In recent years, the chemical modification of optical fibers (OFs) has facilitated the manufacture of sensors because OFs can identify several analytes present in aqueous solutions or gas phases. Nevertheless, it is imperative better to understand the chemical interactions in this molecular system to generate low-cost and efficient sensors. This work presents a theoretical and experimental study of organic polymeric functionalized OF structures and proposes a cost-effective alternative to monitor breathing and humidity. The device is based on silicon optical fibers functionalized with (3-Aminopropyl) triethoxysilane (APTES) and alginate. The theoretical analysis is carried out to validate the activation of the silicon dioxide fiber surface; moreover, the APTES–alginate layer is discussed. The computational simulation suggests that water can be absorbed by alginate, specifically by the calcium atom linked to the carboxylic acid group of the alginate. The analysis also demonstrates a higher electrostatic interaction between the water and the OF–APTES–alginate system; this interaction alters the optical fiber activated surface’s refractive index, resulting in transmission power variation. The humidity analysis shows a sensitivity of 3.1288 mV/RH, a time response close to 25 s, and a recovery time around 8 s. These results were achieved in the range of 50 to 95% RH. Moreover, the recovery and response time allow the human breath to be studied. The proposed mechanism or device is competitive with prior works, and the components involved made this sensor a cost-effective alternative for medical applications. Human breathing monitoring is nowadays more relevant due to the COVID-19 pandemic. This parameter is related to humidity detection. There is global interest in the development of new devises that make it possible to measure humidity using versatile, economic, and optimized mechanisms.One alternative is humidity optical fiber sensors, which require the functionalization of optical fibers (OFs). This procedure modifies the fiber optic surface and generates a sensitive layer to water absorption; this route alters the refractive index layer . The selHere, bridge molecules are used to connect a selective molecule to the OF. Then, the OF needs to be activated with some labile functional groups that stimulate chemical functionalization. The typical bridge molecule used to modify the silicon derivatives  is , which is depicted in the transversal view in 2. The APTES and the alginate structures were modeled considering only two monomers of each.The chemical interactions of functionalized optical fibers have been studied in the present work through a finite molecular model of the OF, based on the expanded unitary cell of the solid state of SiOThe whole molecules were modeled using Avogadro software . The optFollowing the method mentioned above, we generated an alginate functionalized optical fiber, which was analyzed and validated using scanning electron microscopy (SEM) and in silico assays.The final chemical binding system is depicted in To understand the water adsorption on the OF–APTES–alginate system, a finite model shown in The computed adsorption energy of water on the OF–APTES–alginate surface was −9.85 eV, which indicates that the reaction presented an exergonic behavior, promoting the adhesion of water on the modified OF. Furthermore, to understand the water’s binding mode on the OF–APTES–alginate system, a molecular electrostatic potential surface for this system was calculated see . A polarThe lower concentration of electronic density causes a positive partial charge in the calcium site, which can attract the atom with higher electronegativity in the water molecule, the oxygen, as can be observed in The functionalization of the OF was validated using SEM. The image shows a nanocoating around the optical fiber of a few nanometers, which confirms the APTES–alginate adhesion to the NCF surface using the above method of functionalization, see Once the binding analysis validated the proposed chemical process, a silica No-core Fiber (NCF) was functionalized by the method described above. With the purpose to excite an evanescent field, this fiber was spliced between two segments of Multimode Fiber (MMF); here, the MMF had a core radius of 62.5/125 μm, and the NCF had a total diameter of 125 μm. This optical fiber structure was achieved by an arc splicer, Fujikura FSM-17s, using a multimode program. The total length of the NCF was around L = 70 mm, and this was the sensitive region of our proposed device.The schematic optical fiber structure is depicted in Using a broadband light source, a significant energy interaction between the NCF and the f-layer can be expected. Considering the launched energy, represented by the ray trajectories shown in Hence, when the refractive index of the f-layer is similar to the effective refractive index of the mode involved, the energy outside the NCF will be significant; as a result, the transmitted power output decreases. In contrast, where the f-layer refractive index is below the effective refractive index of the modes involved (water interaction), the deep penetration film decreases; thus, the total transmission power increases. The refractive index alteration can be correlated with the computational simulation results. Here, the charge balance in the molecular systems varied due to the water presence, modifying the system’s electronic structure, and promoting change in the transmitted power. Moreover, the higher interaction between water and OF–APTES–alginate promotes a rupture. Hence, the OF and APTES–alginate chemical interactions are re-stabilized.The schematic setup presented in The humidity analysis was carried out by setting the oscilloscope at 20 mV/DIV and 5 s. Then, the humidity was increased by specific intervals; it is essential to mention that the chamber had a relative humidity of 50% when increasing the humidity and exhibited an average temperature of 25 °C. Here, the humidifier was turned on for 10 s, and then it was turned off; thus, the relative humidity (RH) increased to 60%. Consequently, the voltage signal increased 10 mV. Then, the valve was opened and closed, and the process was repeated until the hygrometer detected an RH close to 75%. Here, the output signal was 60 mV. The process was repeated until the hygrometer detected a high RH around 90%. Here, the maximal output voltage was 140 mV. The relative humidity response is shown in 2 − 8x + 210; this response presents an adjusted R-squared (R2) of 0.9941. It is important to recall that this sensitivity is competitive with some prior works [The analysis was performed several times, and the results are shown in or works ,35,36 anor works ; howeverThe time response (tR) was analyzed by activating the humidifier until the chamber had an RH = 90% see a; here, Once the optical fiber was set into the face shield, a DC reference level (17 mv) was set into the oscilloscope. It is important to consider that the functionalized fiber is bent; as a result, the macro-bending generates a power decrement. The respiratory rate was analyzed by setting the oscilloscope parameters (amplitude and time) at 5 mV and 5 s. Then, the human breath was monitored, and the response is presented in Furthermore, the functionalized optical fiber allows us to detect a long breath-out (Bo) duration of 1.12 s and minimal breath-in (Bi) around 600 ms. The pattern of a regular human breath is shown in Alginate-functionalized optical fiber was theoretically and experimentally validated for humidity and human breath monitoring. The theoretical analysis was performed to understand and validate the binding analysis between alginate and APTES on a silicon dioxide optical fiber surface. The study reveals that water molecules can be easily attracted by the calcium located at the end of the structure. Furthermore, the adsorption energy of water on the OF–APTES–alginate surface was computed close to −9.85 eV, and then an exergonic response can promote the adhesion of water on the modified OF surface. Besides, the in silico assay indicates a polarization effect of the OF–APTES–alginate system; this is related to the calcium atom’s cationic behavior. Consequently, a lower electronic density site can be expected where the calcium is located. Then, water modifies the system’s electronic structure and promotes a change in the transmitted power. This molecule adhesion is also related to the refractive index alteration. We would like to draw attention to the optical fiber sandwich-like structure  that we fabricated, which promoted the interaction between light and the functionalized layer.The total length of the Non-core optical fiber was 70 mm. This material was treated by the chemical process described above, and the humidity and breath monitoring analysis were carried out. The humidity analysis indicated a sensitivity of 3.1288 mV/RH in the range between 50% to 90% RH. Furthermore, the time response was close to 25 s, and the recovery time was around 8 s. These results made this functionalized optical fiber attractive for human breath monitoring. Then, this experimental validation was carried out by setting the fiber on a face shield; here, it was possible to detect human breath monitoring with a signal-to-noise ratio of 12 dB. Moreover, a long breath out of 1.12 s and minimal breath in of around 600 ms were monitored. The proposed structure is competitive with prior works, and the used materials made this sensor a cost-effective alternative for medical applications.


N-acetylglucosamine kinase (NAGK), that synthesizes N-acetylglucosamine (GlcNAc)-6-phosphate, is reported to promote dynein functions during mitosis, axonal and dendritic growth, cell migration, and selective autophagy, which all are unrelated to its enzyme activity. As non-enzymatic structural functions can be altered by genetic variation, we made an effort in this study aimed at deciphering the pathological effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in NAGK gene. An integrated computational approach, including molecular dynamics (MD) simulation and protein–protein docking simulation, was used to identify the damaging nsSNPs and their detailed structural and functional consequences. The analysis revealed the four most damaging variants , which are highly conserved and functional, positioned in both small (G11R and G32R) and large (G120E and A156D) domains of NAGK. G11R is located in the ATP binding region, while variants present in the large domain (G120E and A156D) were found to induce substantial alterations in the structural organizations of both domains, including the ATP and substrate binding sites. Furthermore, all variants were found to reduce binding energy between NAGK and dynein subunit DYNLRB1, as revealed by protein–protein docking and MM-GBSA binding energy calculation supporting their deleteriousness on non-canonical function. We hope these findings will direct future studies to gain more insight into the role of these variants in the loss of NAGK function and their role in neurodevelopmental disorders.An enzyme of the mammalian amino-sugar metabolism pathway,  N-acetylglucosamine kinase  is a major enzyme from the sugar-kinase/Hsp70/actin superfamily, which is involved in the conversion of GlcNAc (N-acetylglucosamine) to GlcNAc-6-phosphate, a catalytic event present in amino sugar metabolism , wh, wh27], To analyze the NAGK conformational stability, the RMSD value of the sub-trajectories was again calculated as an indication of overall protein stability. The RMSD value, as compared to wild-type, was found higher in G120E and A156D than G11R . The RMS2  of all variants was calculated and compared with wild-type. The SASA indicates solvent accessibility, where a decrease in SASA describes the shrunken structure. At the same time, a high value denotes protein flexibility suggesting that the hydrophobic core of the protein appeared to be exposed in the aqueous surrounding due to the loss of hydrophobic interactions among nonpolar residue clusters . As show150 to S275), where the residues in the NAGK small domain were seen to have a high fluctuation only in A156D  and accepting proton during the nucleophilic attack on the γ-phosphate of ATP [To recognize the effect of variants in the local flexibility of the protein, we calculated the root mean square fluctuations (RMSF) value of NAGK in both wild-type and variants, which indicates that amino acid substitution increased residual flexibility. As represented in RMSF analysis , it was in A156D A, all vae of ATP . 36 showed a high fluctuation in the case of A156D and other residues (H37 to I40), along with high fluctuations in G11R and G32R compared to the wild-type (269 to L275), was seen to have more fluctuation in A156D and G11R than the wild-type. In addition, residues in the region L250 to V269 and S275 to S300 showed reduced fluctuations in G120E and G32R. The residual fluctuations in the PHOSPHATE2 motif also deviated more in G120E and A156D; however, residual fluctuations in the hinge region remained unaffected. Additionally, G120E and A156D showed high RMSF values (79 to R85 near the substrate binding site (S76 to D79).Similarly, NF values C,D in th2 to L71 and P67 to I104, while anti-correlated motion occurred between the residues E240 to T303 and F302 to D330. In addition, a positive correlation was found in the region between the region G32 to V46 and A295 to T303, and also between G77 to R94 and A295 to T303. Conversely, a considerable induction of anti-correlated motion was observed between the residues A2 to L71 and E153 to N234, and this region (E153 to G243) was also found to show a negative correlation with the residues of L73 to G110. Furthermore, G11R was also seen to induce anti-correlated motion between I159 to Y205 and L242 to H325. Similar trends in the anti-correlated motion were also found in G32R and A156D, specifically in the region between the residues A2 to L71 and E153 to G243 as well as the correlative motion between the region of residues A2 to L71 and P67 to I104. Unlike G32R and A156D, G120E showed reduced correlative and anti-correlated motions in these regions. Nevertheless, it showed mixed motion between the residues A2 to L71 and I253 to S344. A156D showed an increased anti-correlated motion in the region between the residues V46 to T105 and D118 to D152, and correlative motion between the region T105 to G142 and L267 to I336. The dynamic insight gained from DCCM analysis further supports that variants caused correlative motions in the substrate binding site and in the active site residues, specifically PHOSPHATE and ADENOSINE motif.As RMSF highlighted the variants induced conformational changes in both substrate and ATP binding sites, we incorporated the dynamic cross-correlation map (DCCM) analysis to understand their effects on NAGK correlative motion. Again, to expose the changes in protein dynamics, we conducted principal component analysis (PCA), representing most of the dominant motions during the simulations ,29. RemaTo compare the provable conjoined movements, eigenvectors (EV) of the first three PCs were drawn in a two-dimensional plot, indicating conformational distribution states by color-coded dot representation, described briefly in 145 to D152, where high induction was observed in G120E (76 to D79), but induced mobility in the ADENOSINE binding motif of the ATP binding site . A156D also produced high mobility in all hinge regions as well as in PHOSPHATE2 and adenosine motifs in the ATP binding regions  reduced residual mobility.The residual mobility in NAGK variants, which was highlighted by PC1, is visualized in in G120E C. G11R sing site A,E. On t regions D. Both v148 to S155, where at this region, wild-type showed more bending conformation. Furthermore, G11R introduced more bend conformation in the residues F208 to R212 and decreased A-helix conformation. In the C-terminal region (D330 to S340), G11R produced more bend and coil conformation and reduced A-helix formation during the simulation. A similar trend of the A-helix formation was also revealed in the C-terminal region (D330 to S340) of the G32R variant , G120E reduced 3-helix formation; instead, it introduced turn conformation. A156D reduced A-helix formation in the NAGK large domain  algorithm on wild-type and variant simulation trajectories to analyze the changes in NAGK secondary structure elements . As show variant , and G32ormation . In the e domain , especiaof A156D .59AGVDPLVPLR69 [Our previous report evidenced the physical interaction of NAGK in the dynein complex, where it interacts with DYNLRB1 by its small domain and promotes dynein-mediated functions ,13,14,34In this study, a series of analyses have been incorporated to understand the changes in NAGK structural and conformational dynamics caused by missense variants identified by various bioinformatics tools. Previous studies on NAGK crystal structure suggested that NAGK confers large conformational changes during the catalytic process, like other proteins from kinase/Hsp70/actin superfamily, allowing the small and large domains to be closely connected with substrates. However, this dynamic change is not only critical for substrates selectivity but also for its structural functions, which encouraged us to examine the dynamic nature of NAGK in the presence of deleterious variants.To identify the potential deleterious missense SNPs, we used different bioinformatics tools with various features and parameters to minimize the prediction errors and maximize the reliability and accuracy of the prediction ,35. Thus2+ and coordinates nucleophilic attack of the γ–phosphate group [Accumulating studies in functional genomics evidenced the fundamental roles of evolutionary information in detecting the disease-causing mutations ,37. Thuste group . Thus, tOn the other hand, various analyses from MD simulation, such as RMSD and Rg analysis, revealed the structural changes in NAGK in both wild-type and variant form, concluding that variants induced a substantial increase in structural flexibility. In support of this finding, SASA analysis added that the high flexibility induced by all variants, except G120E, may lead to expanding solvent-exposed area, resulting in protein misfolding and being deemed responsible for loss of function. A decreased SASA value, which was observed for G120E, suggested decreasing total protein solubility, which can also be a negative factor of protein–protein interactions .All of the variants also showed different correlative motions compared to wild-type NAGK. The correlation analyses show a high anti-correlation between the domains induced in the variants, indicating global conformational changes so that the domains of the NAGK are pushed away from each other. Furthermore, the conformational ensembles of wild-type structure in PCA analysis were clustered into two distinct metastable states divided by a substantial energy barrier. These distinct clusters might provide an essential aspect of the control mechanism and suggest that NAGK performs periodic conformational shifting to reorient its terminal domains. As previous study evidenced, substrate-binding in NAGK differs depending on domain movement, from open to close formation, where the closed configuration ensures the tight binding of substrates . Hence, 145 to D152 , polymorphism phenotyping v2 (Polyphen-2), Combined Annotation-Dependent Depletion (CADD), Consensus deleteriousness score of missense mutations (Condel), M-CAP, MutPred, MutationAssessor, protein variation effect analyzer (PROVEAN), predictor of human deleterious single nucleotide polymorphisms (Phd-SNP), I-Mutant3.0, and SNAP2. Here, the prediction method by the SIFT tool is based on the PSI-Blast algorithm [The National Center for Biological Information (NCBI) SNP database (dbSNP) provides detailed information about the single nucleotide variations of any gene sequence, and this database was used for collecting relevant lgorithm , which ilgorithm  for detelgorithm . PolyPhelgorithm ,45. Polylgorithm . In the lgorithm . CADD islgorithm  and can lgorithm . Condel lgorithm ,50. M-Calgorithm . The Mutlgorithm ,53. Predlgorithm , dependilgorithm . PROVEANlgorithm  is a seqlgorithm ,57. The lgorithm  softwarelgorithm . From thlgorithm . I-mutanlgorithm . The DDGlgorithm ,62.NAGK gene, the Consurf web tool was used [NAGK that were found in the highly conserved region for further analyses. A score from 1 to 4 was considered as a variable, whereas scores between 5 and 6, and 7 to 9 were considered as intermediate and conserved, respectively.To perform the conservation analysis of the native was used . This wewas used ,64. The To perform molecular dynamics simulation, the three-dimensional crystal structure of NAGK was first retrieved from the protein data bank (PDB ID: 2CH6) and prepared the following energy minimization procedure with Optimized Potential for Liquid Simulations (version 3e), as described earlier ,65,66,67+ or Cl-) to neutralize the cell. Following the simulated annealing method, the system was energy minimized using the steepest gradient approach (5000 cycles). At physiological conditions of  [MD simulation was performed by YASARA Dynamics software by using Assisted Model Building with Energy Refinement (AMBER 14) force field ,71, as p9% NaCl) , MD simu9% NaCl) . During 9% NaCl) ,81. Each9% NaCl)  and VMD 9% NaCl) ,84,85. T9% NaCl) ,87. In a9% NaCl)  package 9% NaCl) , providi9% NaCl) . The mat9% NaCl) ,16,65,69The first 3 principal components were used to calculate the cosine content, which indicates the statistical significance of convergence of the trajectories, which was accomplished using the essential dynamics program of GROMACS simulation package. Here, a cosine value lower than 0.7 is considered a good convergence, while values close to 1 indicate that the simulation is not converged . To analwild/variant-DYNLRB1 complex, a short MD simulation (0.5 ns) was again performed using the similar approach described earlier. The lowest energy conformer from MD refine was used for binding energy calculation by MM-GBSA method using the following equation:To predict the interacting model of NAGK–DYNLRB1 , protein–protein docking was performed in the SwarmDock server , which pcomG) and unbound-state systems (proteinGrec_ + proteinGlig_) is defined by ∆bindG.∆bindG can be described into three additional terms: ∆EMM represents total gas-phase energy, which is the total of ∆internalE, ∆electrostaticE, and ∆vdwE); ∆solG describes the total energy of polar (∆GBG) and nonpolar (∆SAG) contributions to solvation; and the conformational entropy upon the binding is described by T∆S.Here, the change in total free energy between bound-state  software was used to analyze the MD trajectories statistically. To compare the simulation results, p values of < 0.0001 were considered to be highly significant, which were performed with two-tailed, equal-sample variance Student’s t-tests.In this study, correlation among different bioinformatics tools was predicted by SPSS v19 software . To find out the most significant combinations, In summary, the identified NAGK missense variants, G11R, G32R, G120E, and A156D, are potentially damaging to NAGK structure and function. All of these variants were seen to disrupt the integrity of the catalytic site, induce high correlative motions, and reduce the binding energy of NAGK to DYNLRB1, indicating their damaging effect on NAGK general structural functions. Although further experimental verifications to assess the effect of these variants in NAGK functions is recommended, this study provides a starting point for further investigation of their associations in various brain developmental genetic disorders. The knowledge gained from this study may be directly helpful in efforts toward gene-based therapy and CRISPRs.


The proposed device provides a simple, low-cost, efficient, and robust way to detect optical fiber signals with intriguing capabilities in terms of distributed photodetection and on-line power monitoring, which is highly desirable for a fiber-optic communication system.Graphene has been widely used in photodetectors; however its photoresponsivity is limited due to the intrinsic low absorption of graphene. To enhance the graphene absorption, a waveguide structure with an extended interaction length and plasmonic resonance with light field enhancement are often employed. However, the operation bandwidth is narrowed when this happens. Here, a novel graphene-based all-fiber photodetector (AFPD) was demonstrated with ultrahigh responsivity over a full near-infrared band. The AFPD benefits from the gold-enhanced absorption when an interdigitated Au electrode is fabricated onto a Graphene-PMMA film covered over a side-polished fiber (SFP). Interestingly, the AFPD shows a photoresponsivity of >1 × 10 As an optical to electrical signal converter, the photodetector is an indispensable element in every fiber-optic communication system ,2,3,4. I2 V−1 s−1), graphene-based photodetectors (GPD) can potentially operate at speeds >500 GHz  than TM mode. However, with the Au film, the TM mode couples more efficiently with coated materials, leading to a much larger Im[effn]. This is caused by the light field confinement of the Au film for TM mode  values for the TE and TM modes are different owing to the circular asymmetry of SPF. Thus, the photoresponse of the AFPD is sensitive to the incident polarization, which was verified experimentally  were achieved over a broadband region of 980–1620 nm with a nearly uniform responsivity in telecom C-band. This AFPD is easy to fabrication, low cost, and highly compatible with the current fiber-optical communication system, thus, it facilitates the development of all fiber electrooptical devices.In conclusion, an Au enhanced graphene-based AFPD with broadband ultrasensitivity over the near-infrared region has been demonstrated. The multiple interdigitated Au fingers enhanced the light–graphene interaction, creating a dramatically enhanced local optical field near the graphene. The extended interaction length of the fiber guiding mode and the coated materials resulted in the high photoresponse. The AFPD can detect light with a power that ranges from low to 0.11 nW, with a responsivity as high as 5.7 × 10


Background and objective: Idiopathic pulmonary fibrosis (IPF) is an aggressive fibrotic pulmonary disease with spatially and temporally heterogeneous alveolar lesions. There are no early diagnostic biomarkers, limiting our understanding of IPF pathogenesis.Methods: Lung tissue from surgical lung biopsy of patients with early-stage IPF (n = 7), transplant-stage IPF (n = 2), and healthy controls (n = 6) were subjected to mRNA sequencing and verified by real-time quantitative PCR (RT-qPCR), immunohistochemistry, Western blot, and single-cell RNA sequencing (scRNA-Seq).Results: Three hundred eighty differentially expressed transcripts (DETs) were identified in IPF that were principally involved in extracellular matrix (ECM) remodeling, lipid metabolism, and immune effect. Of these DETs, 21  were selected and verified by RT-qPCR. Differences in DMD, FASN, and MMP7 were also confirmed at a protein level. Analysis of scRNA-Seq was used to trace their cellular origin to determine which lung cells regulated them. The principal cell sources of DMD were ciliated cells, alveolar type I/II epithelial cells (AT cells), club cells, and alveolar macrophages (AMs); MMP7 derives from AT cells, club cells, and AMs, while FASN originates from AT cells, ciliated cells, and AMs.Conclusion: Our data revealed a comprehensive transcriptional mRNA profile of IPF and demonstrated that ECM remodeling, lipid metabolism, and immune effect were collaboratively involved in the early development of IPF. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown cause, characterized by a histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP) with spatial heterogeneity, temporal heterogeneity, and honeycomb lesions . IPF is n = 7) who underwent SLB and those with transplant-stage IPF (n = 2) who underwent lung transplantation and compared the results with tissue obtained from healthy controls. Of the 380 differentially expressed transcripts (DETs), 21 target DETs that were mainly related to ECM remodeling, immune effect, and lung lipid metabolism-related pathways were selected for further verification by real-time quantitative PCR (RT-qPCR) and single-cell RNA sequencing (scRNA-Seq) analysis. Our findings highlighted the central and coordinating roles of different cells, pathways, and genes in the development of IPF.In the present study, we hypothesized that mRNA-Seq analysis of IPF lung tissue obtained from surgical lung biopsy (SLB) and lung transplantation would provide more comprehensive biological information and facilitate early diagnosis and a better understanding of the comprehensive pathogenesis of heterogeneous IPF. We performed mRNA-Seq on lung tissue from a cohort of patients with early-stage IPF  treated at the ILD Center of the First Affiliated Hospital of Guangzhou Medical University between 2014 and 2018. The study protocol was approved by the local independent ethics committee (2020-71). Informed consent was obtained from participants.Total RNAs of tissue were extracted using a Trizol reagent kit, and sequencing and analysis performed using the Illumina novaseq 6000 platform and Bowtie2, HISAT2 (v2.1.0), StringTie (v1.3.1), and R package gmodels, respectively. Patient inclusion and exclusion criteria, methods of mRNA expression analysis, 21 target gene selection and RT-qPCR, protein expression, and cell sources of DMD, MMP7, and FASN are detailed in the in vitro were repeated at least three times with three samples. Statistical significance was set at p < 0.05.Total transcript expression data were analyzed using Fisher's exact test or Wald test at a false discovery rate (FDR) of 5% and |log2FC| > 1. Statistical analysis for RT-qPCR and Western blot (WB) was performed with a two-tailed Student's t-test using GraphPad Prism software (v 8.0.2.263), or SPSS (v25.0). Results are shown as mean ± SD in the table or mean ± SEM in figures. All expression experiments conducted Ten patients with suspected IPF and six healthy controls were initially recruited to the study. IPF was confirmed in nine out of the ten patients . Compared to healthy lung tissue sections , patientThe mRNA-Seq experiments were performed using nine IPF and six HC lung tissue samples, and 101,590 transcripts were identified. Principal component analysis of all transcripts revealed that the transcriptional mRNAs of IPF tissue differed to those of the HC samples . A totalFollowing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for downregulated and upregulated DETs, significant BP  terms of GO and KEGG pathways were identified and are shown in Target genes were selected based on the criteria of |log2FC| > 2 and genes expressed in at least two-thirds of IPF or HC samples. In total, 21 target genes were selected and classified into the following groups: 1) DMD, MMP7, POSTN, ECM2, and MMP13 related to ECM remodeling, 2) FASN, FADS1, SDR16C5, ACAT2, ACSL1, CYP1A1, and UGT1A6 associated with lipid metabolism, and 3) CXCL13, CXCL5, CXCL14, IL5RA, TNFRSF19, CSF3R, S100A9, S100A8, and S100A12 allied with immune effect. Following mRNA-Seq analysis, we determined that each of the 21 target genes may have multiple DETs: two transcripts in DMD, two in ECM, four in CYP1A1, three in SDR16C5, two in FASN, and three in CSF3R . In addiTo further verify the regulated genes, WB analysis was performed using IPF and HC tissue for DMD , MMP7 and FASN . The immunohistology chemistry (IHC) results in IPF is usually characterized by a histopathologic and/or radiologic pattern of UIP with spatial heterogeneity, temporal heterogeneity, and the presence of honeycomb lesions . InvestiSeveral genes such as MMP7, CSF3R, and S100A12 identified and characterized in our study have previously been reported . For insDespite the confirmation of inflammatory cytokines and innate and adaptive immune cell infiltration in IPF, several clinical experiments of immunosuppressive therapy for IPF have failed. This has downplayed the role of chronic inflammation and immune effect in the pathogenesis of IPF . NonetheDMD is a novel gene closely related to ECM remodeling in IPF. We found that DMD was mainly expressed by ciliated cells and secondarily expressed in AT and club cells in the lung tissue. Interestingly, there was an about 1.5-fold upregulation of DMD in AT and club cells of IPF tissue, while there was no significant difference between the ciliated cells of IPF and HC groups, suggesting that the role of DMD in IPF development may be cell type-dependent. It is worthy of note that the DMD gene is one of the largest protein-coding genes in the human genome, existing on the X chromosome, and encodes and synthesizes 427 KDa dystrophin protein that is distributed principally in the myocardium, smooth muscle, and skeletal muscle . EdematoThe results of our study, from changes in the overall molecular level of IPF to alterations in the lung cells, showed that ECM remodeling, lipid metabolism, and immune effect are complex during the early development of IPF, suggesting that no single cell, gene, or pathway can contribute to the complex and heterogeneous nature of the disease. In addition, our findings supplement and reinforce the present transcriptome profile of human IPF disease.


From the results, the proposed humidity sensor array opens a new gateway for a wide range of humidity sensing applications with a linear function.This paper proposes a signal processed systematic 3 × 3 humidity sensor array with all range and highly linear humidity response based on different particles size composite inks and different interspaces of interdigital electrodes (IDEs). The fabricated sensors are patterned through a commercial inkjet printer and the composite of Methylene Blue and Graphene with three different particle sizes of bulk Graphene Flakes (BGF), Graphene Flakes (GF), and Graphene Quantum Dots (GQD), which are employed as an active layer using spin coating technique on three types of IDEs with different interspaces of 300, 200, and 100 µm. All range linear function (0–100% RH) is achieved by applying the linear combination method of nine sensors in the signal processing field, where weights for linear combination are required, which are estimated by the least square solution. The humidity sensing array shows a fast response time (T The humidity sensor can measure and detect different parameters such as impedance, resistance, and capacitance3. For humidity sensing, many researchers are working to improve the following parameters like hysteresis, temperature dependence, linearity, sensitivity, reproducibility, time response, and low production cost3. It is impossible to fabricate a humidity sensor, that can deliver all the above mentioned parameters. In these expectations, for the commercialization of humidity sensors, several researchers are working on different designs based on interdigital electrodes (IDEs)4, capacitance-based design5, piezoelectric6, and surface acoustic waves7. In all of these proposed humidity designs, the IDEs based humidity sensors are more preferred for environment monitoring as it provides higher sensitivity by efficiently detecting any change in active film characteristics on all electrode fingers3. IDEs are easy to fabricate and a single sensing layer is required for environment monitoring8. In humidity sensor, RH presents the percent ratio of actual vapor density and saturation vapor density, and when air is fully saturated with water vapor and cannot able to hold any more water vapor, this environment condition is called fully saturated with 100% RH3.Relative humidity (RH) is an important parameter to be under observations in the environment for different applications like industry, food, health, and even space applications9, metal oxide10, biomaterials1, organic materials11, inorganic materials2, organic–inorganic materials12, and other nanocomposites materials3 with desired properties that can exhibit the target performance parameters when employed as active elements for humidity sensing. This approach helps to achieve a few targets, but at the same time ignores a few parameters like user range of detection, friendly interface, response time, etc.4. Other researchers are mainly focusing on working mechanism, humidity sensor design, humidity sensor configuration , while they are paying less attention to material aspect13. Whereas, few researchers are applying a new type of composite like Graphene/(Zinc oxide)2, which is impedance based humidity sensor in parallel configuration. Here, it is showing a good response at middle range of humidity level, but it is not sensitive for a low range of humidity, due to very high impedance at a low range of humidity. In order to increase the sensitivity of the impedance based humidity sensor, generally insulator material Polyvinyl phenol (PVP) is mixed with conductive material Poly-poly(styrenesulfonate) (PEDOT:PSS)14, in which impedance of PVP decreased by mixing PEDOT:PSS. However, the sensitivity of the humidity sensor is still not sufficient for the full range. To improve the sensitivity of the humidity sensor at a low range, two interdigital electrodes are used in series13, in which one humidity sensor is coated with PEDOT:PSS and the other coated with MoS2 with RH percent (%) range from 0 to 80% with almost linear response. However, the sensor needs several improvements for a full range of humidity detection from 0 to 100% RH with linear response.So far, many researchers are studying different materials to detect RH like 2D materials3. Graphene is widely used in various sensor applications, and it is very sensitive to immediate environment change, due to the presence of pi-bond17. However, Graphene is not sufficiently sensitive to  a wide range of RH, because of its high conductivity3. To improve this problem, MB and Graphene nanocomposites are applied, which increases the sensitivity and sensing range as shown in Fig. 18. The MB and Graphene composite with different particle sizes is utilized in the ratio of 1:1 as following MB and bulk Graphene flakes composite (MB/BGF), MB and Graphene flakes composite (MB/GF), MB and Graphene quantum dots composite (MB/GQD). To design all range systematic humidity sensing array, inkjet printing, and spin coating technique is utilized. The fabricated 3 × 3 sensing array is tested with a homemade humidity sensing setup. The overall combined impedance response of IDEs physical connection in parallel of all columns and rows provides a wide piecewise linear, and a perfect linear function can be obtained,  and further all array IDEs are processed using the linear combination method in the signal processing field to achieve all range linear response. The proposed sensing array shows fast response time (Tres) and recovery time (Trec). These results proposes the design and fabrication method of a novel humidity array sensor with linear characteristics on all sensing range.To cover the chemical and physical aspect of all ranges of RH detection, composite inks of Methylene Blue (MB) with three different particle sizes of Graphene are utilized, and different interspaces of three types of IDEs. In this paper, a 3 × 3 sensing array is demonstrated as shown in Fig. The material for humidity sensing is one of the main parameters to analyze the change in impedance with the change in water vapors blown on it and this change is easily detected with fingers of IDEs. Three inks for the active layer were prepared as follows; composite of MB/BGF, MB/GF, and MB/GQD was synthesized as shown in Supplementary Fig. In IDEs on the proposed sensor array, they contain many electrode figures, which improves the sensitivity. IDEs are more sensitive as compared to two electrodes because all figures electrodes are in parallel to sense the change in the electric property of the active layer. To fabricate the 3 × 3 humidity sensing array on PET substrate, the IDEs were designed using EAGLE version 9 in Dxf format with the same electrode spacing in each row and different electrode spacing in each column like 300, 200, and 100 μm. The 3 × 3 IDEs sensing array design file is converted to a BMP file and Dimatix Drop Manager converts the BMP file into an open file format. The ptn file was uploaded to the inkjet printing system. The 1 pL 16 nozzles cartridge was filled with 3 ml of Ag ink. The 25 V was applied on cartridge nozzles for stable printing. The temperature of the printing platform was set at 40 °C as shown in Supplementary Fig. The nanocomposites of MB/BGF, MB/GF, and MB/GQD are used to fabricate the active layer on the top silver patterned IDEs by using spin coating technology as shown in Supplementary Fig. The surface morphology of Ag, MB, BGF, GF, and GQD were characterized with TESCAN MIRA 3 scanning transmission electron microscope (STEM). The element composition of Ag, MB, and BGF, GF, and GQD were analyzed with energy-dispersive X-ray spectroscopy (EDS). The 2D and 3D nano-profile of IDEs and composite films of MB/BGF, MB/GF, and MB/GQD were analyzed with NV-2000 Universal non-contact surface profiler. The structural and chemical investigation of MB and Graphene were characterized by using a Lab Ram HR Evolution Raman spectrometer . The impedance response of the sensing array towards change in relative humidity was recorded in a homemade environmental controlled chamber.– ions at the low level of humidity, and acts as an electron donor. During continuous absorption of water molecules, the physio absorbing layer is formed on the chemisorbed water molecule layer as shown in Fig. The schematic of the active layer mechanism based on IDEs is explained in Fig. − ions at the high level of humidity as given reaction given in Eq. , which become the main hurdle to achieve linear response for a longer time. This work provides a solution to solve sensor variation problems using linear combination techniques based on signal processing to achieve a linear response. The wider piecewise linear function in a range of 0–100% RH can be obtained by the sensor elements combination in rows and columns with fast response and recovery time 0.2 s and 0.4 s, respectively. This approach opens a gateway to design humidity sensors for the different operating conditions using the same material by adopting different combinations in sensing array with a signal processing technique.In Table As the concluding remarks, we presented all range inkjet printed linear and wide range humidity sensing 3 × 3 array with different interspaces of IDEs. The three different composite inks MB/BGF, MB/GF, and MB/GQD with different particle sizes were used for 3 × 3 array processed sensing. The impedance response of each sensor in the sensor array was analyzed at 1 kHz. The highly linear and wide-range response is achieved in a range of 0–100% RH with linear combination by using the signal processed technique. Every column and row with different electrode spacing or particle sizes, respectively, were physically connected in parallel, and the sensor arrays with the wide piecewise linear were demonstrated. The proposed sensor array shows fast response time and recovery time ~ 0.28 and 0.48, respectively. The proposed sensor array opens a new gateway for environment sensing systems, which can provide the related information with design parameters for all range linearity.Supplementary Information.


Cymodocea nodosa invaded by Caulerpa cylindracea and in a monospecific settlement of C. cylindracea at monthly intervals. For comparison the ambient prokaryotic picoplankton community was also characterized. At the OTU level, the microbial community composition differed between the ambient water and the epiphytic communities exhibiting host-specificity. Also, successional changes were observed connected to the macrophyte growth cycle. Taxonomic analysis, however, showed similar high rank taxa (phyla and classes) in the ambient water and the epiphytic communities, with the exception of Desulfobacterota, which were only found on C. cylindracea. Cyanobacteria showed seasonal changes while other high rank taxa were present throughout the year. In months of high Cyanobacteria presence the majority of cyanobacterial sequences were classified as Pleurocapsa. Phylogenetic groups present throughout the year  constituted most of the sequences, while less abundant taxa showed seasonal patterns connected to the macrophyte growth cycle. Taken together, epiphytic microbial communities of the seagrass C. nodosa and the macroalga C. cylindracea appear to be host-specific and contain taxa that undergo successional changes.Surfaces of marine macrophytes are inhabited by diverse microbial communities. Most studies focusing on epiphytic communities of macrophytes did not take into account temporal changes or applied low sampling frequency approaches. The seasonal dynamics of epiphytic microbial communities was determined in a meadow of  Marine macrophytes  are important ecosystem engineers forming close associations with microorganisms belonging to all three domains of life  microbial taxa, such as Caulerpa are also closely associated with their microbial communities  the assessment of differences in the bacterial and archeal communities between host species and settlements of C. cylindracea and (ii) the evaluation of differences between surface associated and free living (ambient seawater) communities. In addition, these differences were evaluated on a monthly scale providing insight into seasonal changes (iii).Since marine macrophytes in temperate zones are exhibiting seasonal changes in growth and physiology , while C. cylindracea thalli were sampled in the same invaded meadow  and in a monospecific settlement  of C. cylindracea located in the proximity (20–50 m) of the invaded meadow at approximately monthly intervals from November 2017 to October 2018  to remove loosely attached microbial cells. Ambient seawater was collected in 10 L containers by diving and transported to the laboratory where 10–20 L were filtered through a 20 μm net. The filtrate was further sequentially filtered through 3 and 0.2 μm polycarbonate membrane filters  using a peristaltic pump. Filters were briefly dried at room temperature and stored at -80°C. Seawater samples were also collected approximately monthly from July 2017 to October 2018.Sampling was performed in the Bay of Funtana, northern Adriatic Sea . The sea floor in the bay is partly covered by the invasive macroalga . nodosa . C. nodober 2018 . Leaves C. nodosa and C. cylindracea was isolated from a pool of leaves (1 g wet weight) or thalli (2 g wet weight) on the sampling day using a previously modified and adapted protocol that allows for a selective epiphytic DNA isolation  was added. DNA was precipitated by adding 1 volume of chilled isopropanol, incubating the mixtures overnight at -20°C and centrifuging at 20,000 × g and 4°C for 20 min. The pellet was washed twice with 500 μl of chilled 70% ethanol and centrifuged after each washing step at 20,000 × and 4°C for 5 min. Dried pellets were re-suspended in 50–100 μl of deionized water. One DNA sample originating from seawater picoplankton was obtained per each sampling point.DNA from surfaces of https://earthmicrobiome.org/protocols-and-standards/16s/) were used .Illumina MiSeq sequencing of the V4 region of the 16S rRNA gene was performed as described previously . For alignment and classification of sequences the SILVA SSU Ref NR 99 database  was used  using mothur  were expressed as the Jaccard's (on presence/absence data) and Bray-Curtis similarity coefficient, respectively. The coefficients were calculated on the OTU data table using vegan's function vegdist and converted from dissimilarities to similarities  followed by a pairwise comparison using the Mann-Whitney U-test (function pairwise.wilcox). Bonferroni correction was used to address the problem of multiple comparisons.Pipeline data processing and visualization was done using R (version 3.6.0) .A total of 1.7 million sequences after quality curation and exclusion of sequences without known relatives (no relative sequences) and eukaryotic, chloroplast, and mitochondrial sequences were obtained . The numr sample . Based or sample . In addiC. nodosa and the macroalga C. cylindracea were analyzed. In addition, 18 samples (one of the samples was sequenced twice) originating from the ambient seawater were also processed for comparison. Generally, richness estimators and diversity indices showed similar trends. On average, higher values were found for C. cylindracea  than for C. nodosa  and lowest values were obtained for the microbial community of the ambient seawater   communities were characterized by slightly higher values in spring and summer than in autumn and winter  , 3. Tempd winter .R = 0.96, p < 0.001). The highest proportion of shared OTUs and community was found between mixed and monospecific C. cylindracea , while lower shared values were calculated between ambient seawater and epiphytic communities . Shared proportions of OTUs and communities between C. nodosa and C. cylindracea (either mixed or monospecific) were approximately in-between the values obtained for the comparison of ambient seawater with all other communities and for the comparison of the mixed and monospecific C. cylindracea associated community. Seasonal changes of C. nodosa associated communities indicated a separation between spring, summer, and autumn/winter samples . For C. cylindracea associated communities a separation between summer and autumn/winter/spring samples was observed that was, however, not as strong as for C. nodosa associated communities  and C. cylindracea (mixed [26.3 ± 2.1%] and monospecific [27.2 ± 2.0%]) associated communities (p < 0.0001), while mean proportions of shared communities between consecutive sampling points did not show such a difference , although in ambient seawater higher fluctuations could be observed  over archeal sequences  and C. cylindracea mixed (7.7 ± 3.9%) and monospecific (7.8 ± 2.4%) associated communities in autumn (p < 0.0001) and for ambient seawater communities in winter (8.8 ± 7.5%). Large taxonomic differences between surface associated and ambient seawater cyanobacterial communities were observed. Ambient seawater communities were mainly comprised of Cyanobium and Synechococcus, while surface associated communities were comprised of Pleurocapsa and sequences within the class Cyanobacteriia that could not be further classified  in spring and summer , uncultured Saprospiraceae, sequences without known relatives within the Flavobacteriaceae (no relative Flavobacteriaceae) and uncultured Rhodothermaceae were found. Some groups showed minor seasonal changes such as no relative Flavobacteriaceae whose sequences were more abundant from November 2017 until June 2018. In contrast, uncultured Rhodothermaceae showed higher proportions from June 2018 until the end of the study period. Surface associated Bacteroidota communities were very diverse as observed in the high proportion of taxa clustering as other Bacteroidota , HIMB11 and the OCS116 clade, while surface associated communities were composed mainly of no relative Rhodobacteraceae and to a lesser degree of Pseudoahrensia, Amylibacter, and sequences without known relatives within the Alphaproteobacteria (no relative Alphaproteobacteria) and Hyphomonadaceae (no relative Hyphomonadaceae). Representatives of no relative Rhodobacteraceae comprised on average 54.7 ± 11.5% of all alphaproteobacterial sequences in the epiphytic community  and Granulosicoccus. Beside these two groups specific to all three epiphytic communities, C. nodosa was characterized by Arenicella, Methylotenera, and sequences without known relatives within the Burkholderiales , while Thioploca, Reinekea, and sequences without known relatives within Cellvibrionaceae (no relative Cellvibrionaceae) were more specific to both mixed and monospecific C. cylindracea. In addition, Arenicella was more pronounced in November and December 2017, while no relative Burkholderiales and Methylotenera were characteristic for the period from March until May 2018. For the C. cylindracea specific taxa no relative Cellvibrionaceae and Reinekea showed seasonality and were characteristic for samples originating from June to October 2018. In addition, similar to Bacteroidota, a large proportion of the surface associated community was grouped as other Gammaproteobacteria indicating high diversity within this group , Desulfobulbaceae (no relative Desulfobulbaceae), and Desulfocapsaceae  followed by C. nodosa and lowest richness was found in ambient seawater microbial communities. Higher richness of microbial communities associated with macrophytes than in ambient seawater has been described earlier  were identified to be persistent. It has been suggested that members of this family are important in the hydrolysis and utilization of complex organic sources , a plant hormone . ZZ and GH were supported by the Austrian Science Fund (FWF) project ARTEMIS (project number P28781-B21).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Transparent conductive electrodes based on graphene have been previously proposed as an attractive candidate for optoelectronic devices. While graphene alone lacks the antireflectance properties needed in many applications, it can still be coupled with traditional transparent conductive oxides, further enhancing their electrical performance. In this work, the effect of combining indium tin oxide with between one and three graphene monolayers as the top electrode in silicon heterojunction solar cells is analyzed. Prior to the metal grid deposition, the electrical conductance of the hybrid electrodes was evaluated through reflection-mode terahertz time-domain spectroscopy. The obtained conductance maps showed a clear electrical improvement with each additional graphene sheet. In the electrical characterization of the finished solar cells, this translated to a meaningful reduction in the series resistance and an increase in the devices’ fill factor. On the other hand, each additional sheet absorbs part of the incoming radiation, causing the short circuit current to simultaneously decrease. Consequently, additional graphene monolayers past the first one did not further enhance the efficiency of the reference cells. Ultimately, the increase obtained in the fill factor endorses graphene-based hybrid electrodes as a potential concept for improving solar cells’ efficiency in future novel designs. Voc) in excess of 740 mV. In addition, by employing amorphous silicon in extremely thin layers the parasitic absorption can be minimized and high short-circuit currents (Jsc) can be obtained. However, the lateral electrical conductivity in these layers is insufficient for providing good carrier transport towards the metal-grid fingers, so a transparent conductive oxide (TCO) is needed. Typically, indium tin oxide (ITO) is the TCO of choice for SHJ technology with aluminum-doped zinc oxide also being widely studied as a potential substitute of ITO due to the scarcity of indium [Silicon heterojunction (SHJ) solar-cell technology is securing a space in the large-volume manufacturing PV market, currently dominated by BSF cells, PERC and PERT cells, thanks to its impressive efficiency and relatively simple structure . Essentif indium . Since tf indium .High transparency and high electrical conductivity are two characteristics typically associated with nanoscale materials, such as carbon nanotubes, graphene, metal nanowires and metal nanogrids. Hence, transparent conductive electrodes (TCE) based on nanomaterials have been integrated into a wide variety of electro-optical applications  with promising results . HoweverFF when compared with the reference cell with only ITO. On the other hand, by increasing the number of GML, the transmittance of the hybrid electrodes decreased accordingly and Jsc was negatively affected. However, by limiting the number of GML to only one, the gains in FF outmatched the losses in Jsc and the efficiency of the devices improved with respect the reference cell. These results highlight the potential for the development of advanced transparent or semitransparent electrodes based on graphene and its application to optoelectronic devices.The optical and electrical properties of hybrid electrodes based on ITO and GML can be modified through the number of GML used. In this work, hybrid electrodes with up to three GML are tested. The hybrid electrodes are fabricated directly in SHJ structures before metal grid deposition. Therefore, the results obtained from the characterization of the hybrid electrodes and the properties of the finished solar cells are closely related. The quality of the graphene layers was established through Raman measurements, whereas the AR properties of the hybrid electrodes was evaluated through reflectance spectroscopy. Contactless measurements of the electrodes sheet resistance were evaluated through THz time domain spectroscopy, illustrating how the hybrid electrodes exhibit a lower sheet resistance with an increased number of GML. Thanks to the lower sheet resistance, the finished solar cells with hybrid electrodes showed improvements in the series resistance and The goal of this research is to evaluate the effect of combining multiple layers of graphene with ITO as the front transparent conductive electrode in SHJ solar cells. For that purpose, very high-quality graphene films were used. In particular, we employed CVD grown graphene purchased from Graphenea S.A., a company specialized in the manufacturing and application of graphene , using an Ar atmosphere and powered by DC . At this point, the graphene monolayers were transferred onto the ITO surface. For the current research, we chose to test the effect of adding between one and three monolayers. Finally, after graphene deposition, Ti and Ag metal contacts were evaporated on the front (through a grid) and on the back (full area) and the cells were annealed for 5 min at 200 °C in a hot plate to recover the passivation lost during the ITO sputtering process [SHJ solar cells were fabricated using a 280 µm-thick flat n-type float zone c-Si <100> with a resistivity of 1–5 Ω·cm. After RCA cleaning, the wafers were stripped of the native oxide by dipping the substrates for 1 min in a 2% HF solution. The wafers were then loaded into a two-chamber PECVD reactor (Elettrorava s.p.a.) where ~5 nm-thick intrinsic a-Si:H layers were deposited on both sides to ensure a good surface passivation. The back side of the wafer was then covered with a ~20 nm n-type a-Si:H film to form the back surface field and electron-selective contact, whereas the front hole-selective contact was realized with the deposition of a ~10 nm p-type a-Si:H layer. Following this, an 80 nm-thick ITO layer was sputtered on the front side through 3.5 cm2O3:SnO2 0/10 wt.%The graphene films were characterized as already in place in unfinished solar cells prior to metallization. Raman microscopy using a 514 nm Ar laser (inVia Renishaw) was used to check the quality of the films and to corroborate the number of graphene films transferred . The eff2 using a class-A solar simulator (Steuernagel SC575) and external quantum efficiency (EQE). Additionally, Suns-Voc measurements were performed using the Sinton Instrument WCT-120 with the appropriate accessory stage to evaluate the series resistance (Rs) [Finished solar cells were characterized by measuring illuminated current–voltage characteristics at AM1.5G conditions and 100 mW/cmnce (Rs) .In the following subsections, the quality of the graphene films as well as their effect on the TCE optical and electrical performance is presented. Lastly, the results of studies on solar cells where the top ITO has been replaced with the hybrid TCEs are also shown.−1, ~2450 cm−1 and ~2690 cm−1, respectively. In Raman spectra of multilayered graphene stacks, the intensity ratio IG’/IG is dependent on the number of graphene layers [IG’/IG > 2 for monolayers, 1 < IG’/IG < 2 for bi-layers and IG’/IG < 1 for tri-layers and beyond. From the spectra shown in IG’/IG intensity ratio would not agree with the number of layers transferred [Raman spectra of the graphene films already transferred onto the ITO in the solar cells were used to evaluate the quality of the graphene films and transferring process. Three different spectra taken at random points in the cells with one, two and three graphene layers are displayed in e layers ,15,16. E−1 and 1620 cm−1, corresponding to the D and D’ bands. The presence of the D and D’ bands require the existence of sp3-C defects for their activation. In the spectra shown, the contribution of both peaks is very small and the defects are possibly rather localized, since not all of the spectra taken displayed these peaks. Nevertheless, some degree of imperfection seems to be present in the transferred layers though it is likely not high enough as to have a negative effect in the proposed application.In addition to the G, G’ and G* bands, a rather weak signal is also detected around 1350 cmThe addition of graphene monolayers onto the ITO surface modifies the optical characteristics of the transparent conductive electrode. The most straightforward effect is the loss in optical transmittance, which has been found to be about 3% on average with each additional graphene sheet in the wavelength of interest for SHJ solar cells . In the n) of the films involved. The thickness (d) of the ITO films are chosen so that the minimum reflectance occurs at a wavelength λ0 ≈ 600 nm according to the condition n·d = λ0/4 [n ≈ 2.5 [n ≈ 2), λ0 has to shift towards higher wavelengths since the thickness remains practically unchanged. In the case of three graphene monolayers, the reflectance spectra measured deviate from the trend created with one and two monolayers and the minimum shifts again towards lower wavelengths.The spectra obtained are typical for an AR coating deposited on a polished silicon wafer. As can be seen, the presence of ITO is able to greatly reduce the reflectivity of the Si polished wafer  can be calculated in the wavelength range of interest according to:Besides the shift in the position of the minimum, it is also relevant to assess the AR properties of the TCEs. To do so, the average reflectance weighted by the AM1.5G spectrum . Within that range, the differences in Rw for the four structures studied are very small. If the range is narrowed even further to 600–1050 nm, the contribution to Jsc represents around 80% of the total and, within that range, the hybrid TCEs show up to a 2.8% lower Rw. For clarity, Rw within those particular wavelengths.From The main point of interest in introducing graphene into the solar-cell structure is to improve the electrical properties of the transparent conductive electrode . In order to characterize the sheet resistance in situ, a contactless technique such as THz-TDS is highly convenient. RSh_ITO and RSh_Gr are the sheet resistance of ITO and graphene, and m is the number of graphene layers. The values obtained using THz-TDS and the range of expected values considering RSh_ITO = 60.2 Ω/sq and RSh_Gr = 450 ± 50 Ω/sq are plotted in When translated to sheet resistance, the conductance maps yield average values that decrease from 60.2 Ω/sq for the cell with bare ITO, to 54.9 Ω/sq, 47.2 Ω/sq, and 37.7 Ω/sq for the cells with one, two, and three graphene monolayers, respectively. Previous results obtained using transmission line measurements  revealedRs, and an improved FF. On the other hand, the overall decrease in transmittance was compensated for by the better AR properties in a large part of the spectrum usable by the solar cells, and Jsc was hardly affected. Together, the net effect was an improvement in the solar-cell efficiency (η). On the basis of these results, for this work we focused on evaluating the effect of going beyond one graphene monolayer. In Jsc, FF, Rs and the overall efficiency η of the cells with hybrid TCEs, with respect to the reference cell with only ITO are presented.In reference , we repoVoc, the soft techniques used for transferring the sheets (thus not damaging the underlying layers) and the fact that the sheets are far from the junction means that values should not be altered. Indeed, we found the Voc measured in the cell with only ITO (708 mV) remained practically unchanged in the cells with a hybrid TCE (707 mV), and thus are not shown in Jsc on the other hand saw a strong decrease when more than one graphene monolayer was used, as seen in Jsc is lost. However, with the addition of a second and third monolayer the loss in transmittance clearly dominates the optical response and the loss in Jsc worsens to 5.5% and 10.5%, respectively.Regarding FF and Rs. As shown, the improvements in these cases are noticeable. As the top contact ITO was replaced with a hybrid TCO with one, two or three graphene monolayers, the value of Rs decreased from 2.46 Ω·cm2 down to 2.10 Ω·cm2, 1.83 Ω·cm2 and 1.65 Ω·cm2, respectively; likewise, the FF increased from 70.7% to 72.6%, 73.5% and 74.6% accordingly. The observed trend is in line with the improvements in sheet resistance of the TCEs obtained with each additional graphene monolayer shown in Voc remained practically unchanged, the effect of the added graphene monolayers on the efficiency is the result of the compromise between the improved electrical characteristics and the worsening of the optical transparency of the TCE. As a result, the device with a single graphene monolayer displayed a 1.6% higher efficiency compared to the reference cell, but the cells with two and three monolayers suffered an efficiency drop of 1.85% and 5.7%, respectively.Lastly, the effect on the overall efficiency is summarized in Rs and FF. The loss in transmission caused with each graphene monolayer means that they need to be kept at a minimum, otherwise the drop in Jsc can be significant. However, in addition to what we have shown there is still clear room for improvement. Among other things, the electrical conductivity of graphene can be increased via chemical doping without sacrificing its transparency [To conclude, in sparency ; and theThis work presents a study on hybrid transparent conductive electrodes based on ITO and graphene and its application as front contacts in silicon heterojunction solar cells. The electrodes consisted of up to three monolayers of CVD-synthesized graphene transferred onto the top of ITO in silicon heterojunction solar cells.The obtained Raman spectra indicated the presence of good quality graphene in stacks of one, two and three monolayers. The effect of the graphene layers on the reflectance spectra depended on the wavelength range considered. In the range between 430–1050 nm (which corresponds to around 95% of the generated photocurrent) a small increase in the weighted reflectance not larger than 1.5% was observed. In the range between 600–1050 nm (which corresponds to around 80% of the generated photocurrent) all of the cells with graphene on top showed better antireflectance properties than the reference cell. The electrical characterization through THz time domain spectroscopy illustrated good electrical contact between the ITO and the stacks of graphene monolayers. For all cases, the sheet resistance of the ITO layer was reduced accordingly to an intimate parallel combination of all the layers.FF thanks to the improved sheet resistance and workfunction matching between the transparent electrode and the metal grid, while the cells’ Voc was hardly affected. On the other hand, Jsc decreased with each graphene monolayer due to a lower optical transmission of the electrode. This effect was mostly cancelled out for one graphene monolayer by the improvement in reflectance in a large part of the usable light, and only 1% of scJ was lost. Overall, the cell with a single graphene monolayer displayed a 1.6% higher efficiency compared to the reference cell, while the cells with two and three monolayers could not improve upon that.The current–voltage characteristics of the solar cells with graphene showed a better series resistance and These results show that graphene can be used to improve the conductance of ITO and that its application can be helpful in increasing the efficiency of solar cells. Furthermore, new strategies to improve the chemical doping of graphene monolayers without sacrificing its transparency are being studied worldwide. The application of such strategies to hybrid electrodes based on graphene, or even to electrodes based on multilayered graphene alone, opens up the possibility of fabricating high-performance electrodes suitable for use in next-generation solar cells and upcoming technologies.


This paper evaluates the potential usage of graphene/crosslinked polyethylene (graphene/XLPE) as the insulating material for high voltage direct current (HVDC) cables. Thermal, mechanical and electrical properties of blends with/without graphene were evaluated by differential scanning calorimetry (DSC), tensile strength, DC conductivity, space charge measurements and water tree aging test. The results indicate that 0.007–0.008% weight amount of graphene can improve the mechanical and electrical insulation properties of XLPE blends, namely higher tensile/yield strength, improved space charge distribution, and shorter/fewer water tree branches. The improvements mainly attribute to the high stiffness of graphene, deep traps introduced by the interaction zones of graphene and XLPE, and the blockage effect of graphene within XLPE. For thermal performance of XLPE blends, graphene nano-fillers have but limited improvement. The crystallinity of the blends barely changes with the addition of graphene. However, the crosslinking degree increases as the additive-like amounts of graphene doped. The above findings provide a guide for tailoring lightweight XLPE materials with excellent mechanical and electrical performances by doping them with a small amount of graphene. As one of the most important part of HVDC, cables directly determine the safety of the system. For cables in alternating current (AC) transmission system, crosslinked polyethylene (XLPE) has been widely used as their insulating material due to its high breakdown strength, low dielectric loss, good mechanical properties and improved thermal resistance6. However, the application of XLPE in high voltage direct current (HVDC) cables still faces multiple problems, the most serious of which is the space charge accumulation and its corresponding consequences, namely electric field distortion, partial discharge, or even breakdown9. To improve the safety and stability of cables in HVDC transmission, it is necessary to modify XLPE materials so as to suppress the accumulation of space charges. Moreover, a quantum leap is also needed for the next generation polymeric HVDC cables with a further increased transmission voltage up to 800 kV10.High voltage direct current  transmission possesses a good number of advantages such as long transmission distance, high transmission efficiency and low active power loss. Along with the mass construction of the power grid, the size as well as the voltage grade of HVDC transmission increases synchronously11. 1–100 nm nanoparticles are uniformly dispersed into the polymer, through which both the physical and chemical properties of the polymer are modified, mostly improved13. The doped polymer, if used as dielectrics, is hence called nano-dielectrics. Lewis first studied nano-dielectrics in 199414. Since then the concept began to gain more research attention. e.g., Smith studied the effect of metal oxide nanoparticle fillers on the electrical properties of XLPE samples and presented the hypothesis, that the nanoparticles will buildup homo-charge at the electrodes, which increases the voltage required for space charge injection due to blocking by the homo-charge15. Wang studied the effect of nano-TiO2 on DC XLPE cables, and found that adding a small amount of nano-TiO2 to XLPE can improve the dielectric properties of polymers, including the crystallinity, conductivity activation energy and DC breakdown strength16. Nevertheless, it is also pointed out that inorganic nanoparticles may cause particle agglomeration and thus being unable to guarantee improvements to the overall electrical properties of the nano-dielectrics17. Furthermore, high loading of inorganic nanoparticle will also make the dielectric heavier, which restrict its industrial application18. Dielectrics with less nanoparticle load and better electrical performance is therefore highly desired.Up to now the most practical strategy to improve the space charge resistance of XLPE is by nano doping24. Recent studies on graphene also indicated it being a promising nanoparticle filler to improve the electrical and thermal properties of dielectrics, though its effect on the mechanical properties has not been investigated yet26.Graphene, with its typical close packed two-dimensional structure and unique properties, has been used in various areas, including transistor, hydrogen storage and photovoltaics technologiesIn this paper, graphene/XLPE nano-dielectric samples with graphene contents of 0%, 0.002%, 0.004%, 0.006%, 0.008%, 0.01% were prepared by solution blending method. Based on measurements of various parameters including thermal performance, tensile strength, DC conductivity and space charge distribution, the effect of nano-graphene on thermal, mechanical and electrical properties of XLPE was thoroughly studied. Meanwhile, the nano-dielectric samples were subjected to accelerated water tree aging test to explore the potential inhibition effect of nanographene on water tree aging process of XLPE. We believe that nanographene can decrease the growth rate of water tree both by increasing the yield strength of XLPE and hindering water migration within it.27.The obtained differential scanning calorimetry (DSC) curves of graphene/XLPE samples  are shown in Fig. In Fig. The tensile strength of graphene/XLPE samples  are shown in Fig. 29. Atomistic ReaxFF and large-scale molecular dynamics simulations by Gao et al. also elucidate the ability of graphene to modify the microstructure of polymers by promoting favorable edge chemistry and polymer chain alignment30.The enhancement in tensile strength of graphene-doped XLPE samples can be attributed to the following factors: (1) the addition of graphene nanoparticles improves the microstructure of the XLPE through minimization of the size of voids/defects inside the sample, and improves the alignment of structural elements of the microstructure at all stages of XLPE sample manufacturing; and (2) the graphene serves as a reinforcing phase to further improve the mechanical properties33. In Fig. Figure 34. Therefore, it is speculated that no conducting path of charge carriers forms, resulting in the consistency of the conductivity.To explain the phenomenon, the percolation theory needs to be considered: when the graphene content is 0.01%, the fillers are well-dispersed and the nearest distance between neighbor fillers can be as large as tens micrometers, indicating the filler content is much lower than the percolation thresholdBased on PEA method described in the method section, the space charge distribution of graphene/XLPE samples  was measured, the results of which are shown in Fig. For pure XLPE samples, hetero-charges accumulated dramatically near the cathode, where only a few homo-charges appeared near the anode. Meanwhile, the density of hetero-charges increased obviously with the polarization time, whereas the density of homo-charges showed little changes.For graphene/XLPE samples, however, fewer hetero-charges accumulated near the cathode compared with pure XLPE samples. The density of hetero-charges decreased significantly with increasing graphene content, and reached the minimum at the graphene content 0.008%. In addition, the density of homo-charges in the samples also decreased gradually with the increase of the graphene content and reached the minimum value at the same graphene content, namely 0.008%.35. This explains the trend of space charge density when the graphene content is lower than 0.008%. On the other hand, as the graphene content continues to increase, the overlapping sites of the graphene-polymer interaction zones would provide low-resistance paths for electrons between molecular chains, thus accelerating the transport of electrons through chain barriers, and leading to significant amount of space charge accumulation in the bulk of polymer36. Therefore, it can be concluded that appropriate amount of graphene nano-particles can improve the space charge distribution with XLPE samples.The above phenomena show that the density of homo-charges in graphene /XLPE samples is higher than that of the pure XLPE samples. One possible reason is that the graphene-polymer interaction zones will introduce deep traps between graphene and PE, thus suppressing the charge carrier transport, leading to the accumulation of large quantities of homo-charges in the vicinity of both electrodes37. It is regarded as one of the principal aging factors of XLPE cables, as its formation in the cable will cause the reduction in breakdown voltage of cable’s insulating layer39. As a result, in the development of graphene/XLPE nano-dielectric which serves as the insulating materials of power cables, the water tree aging characteristics should also be considered.Water trees are the dendritic paths formed in a wide range of hydrophobic polymeric insulating materials when exposed to electric stress and water immersionFor this purpose, pure XLPE samples and 0.007 wt% graphene/XLPE samples were prepared and subjected to water tree aging tests, respectively. The test platform was shown in Fig. Figure In Fig. To better quantify the results of the water tree aging test, we measured the length of the water tree branches in pure XLPE slice and 0.007 wt% graphene/XLPE slice, and calculated their average value respectively. The results indicated that the average tree length in 0.007 wt% graphene/XLPE slice is 85.6 μm, significantly (16.2 μm/15.9%) shorter than 101.8 μm in pure XLPE slice. All the above experimental results indicate that graphene nanoparticles can inhibit the growth of water trees in XLPE effectively.41.To explain the inhibiting effect of graphene nanoparticles, we need to focus on the initiation and growth processes of water trees, which according to the known research, are caused by the fatigue of the material. The fatigue, meanwhile, is mainly attributed to two factors-electric stress, and chemical corrosionElectric stress induces water tree by the followings. Once water immerse the insulating material, it will deform along the direction of the electric field force, during which its shape changes from spherical to ellipsoidal. The deformed water droplets will apply the extrusion force to the material. When the pressure exceeds the tensile stress of the material, the molecular chain of the latter will break, leading to the generation of sub-micro cavities (diameter about 0.1–5 μm) and micro channels (diameter about 100 nm), as shown in Fig. On the other hand, the water tree induced by chemical corrosion mainly considers the effects of oxidation and ion electroosmosis. When water immerses the material, oxide is also introduced. The oxidation of the polymer will then happen on the wall of some isolated micro-voids, which eventually produce sub-micro cavities in the amorphous region of the material. Meanwhile, ions dissolved in the water will also migrate and cause electroosmosis effect within the material, resulting in the formation of micro channels. These channels, together with the cavities produced by the oxidation process, form the water trees within the insulating materials.42. Since the electric stress-induced water tree is closely related to the yield strength of the material, it is less likely that water trees grow in graphene/XLPE samples.Now we consider the effect of graphene nanoparticles on the above two processes. Figure Meanwhile, the hydrophobic graphene inhibits the growth of water tree also by hindering the water migration within XLPE sample. As illustrated in Fig. In conclusion, we have fabricated graphene/XLPE nano-dielectric samples by a solution method. The effect of graphene addition on the thermal performance, tensile strength, DC conductivity, space charge distribution and water tree aging behavior of graphene/XLPE composites were investigated. Results indicate that XLPE filled with graphene nanoparticles exhibited excellent mechanical and electrical insulation properties, namely higher tensile/yield strength, improved space charge distribution, and shorter water tree branches. The improvements mainly attribute to the high stiffness of graphene, deep traps introduced by interface between graphene and XLPE, and the blockage effect of graphene within XLPE. In addition, it was found that graphene nano-fillers have but limited improvement for the thermal performance of XLPE blends, mainly on crosslinking degree. The above findings provide a guide for tailoring lightweight XLPE materials with excellent mechanical and electrical performances by doping them with a small amount of graphene. The composite proves its potential for UHV HVDC cable insulation applications.3 was purchase from Kingfa Science & Technology Co., Ltd. Graphene nanoplatelets with properties shown in Table Polyethylene (PE) with a density of 0.98 g/cmBased on the above procedures, we prepared graphene/XLPE nano-dielectric samples with graphene contents by weight of 0%, 0.002%, 0.004%, 0.006%, 0.008% and 0.01%, respectively. The samples with thickness of 3 mm were subjected to thermal performance and tensile strength tests, whereas films with thickness of 500 μm were used to study the DC conductivity and space charge distribution.Additional pure XLPE samples and 0.007 wt% graphene-XLPE samples were prepared for water tree aging test. The thickness of the samples was 3 mm. On the surface of each sample, a 25 mm diameter circular area was chosen as the active aging zone, among which 18 pinholes with depths of 1.5 mm and tip radius of 4.0 ± 0.5 μm were embedded as the initiation spots of the water trees.Thermal performance of the samples was studied by using a Mettler-Toledo differential scanning calorimeter (DSC). Before the measurement, the samples were thermal-erased first, and then heated to 200 °C at a rate of 10 °C/min, during which the heat flow was recorded. Based on the result, crystallinity degree and crosslinking degree of the samples were calculated.Tensile strength of graphene/XLPE samples were investigated under the guidance of ISO 527-2012. The sample was first cut into a dumbbell shape and then subjected to tensile test on an elongation tester , at a strain rate of 30 mm/min.DC conductivities of the pure XLPE sample and graphene/XLPE samples were measured by using a three-electrode structure with a Keithley 6517B connected in series. The measurement was performed strictly in accordance with IEC 62631, under 2 kV/mm, and 25 °C, 40 °C, 50 °C, 60 °C, 70 °C, respectively.43. Samples of 500 μm in thickness and 10 cm in diameter were sandwiched between an aluminum electrode and a semiconductive polymer electrode. As the measurement started, a DC electric field of 30 kV/mm was applied to the sample and kept for 30 min. Afterwards, the depolarization current of the sample was recorded for another 1000 s.The space charge distribution was investigated by the pulsed electro acoustic (PEA) method under room temperature 25 °CAs for the water tree test, experimental platform shown in Fig. The platform mainly consists of two parts: I. high voltage generating part, and II. water tree aging part. In part I, a signal generator in series with a power amplifier was adopted to generate 7.5 kVrms voltage with a frequency of 400 Hz. The high voltage was then applied to a rod copper electrode through a water resistance (≈ 10 kΩ). In part II, the 0.007 wt% graphene/XLPE sample with a thickness of 3 mm was sandwiched by a PTEF container filled with 1.7 mol/L NaCl solution, and a grounded copper electrode. Note that a 35 mm diameter circular area was hallowed at the bottom of the container, so that NaCl solution can directly immerse the pinholes on the sample. To transmit the high voltage to the pinhole tips of the graphene/XLPE sample, the rod copper electrode was inserted into the NaCl solution. Under the co-influence of moisture and electrical stress, water trees were therefore generated at the pinhole tips of the sample.


Sarcoidosis is a systemic inflammatory disorder characterized by “noncaseating granulomas.” It primarily affects the lungs, but multiple other organs can be involved. Sarcoidosis has been increasingly reported in association with cancer. It can precede, follow or occur at the same time as the diagnosis of cancer. We report a case of sarcoidosis that was diagnosed concomitantly with colon cancer, highlighting the diagnostic dilemma of sarcoidosis vs. cancer metastasis, the relationship between the two, and the value of PET scan in follow-up and monitoring of disease activity. Sarcoidosis comes from the Greek word “Sarco,” which means flesh . It is aIn the last few decades, sarcoidosis has been increasingly reported in association with cancer. It can precede or occur at the same time of cancer diagnosis. Sarcoidosis was also reported several years after cancer diagnosis and/or flourished after initiation of chemotherapy or radiotherapy.Follow-up of sarcoidosis is complicated and depends largely on the organ involved. Symptoms, signs, and inflammatory markers are the corner stones of follow-up; however, PET scan, being a reliable method of measuring disease activity and distinguishing active granuloma from fibrosis, proves to be a useful tool.The patient was a previously healthy 49-year-old Caucasian female who presented to the hospital with abdominal pain associated with nausea, vomiting, and weight loss. CT of her abdomen showed circumferential wall thickening of the ascending colon, highly suspicious for colonic carcinoma with associated pericolic and upper abdominal lymphadenopathy and splenomegaly with several splenic hypodensities suggestive of metastases was also noted.The patient underwent laparotomy with hemicolectomy, histopathology revealed ascending colon adenocarcinoma. Five lymph nodes were positive for metastatic carcinoma and multiple sarcoidal noncaseating granulomas were also noted.PET (positron emission tomography) scan following surgery revealed mediastinal bilateral hilar lymphadenopathy and splenomegaly with marked abnormally increased metabolic activity suspicious for metastasis. Prior to her presentation, there was no chest imaging available for comparison.Splenic biopsy showed multiple granulomas with focal necrosis. Stain was negative for fungal and acid-fast microorganisms.Blood work at the time showed Ca of 9.1 mg/dl, Cr of 0.9 mg/dl, CEA level of 9.6 ng/ml, and ACE level of 45 nmol/ml/min. CRP and ESR were not checked as they could be falsely elevated in postoperative state. Given the absence of respiratory symptoms and minimally elevated serum ACE level, no treatment was deemed necessary for asymptomatic incidental sarcoidosis and the patient was started on chemotherapy to treat cancer.Two years later, a follow-up PET scan revealed increased lymphadenopathy in multiple areas including the left axilla and the left mammographic chain and mesenteric lymphadenopathy. Lesions were also noted in the liver and spinous processes of L3-L4. Progression of her splenic involvement was also noted (see Figures At that time, her CEA level had increased from 3 to 14.2 ng/ml and ACE level was >120 nmol/ml/min, ESR was>100 mm/hr, CRP was 15.5 mg/L, and Cr was 1.7 mg/dl. QuantiFERON-TB Gold and ANCA antibodies were all negative.Given the presence of biopsy-proven sarcoidosis with elevated ACE level, compatible imaging, and the fact that serum CEA can also be elevated sarcoidosis , the patRepeated PET scan showed resolution of the hilar lymphadenopathy with improvement of the left axillary and liver metabolic activity. Previously reported increased splenic and bone metabolic activity had also resolved (see Figures Sarcoidosis is a multisystemic disorder of unknown cause characterized by the presence of granulomas in different organs. Ninety-five percent of patients will present with intrathoracic involvement, and fifty percent will have extrathoracic involvement, most commonly involving the skin and eyes . GastroiDiagnosis of sarcoidosis is established when compelling clinical and radiological features are present in combination with histopathological evidence of noncaseating granulomas provided that other causes of granuloma including mycobacterial and fungal infections are excluded .Imaging plays an essential part in the diagnosis of sarcoidosis and in assessing disease severity. Chest X-ray can help the diagnosis and staging of pulmonary sarcoidosis. CT can help detect lesions in multiple parts of the body; however, newer imaging modalities like PET CT have the advantage of detecting active inflammation by measuring increased glucose metabolism in those areas. Decreased tracer uptake on subsequent PET scans in response to treatment proves PET scans to be an important tool to monitor disease activity. .The association between sarcoidosis and malignancy is a controversial topic. Sarcoidosis can precede, follow, or occur at the same time of diagnosis of cancer. A study of Danish cohorts who were followed for over thirty years showed an increased risk of cancer both short term and long term after diagnosis . A more The relationship between sarcoidosis and cancer takes many forms : the sarIt can occur as paraneoplastic syndrome related to cancer and is defined as sarcoidosis that is coincidental or diagnosed within one year of cancer diagnosis.Pathophysiological interpretation implied a potential role of cytokines and angiogenesis . Other tIn an attempt to characterize cancer cases associated with sarcoidosis, Spiekermann et al. identified 59 cases of solid tumors and sarcoidosis reported in the literature up to 2017, of which 24 cases of sarcoidosis diagnosed at the same time with malignancy . Of the In our case, sarcoidosis was diagnosed at the same time with colon cancer. Colonic lymph nodes were the first site at which sarcoidosis was discovered. It is unclear if sarcoidosis had preceded or occurred in response to colon cancer given the lack of symptoms, signs, and imaging prior to cancer diagnosis; nevertheless, the fact that her sarcoidosis was aggravated at the same time of recurrence of malignancy implies a potential role of cancer or chemotherapy in modulating sarcoidosis activity.In this case, the patient initially had mildly elevated serum ACE level with no symptoms and no signs of end organ damage, so priority was given to cancer treatment and no therapy was deemed necessary to treat sarcoidosis. However, she returned two years later with significant elevation of serum ACE level combined with evidence of kidney injury, elevated biomarkers, imaging evidence of increased metabolic activity involving the chest, abdomen, bone, liver, and spleen, and biopsy-proven sarcoidosis, almost all of which had improved or completely resolved after initiation of immune suppressive therapy except for the abdominal lymph nodes that were proved to be cancerous later on.Differentiating cancer recurrence from sarcoidosis was extremely challenging in this case, and tissue biopsy is almost always needed to rule out cancer recurrence. Follow-up of sarcoidosis can also be challenging, and testing depends largely on the organs involved. Serum ACE level is elevated in about 90% of patients and is known to be a marker of disease activity anticipated to normalize with therapy . Yet, seThis case represents a diagnostic dilemma of cancer metastasis vs. sarcoidosis and the role of PET scan to monitor disease activity and response to treatment; it also imposes a question of a potential two-way relationship between cancer and sarcoidosis.Should a patient with sudden sarcoidosis flare be screened for occult malignancy? Do patients with established sarcoidosis need to be monitored more closely after cancer diagnosis or treatment in anticipation of disease flare? The answer needs further investigation.


Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with unclear pathogenesis. IPF is considered as a risk factor for lung cancer. Compared to other lung cancers, small-cell lung cancer (SCLC) has a lower incidence, but has a more aggressive course. Patients with IPF and SCLC have a lower survival rate, more difficult treatment, and poorer prognosis.2) and etoposide (100 mg for 5 days) was initiated for both patients. Antifibrotic agents were continued during the chemotherapeutic regimen. Both patients showed improvement in their condition after treatment.Case 1 was of a 66-year-old man with IPF for 5 years, who was admitted to our hospital for dyspnea. Case 2 was of a 68-year-old woman, who presented with chest pains, cough, and dyspnea. Both patients had extremely poor lung function. High-resolution computed tomography and pathology revealed that both patients had IPF and SCLC. Chemotherapy comprising nedaplatin (80 mg/mThe favorable outcomes in these 2 cases suggests that chemotherapy is worth considering in the management of patients having SCLC and IPF with poor lung function. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that causes irreversible decline in lung function . The cha2). Treatment with glucocorticoids and pirfenidone led to improvement of the symptoms. With regular treatment, the patient’s condition continued to remain stable, as confirmed by a follow-up chest HRCT performed 5 years later. However, the follow-up scan revealed a newly developed, irregular mass in the right upper lobe and enlargement of the anterior trachea and posterior vena caval groups of lymph nodes; the lower lobes did not show any changes on either side  and etoposide (100 mg for 5 days) was then initiated. However, during the chemotherapy, the administration of antifibrotic agents was continued. After 4 courses of treatment, marked reduction of the tumor was observed. A repeat thoracic CT scan revealed reduction in the size of the shadow in the upper right lung and significant decrease in the size of the metastatic lymph nodes in the anterior tracheal and posterior vena caval groups of lymph nodes; however, there was no visible decrease in the severity of IPF  and etoposide (100 mg for 5 days) was initiated. During the chemotherapy, treatment with glucocorticoids and N-acetylcysteine was continued in order to control the symptoms and prevent the progression of fibrosis. After 6 cycles of chemotherapy, the patient’s symptoms were relieved. Follow-up CT scan revealed a reduction in the extent of atelectasis in the left upper lobe, reduction in the size of the mass shadow, and absence of mediastinal lymph node enlargement , and blood gas analysis revealed respiratory failure. Chest HRCT scans showed fibrotic changes in the lower lobes of both lungs and high-density shadows in the upper lobe of the left lung with obstructive atelectasis. Further, enlargement of the mediastinal lymph nodes was also noted Fig. a, b. ForIPF is a severe pulmonary fibrotic disease that entails a high risk of LC; to date, its etiopathogenesis remains elusive . The incIn Case 1, the patient had a history of IPF since 5 years and insisted on continuing his medication to maintain stability of his condition. In Case 2, IPF and SCLC were detected simultaneously, but the longer history of IPF could not be excluded. The coexistence of IPF and SCLC compromises pulmonary function and may lead to respiratory failure, as seen in Case 2. According to the Eastern Cooperative Oncology Group (ECOG), chemotherapy poses significant risk in patients with IPF. Therefore, before initiation of the treatment, both the patients as well as their family members were explained in detail about the risks and benefits of the treatment, and consent for the treatment was obtained. In both of our cases, the patients benefited from chemotherapy, without the exacerbation of IPF. Adverse events of chemotherapy were defined as low , as per the CTCAE v5.0.Etoposide, in combination with platinum, is a commonly used chemotherapeutic regimen with fairly good treatment outcomes. Nedaplatin is a second-generation cisplatin, with a mechanism of action similar to that of cisplatin, but lower nephrotoxicity and neurotoxicity; additionally, it does not show complete cross-resistance with any other chemotherapeutic agents used in combination with platinum . EtoposiIn conclusion, individualized treatment is necessary for the management of patients with IPF and LC. However, it is necessary to ensure the safety of treatment. Chemotherapy can be considered in patients with poor lung function due to the presence of both IPF and SCLC; however, antifibrotic agents cannot be discontinued during the treatment . Our fin