In consequence, both nanomaterials employed, oxygen-defectivegraphene and Cl–-doped PPy, show a mild p-type behavior.When the sensitive layer interacts with an electron-donating moleculesuch as NH3, the hole density is lowered, thus resultingin an increased electrical resistance. According to the experimentalfindings, it can be assumed that bare graphene can interact with NH3 molecules; however, the presence of PPy NPs decorating thiscarbon nanomaterial involves a more intense interaction. In otherwords, the presence of both nanomaterials creates a synergistic sensingeffect, in which graphene and PPy are interacting with the targetgas, thus resulting in superior sensing performance. Besides, bothnanomaterials show a noteworthy interaction through strong hydrogenbonds and π–π-stacking.45 As a result, long-term sensor stability can be attributed to theirefficient interaction.46 In addition, thelarge graphene surface area and its superior electron mobility inducea fast and efficient charge transfer with PPy NPs, leading to an effectivetransduction.47Conjugated polymers are well-known semiconductor materials,whereasPPy stands out due to the high positions of its HOMO and LUMO levels,being easily p-doped and conferring high stability.3 is well-known, especiallyunder room-temperature conditions.48 Inparticular, oxygenated defects and functionalgroups grafted at graphene act as adsorption sites for ammonia molecules,leading a charge transfer toward the sensitive film as follows:The somewhat limitedinteraction between graphene and NH3, thus resulting in better sensing performance. Overall, whengraphene nanoflakes are decorated with PPy, these NPs contribute tothe NH3 sensing through the donation of a lone pair ofelectrons of nitrogen from the target gas to the initially oxidizedPPy, which results in a neutralized PPy through the reduction of theirdoping level, thus decreasing conductivity. Indeed, the ammonia–polymerinteraction is based on a compensation effect, in which the dopinglevel of the polymer chains varies through two reversible pathways.49 The first one is related to an electron transfer,in which the positively charged PPy NPs (PPy+) are reducedto their neutral form (PPy0) when interacting with NH3 molecules, whereas the dopant anion (Cl–) that was compensating the charged PPy+ is reversiblydisplaced as follows:50Nevertheless, PPy NPs tend to show higher interaction with NH50The second feasible sensing mechanism involves a proton transferbetween ammonia, which is a strong base, with the PPy NPs. Specifically,the PPy deprotonation toward ammonia results in the formation of theammonium ion that induces a compensation effect through the dopantanion. Therefore, the doping level is reduced as follows:51 However, graphene decoratedwith PPy NPs showed better sensing performance than bare graphenedespite its lower BET area. This fact is revealing the essential roleof PPy in the NH3 gas detection, enabling a significantelectronic sensitization that compensates this lower specific areaand confirming the importance of the sensing mechanisms proposed.Nevertheless, the mere presence of the nanoparticles cannot explainthe outstanding enhancement in the sensing responses to NH3. Therefore, a synergistic effect between graphene and PPy is probablyheld. For that reason, their interface has been extensively studied.Roughly, both nanomaterials are composed of sp2 conjugatedcarbons resulting in pristine graphene and neutral polypyrrole, showingsemimetallic behavior. Theoretically, pristine graphene is a zeroband gap semiconductor with a tiny overlap between the valence andconduction bands.52 Nonetheless, XPS analysisrevealed that graphene employed in this work shows a significant oxygencontent , which results in p-type doping. This chemical functionalizationand the presence of the sp3 carbon configuration inducea band gap opening in graphene  using a Cary 5000 UV–vis–NIR spectrophotometer(Agilent). Subsequently, the band gap was determined through a Taucplot, in which the gap energy was calculated by extrapolating thelinear portion of the graph between the function (αhν)2 versus the photon energy (eV), as shown in Figure S6b (SI). A relatively wide band gap (3.1eV) for graphene nanoflakes resulted.It is worth notingthat, roughly, greater specific BET areas usuallyled to improved sensing performance owing to a larger area for adsorbinggas species.graphene 5. Indeed53 resulting in poor electronicconductivity. Nevertheless, it is possible to increase the electronictransport by adding new energy levels within this band gap  and the lowest unoccupied molecular orbital (LUMO).Specifically, previous works report a 3.2 eV band gap for PPy in itsneutral state,band gap 5. IndeedEC) relative to the valence bands (ΔEV), owing to the closer levels of valence bandsbetween the two nanomaterials according to XPS analysis.56 Therefore, excitations of the sensitive layertranslate into positive charges (holes) being emitted from the grapheneover the barrier into the PPy NPs. In consequence, near the boundaryof the interface a depletion region can be formed,57 specifically located on the graphene surrounding PPy. Conversely,PPy NPs probably increase carrier concentration, thus being consideredas accumulation regions. As a result, the PPy@Graphene sensing performancewas enhanced because the NPs would have an excess of positive chargesthat can be, to some extent, recombined with the negative chargeswhen interacting with electron donor gas molecules such as NH3. Meanwhile, graphene is lowering its concentration of majoritycharge carriers (holes), further decreasing its conductivity and enhancinggas-sensing response. This fact is worth mentioning considering thatgraphene is mainly acting as a transducer (since limited interactionwith gases cannot be ruled out) while the main gas interaction isprobably located at the PPy NPs, acting as gas recognition elements.Indeed, the potential applied to the transducer element (graphene)is increasing the charge flow and in consequence favoring the holemovement from graphene to PPy NPs over the barrier.3 is a donor of electronic chargewhile the sensitive film is the receptor, the HOMO level of the gasmolecule interacts with the LUMO level of the sensor.583. This electron-donating gas specie is attached to the sensitivefilm via coupling π-bonds.59 As aresult, once the gas donates electrons to the PPy@Graphene layer,the Fermi level in dry air conditions (E0F) undergoes an upward shift, reaching EgF, which results in the lowering of the majoritycarrier (holes) concentration.Considering that NH3. In consequence, once ammonia adsorbs at the hybrid nanomaterial,the energy gap at the interface between the valence band of grapheneand the HOMO of PPy NPs widens , which favors holes from the valence band of graphene totransfer toward the HOMO of PPy NPs. In other words, upon exposureto ammonia, the graphene layer loaded with PPy NPs sees the concentrationof its majority charge carriers (holes) reduced, which translatesinto a significant change in the overall sensor resistance.This shift in the Fermi levelfor graphene and PPy NPs is associatedwith a band-bending readjustment when the sensor is exposed to NH3 in the range of 25–100 ppm and the improvedsensing performance when graphene is loaded with PPy NPs, furthermeasurements at decreased target gas concentrations were performed.The intermediate range of ammonia concentrations ranging from 5 to25 ppm was studied, and results can be found in the Supporting Information. Figure S7 (SI) shows the sensing responses and calibration curves obtained.It is worth noting that this range of concentration has significantinterest for monitoring ammonia in the ambient because it is closeto the TWA and STEL values defined by the agency NIOSH. 3 concentration levels (from 1 to 5 ppm). Even at this range of concentrations,a significant response repeatability and baseline stability was achievedunder room-temperature operation conditions. Conversely, under theseexperimental conditions, the bare graphene sample shows a significantbaseline drift  and poorsensitivity. Indeed, Considering the very low noise levels achieved in the detectionof NH60 In addition,adsorbed water molecules might enhance the proton exchange with theNH3 molecule, inducing a further decrease in the hole concentration,thus leading to higher resistance levels.Nevertheless, the presence of ambient moisture is a key influencingfactor on the gas-sensing performance due to its interfering effect.In consequence, the previous experiments carried out under dry conditionswere reproduced under humid conditions (50% relative humidity at 23°C). However, since thesehigher sensing responses can be beneficialto lower the LOD or improve other sensing parameters, variable relativehumidity levels registered under real conditions of operation canconstitute a significant drawback. To solve that, an alternative mightbe the creation of a sensor array, in which a specific humidity sensoris integrated. Therefore, with the calibration of the PPy@Graphenesensor at multiple ambient moisture levels, this issue could be overcome.y is thestandard deviation of y-residuals and b corresponds to the sensitivity (slope) from the calibration curve.As a result, the PPy@Graphene shows a LOD of 491 ppb for NH3, which is comparable to other types of organic-based nanomaterials.For instance, the use of a conductive sublayer of perfluoro-copperphthalocyanine (Cu(F16Pc) covered by a lutetium bisphthalocyanine(LuPc2) sensitive layer reveals a LOD of 140 and 2000 ppb dependingon if DMBz or TFBz was respectively grafted to the ITO substrate.61 Conversely, Figure S8b (SI) shows a significant baseline drift and poor sensing responsesfor bare graphene samples, denoting the enhancement effect of PPyNPs decorating graphene nanoflakes. Furthermore, cross-sensitivitywas assessed (6H6) and toluene (C7H8). Asa result, negligible resistance changes were obtained toward theseanalytes in comparison to NH3, making the PPy@Graphenegas sensor reliable and promising to detect ammonia in the environment.Considering the gas-sensing results obtained under a humid atmosphere,the limit of detection (LOD) was estimated through the following equation3 pulses for 5 min and recovery steps of 15 min between gas exposures. 3 were also evaluated by reducing the exposure timefrom 5 to 1 min, while the duration of recovery steps was loweredfrom 15 to 5 min . Only a small decrease in response was registered afterthis 5-month period. Nevertheless, to better our understanding, thesensing results were correlated with an XPS analysis performed onsamples freshly synthesized and after 5 months of continuous use,in order to assess aging.Despite these superior sensing properties, a demonstrationof highstability and durability is also required before the potential implementationof this sensor in commercial devices. For that reason, a stabilitytest was performed by measuring and comparing the sensing responsestoward 50 ppm of ammonia for 5 months (3 gassensing (Table S2 (SI)summarizes the relative areas of the different components, showingthe absence of significant differences between both C 1s spectra.Indeed, just a slight decrease in the sp2 configurationcan be observed, while a limited increase in both the sp3 carbon configuration and oxygen content through a higher intensitypeak of C–O/C–N and C=O/C=N is obtained.These results indicate a slight aging of the sensitive film after5 months due to the slight oxidation of the hybrid nanomaterial, demonstratingsuperior reusability and stability. N 1s core levels studied on thePPy@Graphene sample before  and an increase in the C=N defectsof the PPy due to the loss of conjugation during aging . Interestingly, at higher bindingenergy a new component appears when the sensor is exposed to NH3  for a PPy@Graphenesample. The analysis of the O 1s spectrum shows an oxygen contentrelated to the partial oxidation of PPy and the oxygen-containinggroups grafted to graphene. Interestingly, a decrease in the abundanceof the C=O bond was observed while C–O experiences asignificant increase. This fact can be derived from the conjugationof carbonyl groups due to the oxidation of PPy and the interactionwith the gaseous environment.The C 1s core levels were analyzedbefore the NHsensing 10a and asensing 10b. Table before 10c and ae before 10d NH3 sd to NH3 10d. In f3 as an oxidant elementleads to higher stability of electrical conductivity than other oxidantssuch as Fe2(SO4)3 or (NH4)2S2O8.62 The reason is that some anions like SO4–2 tend to experience higher migration to pyrrole nitrogen than Cl– anions, resulting in the quaternization of the nitrogen,thus increasing the PPy degradation and instability. Besides, sincesunlight and operating conditions well above room temperature arewell-known parameters that induce the aging and degradation of PPy,64 the gas-sensing measurements have been conducted under dark conditionsand ambient temperature. Both parameters can be easily implementedin airtight testing chambers, favoring the preservation and stabilityof PPy NPs. Even more noticeably, graphene probably plays an essentialrole in preventing PPy aging thanks to its high hydrophobicity. Whenwater molecules directly interact with PPy chains, the electron densityof nitrogen atoms is changed,65 weakeningthe interaction between the PPy and the dopant anion, in this case,Cl–. As a result, ambient moisture reduces the electricalconductivity of PPy NPs, accelerating their aging. However, the hydrophobiccharacter of graphene may protect the PPy NPs toward their aging derivedfrom the interaction with water molecules. This fact was already demonstratedfor other types of sensitive nanomaterials, such as halide perovskites,in which graphene increases their lifetime and stability toward thepresence of relative humidity in gas sensors66 and solar cells.67Therefore, the low-rate decay of response intensitywith time andits consequent low aging rate could be attributed to several reasons.The PPy NPs synthesis using FeClTable S4 (SI) is summarizingseveral works that report the use of different PPy/graphene hybridconfigurations. Overall, an increase in the sensing performance wasachieved when the PPy is present in the sensitive film. However, essentialinformation is frequently missing, such as the flow rate applied,LOD, and different tests to assess the repeatability, stability, andeffect of the ambient moisture. Table S4 (SI) depicts that graphene nanoflakes loaded with PPy NPs show anoutstanding sensitivity coefficient within the works that report anin situ chemical polymerization. It is worth noting that electrochemicalpolymerization can lead to better sensing responses, since high controlover the thickness and PPy geometry can be achieved. However, theiruse involves more expensive synthesis procedures and fewer possibilitiesfor industrial-scale production. Besides, Table S4 (SI) shows that the present work uses a low flow rate, 10-foldlower than those reported in other works, as well as the use of airinstead of nitrogen as carrier gas. With these experimental parameters,the sensing performance is probably underestimated to some extentbecause higher flow rates or sensing in a nitrogen atmosphere canboost up the resistance changes. But experimental conditions appliedhere are closer to those needed in real-time monitoring of ambientpollutants.Finally, 3 under ambient temperature operating conditions. Thechemical polymerization of PPy NPs offers a low-cost and mass-scalablesynthesis method, resulting in biocompatible nanomaterials with outstandingelectrical properties. Indeed, the development of a chemical resistivedevice able to operate at room temperature paves the way for achievingwidespread air quality monitoring systems due to their simple readoutinterface circuitry, inexpensiveness, low-power consumption, miniaturization,and high portability. Besides, high gas sensitivity and remarkablerepeatability and LOD were obtained for detecting NH3.The sensing mechanisms are probably dominated by electron transfer,in which the presence of PPy decorating the graphene nanoflakes inducesa larger and more effective charge transfer interaction, leading toenhanced sensing properties.A solvent-free, green method was proposedto obtain a graphenenanocomposite loaded with polypyrrole nanoparticles for detectingNHNevertheless, despite the reducedfootprint of this technology,high stability over time is mandatory for gas sensors. In consequence,the sensing properties were assessed for 5 months, and XPS analysiswas conducted to study the aging of the hybrid nanomaterial. Afteran intensive use of the developed sensors, a suitable stability wasobserved. The slight oxidation of PPy observed in the XPS analysisis in agreement with the slight decrease registered in response intensityafter several months of use in humid atmospheres. These results indicatethat these sensors meet many of the specifications for being employedsuccessfully in ambient monitoring applications.Noteworthy,the present work reports the first use of a nanocompositecomprising PPy NPs morphology and graphene, revealing an outstandingsensing performance owing to the significant synergistic effect derivedfrom the integration of both nanomaterials. With all of these, thecombination of both graphene and PPy NPs is paving the way towardlow power consumption and highly durable devices thanks to their capabilityto be operated at ambient temperature. Thereby, the as developed grapheneloaded with PPy NPs shows unprecedented sensing properties, increasingits potential to be employed in commercial devices. However, furtheroptimizing this hybrid gas-sensitive material  will be the subject of future research.