Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients with concomitant frontotemporal dementia (FTD).In order to improve current understanding of the presence and relevance of pathological pTDP-43 subtypes in ALS, the present study examined the pattern of cortical pTDP-43 aggregates in 61 ALS cases without FTD.Based on the presence, morphology and composition of pTDP-43 pathology, three distinct ALS-TDP subtypes were delineated: (1) A predominant pattern of pTDP-43 granulofilamentous neuronal inclusions (GFNIs) and grains that were immuno-negative for p62 was identified in 18% of cases designated ALS-TDP type E; (2) neuronal cytoplasmic inclusions (NCIs) that were immuno-positive for both pTDP-43 and p62 were observed in 67% of cases assigned ALS-TDP type B; and (3) scarce cortical pTDP-43 and p62 aggregates were identified in 15% of cases coined ALS-TDP type SC . Quantitative analyses revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E. Principal component analysis demonstrated significant relationships between GFNIs, grains and ALS-TDP subtypes to support the distinction of subtypes E and B. No significant difference in age at death or disease duration was found between ALS-TDP subgroups to suggest that these subtypes represent earlier or later stages of the same disease process. Instead, a significantly higher ALS-TDP stage, indicating greater topographical spread of pTDP-43, was identified in ALS-TDP type E. Alzheimer’s disease neuropathological change (ABC score ≥ intermediate) and Lewy body disease (Braak stage ≥ IV) was more prevalent in the ALS-TDP type SC cohort, which also demonstrated a significantly lower overall cognitive score.In summary, the present study demonstrates that ALS-TDP does not represent a single homogenous neuropathology. We propose the subclassification of ALS-TDP into three distinct subtypes using standard immuno-stains for pTDP-43 and p62 in the motor cortex, which is routinely sampled and evaluated for diagnostic neuropathological characterisation of ALS. We propose that future studies specify both clinicopathological group and pTDP-43 subtype to advance current understanding of the pathogenesis of clinical phenotypes in pTDP-43 proteinopathies, which will have significant relevance to the development of targeted therapies for this heterogeneous disorder.The online version contains supplementary material available at 10.1186/s40478-023-01670-2. Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease underscored by diverse yet poorly understood pathomechanisms that contribute to differential therapeutic responses and unsuccessful drug development , 2. ALS C9ORF72 gene [All cases with a pathological diagnosis of ALS-TDP were selected from a neuropathological series collected by the Sydney Brain Bank through regional brain donor programs in Sydney, Australia. The brain donor programs hold approval from the Human Research Ethics Committees of the University of New South Wales and comply with the statement on human experimentation issued by the National Health and Medical Research Council of Australia. Patients were diagnosed using standard clinical diagnostic criteria , 14–18 fF72 gene  which waF72 gene  was idenF72 gene , 23 was C9ORF72-carriers [Pathological classification was based on pTDP-43 aggregates in the motor cortex, which is the earliest cortical region implicated in ALS , 25. TDPcarriers ; and 3) carriers . In addiTen µm thick formalin-fixed, paraffin-embedded tissue sections from each region-of-interest were immunostained with antibodies against phospho-TDP-43 S409/410)  and p62  using a Ventana BenchMark GX autostainer. Both antibodies underwent 30 min antigen retrieval with CC1 reagent followed by a one hour primary antibody incubation and visualization using Optiview DAB IHC Detection Kit. Slides were digitally scanned using the Olympus VS-120 slidescanner at 20 × magnification. Regions of interest measuring 2000 µm × 1000 µm were defined and the percentage area occupied by granulofilamentous pTDP-43 inclusions, pTDP-43 grains and round pTDP-43 neuronal cytoplasmic (NCIs) were quantified using QuPath (version 0.3.2)  , which ep value < 0.05 taken as significant. Group differences were determined using a one-way ANOVA followed by Bonferroni post hoc tests for age, disease duration, postmortem delay, density of different pTDP-43 inclusions, ALS-TDP stage and ACE-III scores, and with chi-square test for gender, site of disease onset, C9ORF72 and co-pathologies. Any relationships between variables were assessed using principal component factor analysis (PCA), which included the density of different pTDP-43 inclusions in the motor cortex, ALS-TDP group, genetic mutation and demographic variables (age and disease duration).Statistical analysis was performed using SPSS (Version 28) with a Granulofilamentous neuronal inclusions (GFNI), abundant grains and oligodendroglial inclusions that were immunopositive for pTDP-43 but not p62 were identified in 18% of cases (n = 11). The morphology and composition of these aggregates resemble that recently reported in FTLD-TDP type E  and as sA predominant pattern of round neuronal cytoplasmic inclusions in superficial and deep cortical layers with relatively few dystrophic neurites were observed on both pTDP-43 and p62-immunostained sections of the motor cortex in 67% of ALS cases (n = 41). The morphology, composition and distribution of these aggregates resemble that seen in the cortical sections of FTLD-TDP type B cases and as such, these cases were designated ALS-TDP type B.Scarce pTDP-43 and p62 aggregates were observed in the motor cortex of 15% of cases (n = 9) and were designated ALS-TDP type SC . Double-labelled immunofluorescence confirmed the absence of ubiquitin and p62 immunoreactivity in the pTDP-43 aggregates of ALS-TDP type E cases . Principal component factor analysis was used to assess all relationships between variables across all cases and loading scores > 0.6 was considered significant. Two separate factors accounted for > 57% of variance. Significant relationships were identified between ALS-TDP subtype (0.74 loading), % GFNI (0.86 loading) and % pTDP-43 grains (0.83 loading) , supporting the construct that pTDP-43 GFNI and grains differentiated the ALS-TDP groups. Factor 2 accounted for 22% of the variance and showed that % round pTDP-43 NCIs (0.633 loading) associated with age (-0.63 loading), disease duration (-0.64 loading) and presence of a C9ORF72 mutation (0.69 loading). This is consistent with the shorter disease duration, younger age at death and round NCIs characteristic of type A/B described in C9ORF72 cases [Assessment of motor cortical burden of pTDP-43 morphologies revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E compared to ALS-TDP type B and ALS-TDP type SC cases  > 6.2, 72 cases .Fig. 4QuC9ORF72 expansion was identified between groups (X(2) = 2.41, p = 0.3)  = 14.49, p < 0001, Table C9ORF72-carriers and sporadic cases (age at death (mean ± SD): 59 ± 8 years in C9ORF72 cases, 66 ± 11 years in sporadic cases, p = 0.1; disease duration (mean ± SD): 2 ± 1 years in C9ORF72 cases, 3 ± 2 years in sporadic cases, p = 0.2; PMI (mean ± SD): 24 ± 10 h in C9ORF72 cases, 28 ± 15 h in sporadic cases, p = 0.5). However, a significantly higher ALS-TDP stage was identified in C9ORF72-carriers compared to sporadic ALS cases . ALS-TDP stage was similar in ALS-TDP type E cases with and without a C9ORF72 expansion .Group comparisons revealed no significant differences in age at death, age at disease onset, disease duration or post-mortem interval between groups Table . No signTo determine if the GFNIs characteristic of ALS-TDP type E represent immature pTDP-43 inclusions that have yet to coalesce into the more prevalent ALS-TDP type B morphology which is ubiquitinated, the frontal cortex, which is affected later in pathological progression (and consequently would demonstrate comparatively “earlier” pathology by the end of the disease progression) were assessed. ALS-TDP type B cases with pTDP-43 pathology in the frontal cortices (n = 21) demonstrated similar round neuronal cytoplasmic inclusions with few neurites that were immunopositive for p62 in these “later affected” regions. As expected, all ALS-TDP type E cases demonstrated GFNI and grains in the frontal cortex that were consistent with that seen in the motor cortex of these cases. Regional differences in pathological subtypes were not identified within cases here nor have they been previously reported Fig. . In the C9ORF72 expansion), 46% of the ALS-TDP type B cohort  and 44% of the ALS-TDP type SC cohort , with no significant group differences in the years between assessments and death (Table p < 0.05) .ACE-III scores  were avaThe present study examined and reports, for the first time, three distinct histological subtypes in ALS cases without FTD: (1) In 18% of cases, a predominant pattern of pTDP GFNIs and grains, which were immuno-negative for p62 were identified, and these cases were designated ALS-TDP type E; (2) In 67% of cases, a predominant pattern of round NCIs that were immuno-positive for both pTDP-43 and p62 were observed, and these cases were designated ALS-TDP type B; (3) In 15% of cases, scarce cortical pTDP-43 and p62 aggregates were observed, and these cases were coined ALS-TDP type SC .Quantitative analyses identified a significantly greater burden of pTDP-43 GFNIs and grains in ALS-TDP type E. PCA analysis of pTDP-43 inclusion morphologies revealed significant associations between GFNIs, grains and ALS-TDP subtypes to support that these pathologies segregate with ALS-TDP type E. No significant difference in age of disease onset, death or survival was found between groups to suggest that these subtypes represent earlier or later-stage disease pathologies. Further to this, pTDP-43 morphology and pattern of p62-immunoreactivity in each case was consistent across early- and late-affected cortical regions, indicating that non-ubiquitinated GFNIs are not a predecessor to ubiquitinated NCIs. Instead, a significantly higher ALS-TDP stage was identified in the ALS-TDP type E cohort. Interestingly, a lower overall cognitive score and higher incidence of Alzheimer’s disease neuropathological change (≥ intermediate level) or LBD (Braak stage ≥ IV) was identified in the ALS-TDP SC cohort. To date, pathological subclassification of pTDP-43 subtypes is routinely performed in FTLD, as demonstrated by the nomenclature “FTLD-TDP subtypes A-E”. Given the similarities in the pattern of cortical pTDP-43 in two of our ALS subgroups with that identified in the FTLD-TDP subtypes, we have adopted the same alphabetised subclassification and propose that future studies consider specifying clinicopathological group followed by pTDP-43 subtype (eg. FTLD-ALS type E) to advance pathomechanistic understanding of clinical phenotypes in pTDP-43 proteinopathies.Widespread pTDP-positive p62-negative GFNI, grains and oligodendroglial inclusions were first described in seven FTD cases with motor neuronal pTDP-43 and rapid disease durations of one to three years . This paIn contrast to a previous study that assessed the inclusion morphologies in the ~ 30% of ALS cases with pTDP-43 in the hippocampus , this stC9ORF72 expansion was identified in ALS-TDP subtypes B and E but not subtype SC here. Although this may be considered basis for support of a B-E continuum, it is important to note that in FTLD, the C9ORF72 expansion is predominantly associated with subtypes A and B [C9ORF72 expansion has also been associated with FTLD-TDP subtypes A + B and E [C9ORF72-type B cases, indicating greater topographical spread of pTDP-43 to extramotor regions. Perhaps surprisingly, this was not associated with lower overall cognitive scores in either of these cohorts although it is worth noting that cognitive assessments were performed midway in the disease process. Importantly however, ALS-TDP stage is an indicator of regional presence, not severity [The  A and B , 37–39.  A and B , 33, 40. B and E , highligseverity , 41. Intseverity , it is uIn summary, the present study delineates three distinct histological subtypes in ALS-TDP cases according to the presence, morphology and composition of cortical pTDP-43 pathology. These pathological subtypes demonstrate no significant difference in age at death or disease duration to suggest that they capture an earlier or later cross-sectional process in pathological pTDP-43 development. Rather, they are associated with different motor cortical burden of GFNIs and grains, topographical spreads, overall cognitive performances and co-pathologies to suggest the involvement of divergent pathomechanisms in ALS-TDP. Given the similarities between two of these ALS-TDP subtypes with that seen in FTLD-TDP, we have adopted the same alphabetised classification and highlight the need for further research to elucidate whether these similar subtypes identified in different clinical phenotypes share common disease pathways. As such, we propose that future studies specify both clinicopathological phenotype and pTDP-43 subtype, which will be important for the advancement of current understanding of disease pathogeneses and the development of targeted therapies for pTDP-43 proteinopathies.Additional file 1: Supplementary Figure 1.


This study investigates energy harvesting by a deionized (DI) water droplet flow on an epitaxial graphene film on a SiC substrate. We obtain an epitaxial single-crystal graphene film by annealing a 4H-SiC substrate. Energy harvesting of the solution droplet flow on the graphene surface has been investigated by using NaCl or HCl solutions. This study validates the voltage generated from the DI water flow on the epitaxial graphene film. The maximum generated voltage was as high as 100 mV, which was a quite large value compared with the previous reports. Furthermore, we measure the dependence of flow direction on electrode configuration. The generated voltages are independent of the electrode configuration, indicating that the DI water flow direction is not influenced by the voltage generation for the single-crystal epitaxial graphene film. Based on these results, the origin of the voltage generation on the epitaxial graphene film is not only an outcome of the fluctuation of the electrical-double layer, resulting in the breaking of the uniform balance of the surface charges, but also other factors such as the charges in the DI water or frictional electrification. In addition, the buffer layer has no effect on the epitaxial graphene film on the SiC substrate. Graphene is a monolayer crystal with carbon atoms in a honeycomb structure that has been intensively investigated for various applications because of its extraordinary carrier mobility and chemical stability . GraphenOver the past decade, the number of sensor devices connected to the Internet has increased. These “Internet of things (IoT)” devices can be used anywhere, such as monitoring a person with a pacemaker, pastured livestock, and traffic control . As the However, the origin of such energy-harvesting processes remains unclear. Various mechanisms for nanocarbon-based energy-harvesting devices based on solution flow have been proposed, such as the momentum transfer by phonon , breakin2 bonds without defects and dislocations. Furthermore, protein and amino acid adsorption on the epitaxial graphene film generally shows electron doping , respectively. The carrier-type change is typical of H2 intercalated epitaxial graphene films [Typical Raman spectra of the epitaxial graphene film before and after Her layer  and not ubstrate . The forne films . These r2 intercalation for the parallel and perpendicular electrode configurations were 63 and 46 mV, respectively, which were similar to those before H2 intercalation, indicating that the buffer layer under the epitaxial graphene film was not influenced by energy harvesting from the solution flow.A summary of the voltage generated by 50 measurements using DI water flow is shown in The dependence of the generated voltage on the droplet amount in the epitaxial graphene film with the buffer layer is shown in As shown in The origins of energy harvesting by solution droplets flowing on the graphene film differ as mentioned in the introduction. A key interpretation is the significance of the existence of anions and cations as well as the broken uniform balance of surface charges in graphene by the electrical double layer in the moving solution droplet . TherefoBecause epitaxial graphene films on the SiC substrate used in this study were single crystals with large areas with no polymer residue, ideal results were expected for graphene-based devices. Therefore, the energy harvested by the solution flow on the graphene surface must not be anions or cations in the solution. Hence, the electrical double layer is inessential in this case.The generated voltages depended on the number of DI water droplets as shown in This study investigated energy-harvesting characteristics of single-crystal epitaxial graphene films synthesized on SiC substrates using DI water flow. A voltage as high as 100 mV was generated by the DI water flow, and the generated voltage was independent of the electrode configurations parallel and perpendicular to the DI water flow as well as the existence of the buffer layer under the epitaxial graphene film. The average electrical power of energy harvesting by the DI water flow exceeded 1 µW. The epitaxial graphene film-based energy-harvesting devices using solution flow can be used for electrical power supply to IoT devices in the presence of flowing water, such as river or seashore, with no electrode configuration in the direction of water flow.


In a discovery cohort, we found significantly higher mortality in patients with IPF who had elevated platelet counts within the normal range. However, our validation cohort did not confirm this observation, despite significantly increased platelets, neutrophils, active TGFβ1, and CCL5, a chemokine produced by inflammatory cells, in the blood, lung, and bronchoalveolar lavage (BAL) of patients with IPF. In vivo, we showed that despite platelets being readily detected within the lungs of bleomycin-treated mice, neither the degree of pulmonary inflammation nor fibrosis was significantly different between TGFβ1fl/fl.PF4-Cre and control mice. Our results demonstrate for the first time that platelet-derived TGFβ1 does not significantly mediate inflammation or fibrosis in a PF animal model. Furthermore, our human studies revealed blood platelet counts do not consistently predict mortality in IPF but other platelet-derived mediators, such as C-C chemokine ligand 5 (CCL5), may promote neutrophil recruitment and human IPF.Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFβ1, although the role of these cells in IPF is ill-defined. In this study, we investigated whether platelets, and specifically platelet-derived TGFβ1, mediate IPF disease progression. Patients with IPF and non-IPF patients were recruited to determine platelet reactivity, and separate cohorts of patients with IPF were followed for mortality. To study whether platelet-derived TGFβ1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGFβ1 in megakaryocytes and platelets  is unclear. We identified that patients with IPF have significantly more platelets, neutrophils, and active TGFβ in their airways than control patients. Using an animal model of IPF, we demonstrated that platelet-derived TGFβ does not significantly drive lung fibrosis or inflammation. Our findings offer a better understanding of platelets in both human and animal studies of IPF. Interstitial lung diseases (ILDs) consist of over 200 inflammatory and fibrotic diseases affecting the lung interstitium , with idTransforming growth factor-β1 (TGFβ1) has a plethora of biological roles ranging from inflammation through fibrosis  and wountgfb are associated with IPF disease progression  of patients with IPF , and mougression . Fibroblgression . Howeverproposed –14. IdenPlatelets are key mediators in immunity and tissue remodeling and represent an abundant source of TGFβ1, which can be released rapidly on cell activation . The rolThe role of platelets in chronic respiratory conditions such as IPF is now actively being pursued . It has Platelets and neutrophils act in a synergistic manner to cross the endothelium during inflammation in vitro and in vivo . Along wDespite the growing body of evidence demonstrating the increased presence of activated platelets in clinical and animal studies of IPF, it is still unclear how platelets drive fibrotic disease progression and whether platelets represent a major source of profibrotic TGFβ1 in IPF. Therefore, in this study we sought to define whether platelets, and more specifically, platelet-derived TGFβ1, mediate IPF disease progression using both clinical patient samples and an animal model of pulmonary fibrosis.fl/fl.PF4-Cre mice were obtained from Prof. Richard Hynes , BALF or lung biopsies from male and female healthy controls, patients with IPF or non-ILD, were collected with written informed consent and research ethics committee approval (IRAS study I.D. 29531). For survival analysis, male and female patients with IPF from the University College London Hospital (UCLH) or Exeter ILD Services were followed prospectively for mortality based on blood platelet counts as described in Supplemental Methods (ethics study number REC reference 18/L0/0937). Blood platelet counts from a cohort of male and female patients with IPF or healthy controls were obtained from the UK Biobank (applications 9072 and 44046). Patient demographics are shown in n = 6–12). BAL cells were stained with anti-CD61 antibody  or mouse IgG1 isotype control , and percentage of CD61+ platelets in BALF (n = 3–6) was quantified on a BD FACSVerse flow cytometer  and analyzed with FlowJo v10 software .Patient BALF and plasma were collected and processed as described in Supplemental Methods. Cell counts were performed on cytospun BALF (n = 4–5), plasma (n = 10–37), and BALF (n = 7–16) using ELISA kits . Active TGFβ1 was quantified by a Mink lung epithelial cell (MLEC) bioassay , and total matrix metalloproteinase-7 (MMP7) were quantified in PRP (bioassay  as descrn = 4) were added to the top of 8 μm PET trans-wells  and chemoattractants: 100 nM N-formylmethionine-leucyl-phenylalanine (fMLP) (Sigma-Aldrich), 1 ng/mL TGFβ1 (R&D systems), 10 ng/mL leukotriene B4 (LTB4)  or PRP added to the bottom. After 1 h at 37°C, cells that had migrated toward the chemoattractant in the bottom chamber were counted on a BD FACSVerse flow cytometer.Human or murine neutrophils and PRP were isolated as described in Supplemental Methods. In brief, untreated, 1 μM SB-525334 , 10 μM Galunisertib  ALK5 inhibitors or DMSO vehicle pretreated neutrophils  were randomized into treatment or control groups. The treatment groups were given 25 or 50 IU bleomycin  in a volume of 50 μL 0.9% saline by oropharyngeal instillation. The control group was given 50 μL 0.9% saline by oropharyngeal instillation. Mice were monitored for disease severity and culled at 6, 21, and 28 days post instillation. Individual mice were coded for each experiment to allow for blinded result assessments and data analysis.Male and female TGFβ1BALF was obtained from murine lungs by three washes with 1 mL PBS. BALF was centrifuged and cell pellet was processed for cytospin cell counts. Murine lungs were homogenized in PBS before red blood cell lysis. Cells were blocked with Fc block  and stained with anti-Ly6G-PE , anti-CD11b-APC , and anti-CD11c-APC-H7  antibodies. Cells were analyzed on a BD FACSVerse flow cytometer and FlowJo software.Dehydrated murine lungs were scanned on a SkyScan-1072 micro-CT scanner and images were reconstructed using SkyScan NRecon software . The degree of fibrosis in the lungs was assessed using InForm image analysis software  as previously described . Total lMurine or human lungs were processed for histological analysis as described in Supplemental Methods. Immunohistochemistry (IHC) was performed for murine  or human CD61 . Sections were scanned on a Nanozoomer Digital Slide Scanner and analyzed using NDP.view software . Quantification of collagen deposition in alveolar walls based on modified Martius Scarlet Blue (MSB) staining was performed using Orbit Image analysis software .U test, unpaired t test, one- or two-way ANOVA with Holm–Sidak post hoc testing were performed with Prism v9 software . Cox proportional hazard modeling, with multivariate analysis using mortality data of patients with IPF, was conducted using OriginLab statistical software. Unless stated otherwise, means ± SE are shown in all graphs with a P < 0.05 considered significant.All experiments were conducted with at least three technical replicates. For neutrophil experiments, three to four biological replicates were used to minimize donor variability. All statistical analyses with the Gehan–Breslow–Wilcoxon test, linear regression, Mann–Whitney 9/L) and lowest in those with the lowest platelet counts . In addition, data from the UK Biobank revealed that patients with IPF had significantly higher blood platelet blood counts than healthy controls (P < 0.01).We initially sought to investigate the role of platelets in IPF disease progression. A discovery cohort of consecutive, unselected patients with IPF  from UCLCox proportional hazard modeling with multivariate analysis was conducted to further investigate any potential correlations with mortality in the UCLH and Exeter patient cohorts. In both the UCLH and Exeter cohorts, higher percentage in forced vital capacity (FVC) was found to be significantly protective (probability for hazard ratio was 0.005 for UCLH cohort and 0.0001 for Exeter cohort). In addition, age at diagnosis was found to offer protection in the Exeter cohort, but not in the UCLH patient cohort . Cox proportional hazard modeling based on sex or platelet counts did not show any significant correlation with mortality in either patient cohort. These findings suggest that although blood platelet counts do not consistently predict IPF disease progression or survival, patients with IPF have significantly more platelets in their blood than healthy controls.P = 0.044). In addition, we found no correlation in the levels of total or active TGFβ1 with blood platelet counts from patients with IPF    was usedcontrols A, confirfl/fl.PF4-Cre mice had regained initial weight loss with no significant difference between bleomycin-treated littermate or TGFβ1fl/fl.PF4-Cre mice . HPLC analysis for hydroxyproline (a major component of collagen) content in whole lungs (Following 21 days after bleomycin (50 IU) treatment, littermate and TGFβ1Cre mice B. No difCre mice B. To detCre mice  revealedCre mice C. A trenobserved D and E ble lungs F confirmfl/fl.PF4-Cre animals did not differ , the percentage weight loss between littermate and TGFβ1t differ A. Micro-t differ B and C. t differ D. No difanalyzed E. This s+ platelets and platelet aggregates were found within IPF lung, particularly in the blood vessels , indicating that platelet-derived TGFβ1 does not affect neutrophil counts at baseline in naïve mice. During the peak of inflammation at day 6, littermate and TGFβ1fl/fl.PF4-Cre mice treated with bleomycin lost significantly more weight than saline-treated mice . This suggests that although platelet-derived TGFβ1 influences neutrophil migration in vitro, it does not significantly drive cellular recruitment into the lung or airways in vivo.To address whether platelet-derived TGFβ1 can influence cellular recruitment during pulmonary inflammation in vivo, littermate or TGFβ1ted mice A. Signifted mice B–E. HoweCre mice C–E. FlowCre mice F–I. BleoCre mice I, with eCre mice I. To ver+ platelets in BALF  , on IPF Recent evidence has proposed the lung as a major site for platelet biogenesis in mice with a distinct megakaryocyte subset, residing within the lung interstitium . In addifl/fl.PF4-Cre lungs; however, the degree of fibrosis was equivalent in both treatment groups, suggesting that platelet-derived TGFβ1 is redundant in this animal model of PF. Of importance, it should be noted that although bleomycin remains the gold standard animal model for PF research, it does not fully recapitulate the human disease. The degree of lung fibrosis in mice is dependent on bleomycin dose  or APB5 (a PDGFR-β blocking antibody) attenuates bleomycin-induced PF , a European Commission FP7 award PIEF GA-2012–326928 to C. Rebeyrol, and a GW4 BioMed MRC Doctoral Training Partnership award to A. Duckworth.No conflicts of interest, financial or otherwise, are declared by the authors.D.L.W.C., C.J.S., and J.C.P. conceived and designed research; D.L.W.C., T.A.M., J.S., C.R., H.S.G., H.L.B., M.H., E.K.D., R.J.J., A.A.K., A.D., M.L., and C.J.S. performed experiments; D.L.W.C., T.A.M., J.S., E.K.D., and A.D. analyzed data; D.L.W.C., T.A.M., J.S., E.K.D., C.J.S., and J.C.P. interpreted results of experiments; D.L.W.C. and T.A.M. prepared figures; D.L.W.C. and T.A.M. drafted manuscript; D.L.W.C., T.A.M., J.S., C.R., H.S.G., H.L.B., M.H., E.K.D., R.J.J., A.A.K., A.D., M.L., C.J.S., and J.C.P. edited and revised manuscript; D.L.W.C., T.A.M., J.S., C.R., H.S.G., H.L.B., M.H., E.K.D., R.J.J., A.A.K., A.D., M.L., C.J.S., and J.C.P. approved final version of manuscript.


Self-administration was characterized under Progressive Ratio (PR) and Fixed Ratio (FR) 1 schedules of reinforcement in 3 h sessions. THC decreased IVSA of oxycodone in a FR procedure but increased reward seeking in a PR procedure. CBD decreased the IVSA of oxycodone in the FR but not the PR procedure. The results are consistent with an anti-reward effect of CBD but suggest THC acts to increase the reinforcing efficacy of oxycodone in this procedure.Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as potential therapeutics for the non-medical use of opioids. In these studies female rats, previously trained to self-administer oxycodone (0.15 mg/kg/infusion) intravenously in 6 h sessions, were allowed to self-administer oxycodone after exposure to cannabidiol (CBD) and Δ It is difficult to experimentally determine if cannabis reduces opioid use in humans, but animal models can assist in distinguishing pro-reward from anti-abuse effects.Reduction of opioid use concomitant with cannabis use  may aris9-tetrahydrocannabinol (THC) reinstates beer- and sucrose-seeking behavior in rats, for example  reduces alcohol or cocaine seeking behavior in rats when applied via a dermal gel , aged 10–11 weeks on arrival in the laboratory in a single cohort of 20. The vivarium was kept on a 12:12 hour reversed light-dark cycle, and behavior studies were conducted during the vivarium dark period. The animals were pair housed and food and water were provided ad libitum in the home cage and in the self-administration chambers. Experimental procedures were conducted in accordance with protocols approved by the Institutional Animal Care and Use Committee of the University of California, San Diego and consistent with recommendations in the NIH Guide .Two animals were lost due to mechanical failure of vivarium equipment prior to the start of intravenous self-administration (IVSA) training. Three other animals were lost to the study prior to the start due to catheter/implantation complications . One animal was discontinued for self-injurious behavior (paw chewing) after Session 27. Five animals were discontinued due to loss of catheter port integrity after Sessions 22, 31, 53, 54, and 64, respectively. The nine at the end of the study included 5 original THC group animals and 4 original Vehicle group animals.2.2Vapor inhalation was conducted as previously described  with the2.3Female rats were implanted with intravenous catheters and trained to self-administer oxycodone (0.15 mg/kg/infusion) on a Fixed Ratio (FR) 1 schedule of reinforcement using methods previously described . In this2.42.4.1j)–5  before the 34th and 35th sessions in a counter-balanced order. The 36th and 37th sessions were conducted under PR, without any pre-session treatment. The per-infusion dose of oxycodone was changed to 0.06 mg/kg/inf for Sessions 38–41 and the rats were injected with either Veh or THC  before the 39th and 40th sessions in a counter-balanced order. For analysis, the day following the injection days was used as the no-injection comparison.On sessions 33–37 animals were tested on a Progressive Ratio (PR) procedure with 0.15 mg/kg/infusion oxycodone available. In the PR paradigm, the required response ratio was increased after each reinforcer delivery, within a session  as deterj)–5 . In this2.4.2For Sessions 42–64, rats were permitted to self-administer oxycodone in 3 h sessions under a FR1 contingency. In Sessions 43–45 the oxycodone dose  was varied in a counter-balanced order.The study next evaluated injection of 0, 5, 10 and 20 mg/kg of THC, i.p., prior to oxycodone (0.06 mg/kg/infusion) self-administration sessions, assessed in a counter-balanced order in Sessions 48–51.IVSA was then suspended for a week between Sessions 53 and 54 to permit assessment of the acute effects of THC  on rectal temperature and nociception assays.Self-administration of oxycodone was returned to the original training dose (0.15 mg/kg/infusion) in 3 h sessions (FR1) for Sessions 56–64. Rats were exposed to cannabidiol (CBD) vapor (400 mg/mL in the PG) or vehicle (PG) vapor for 30 minutes immediately prior to IVSA sessions in a counter balanced order for Sessions 59–60. Two additional animals were discontinued due to catheter failure, thus N=10 . Vapor inhalation was selected because we have previously reported effects of CBD on body temperature via this route  that wer2.4.3Then rats were returned to the PR response contingency (0.15 mg/kg/infusion) for Sessions 65–69 and exposed to vehicle (PG) vapor, CBD vapor (400 mg/mL in the PG) or THC vapor (100 mg/mL in the PG) for 30 minutes immediately prior to IVSA sessions in a counter balanced order for Sessions 66–68. Thereafter the oxycodone dose was increased to 0.30 mg/kg/infusion for Sessions 70–74 and the PG, CBD and THC pre-exposure conditions repeated in a counterbalanced order in Sessions 71–73. For Sessions 75–77 the dose of oxycodone  was altered in a counterbalanced order, with no pre-treatment. One individual’s catheter exhibited resistance to daily flushing in this experiment and was non-patent by the final experiment and was therefore excluded from analysis. Rats completed PR sessions with no pre-treatment at the 0.03 mg/kg/inf dose for Sessions 78–83, and at the 0.06 mg/kg/infusion dose for Session 84.2.4.4Rats (N=9) were returned to FR1 in 3 h sessions with the oxycodone dose 0.06 mg/kg/infusion for Sessions 85–88. Rats were exposed to PG vapor, or CBD vapor  for 30 minutes immediately prior to IVSA sessions in a counter balanced order for Sessions 86–88. One rat had a catheter that failed patency during this study and was therefore excluded.2.5Infusions obtained, the percentage of responses directed at the drug-associated lever, total correct responses and breakpoints (for Progressive Ratio) were analyzed by ANOVA, or by mixed-effect models where there were missing values. Within-subjects factors of Dose or Pre-treatment were included where relevant. In our approach a single priming infusion is delivered if no responses have been made within 30 minutes of session initiation under FR (this is not included for PR). These are rare after the initial few sessions of acquisition and are thus reported qualitatively where present, but not formally analyzed. In all analyses, a criterion of P<0.05 was used to infer that a significant difference existed. Any significant main effects were followed with post-hoc analysis using Tukey (multi-level factors), Sidak (two-level factors) or Dunnett (to assess change relative to one of the Treatment Conditions.) correction. All analysis used Prism for Windows .3.3.1This experiment showed that THC  increases breakpoints reached by female rats in the progressive ratio procedure , confirmThe impact of THC was statistically indistinguishable across oxycodone unit doses  as there was no significant effect of oxycodone Dose nor an interaction of Dose with Treatment Condition. The post-hoc Dunnett test of the marginal mean confirmed significantly lower breakpoints were reached in the No-Injection condition compared with the THC condition, across oxycodone Dose.3.2The lack of difference between breakpoints generated under the different oxycodone unit doses prompted a comparison under FR1 conditions (3 h sessions to match the maximum duration of the PR sessions), to determine if these were functionally different doses in IVSA. This demonstrated that the 0.15 mg/kg/infusion dose resulted in fewer infusions obtained  reduced the number of infusions obtained in comparison with PG vapor inhalation or a session in which there was no exposure prior to the IVSA session  under FR1 because the oxycodone dose did not alter self-administration of oxycodone under a PR procedure. The one-way ANOVA confirmed a significant impact of oxycodone Dose  on infusions obtained and the Tukey post hoc further confirmed significant differences between all doses .Because CBD did not alter oxycodone IVSA under a PR procedure, we re-determined the impact of CBD vapor under FR1 to rule out a potential development of tolerance to the CBD. For this we tested two CBD vapor doses (100 and 400 mg/mL) and the 0.06 mg/kg/infusion dose of oxycodone. The one-way ANOVA confirmed a significant impact of Pre-Treatment condition  on infusions obtained and the Tukey post-hoc further confirmed significantly fewer infusions were obtained after CBD 400 exposure compared to PG exposure .4.9-tetrahydrocannabinol (THC) increases female rats’ oxycodone seeking under a Progressive Ratio schedule, while it reduces oxycodone self-administration under a Fixed Ratio 1 (FR1) contingency. Our previous study was conducted in male rats and while several conditions of oxycodone IVSA were evaluated, it was all conducted with a FR1 schedule of reinforcement  and the present study found that the effect of FR vs PR reinforcement schedule on the impact of THC extended to oxycodone IVSA in female rats. The increased behavioral output  in the PR procedure associated with THC  in a PR procedure, nor any interaction of the effect of THC with heroin unit dose, in that study. Therefore, the prior results were quite similar to the impact of unit dose of oxycodone across FR1 and PR procedures in the current study.It was somewhat unexpected that rats reached similar breakpoints for 0.06 and 0.15 mg/kg/infusion in the PR under control conditions  given an apparent difference across this dose range that was observed in prior work with male rats trained in sessions of 1 h or 12 h duration . In partOne of the strengths of this study was that animals were originally trained in extended access (6 h) sessions, examined for this study in 3 h sessions under both FR1 and PR response contingencies and exhibited a high degree of behavioral stability across an extended number of sessions. This enhances comparison of findings across the experiments. In general, this confirms ongoing work from multiple laboratories showing that oxycodone is a typical opioid reinforcer in rat intravenous self-administration, and that stable self-administration patterns are produced in short-access IVSA in male and female rats . SimilarIn contrast with THC, the impact of CBD was to reduce oxycodone seeking under FR1 and to leave it unaffected under the PR1 contingency. CBD has been previously shown to have anti-drug-seeking effects in rats  when delInterestingly, the inhalation of vapor from cannabis extracts with high CBD content (64.2% CBD and 7.1% THC) decreased fentanyl IVSA under a FR, but not a PR, schedule in rats with and without induced neuropathic pain . InteracIn conclusion these studies provided additional evidence that THC reduces oxycodone seeking under easy-access conditions because it enhances the rewarding value of a unit dose of oxycodone. When access requires more work in a PR procedure, THC increases oxycodone seeking responding. In contrast, the effect of CBD was to decrease oxycodone self-administration in easy access conditions but to have no effect in harder access conditions. This cautions that cannabis is not necessarily reducing addiction liability in association with any observed reduction in oxycodone intake.


The deep subsurface is, including subsurface groundwater, one of the last unknown frontiers to humankind. A significant part of life on Earth resides in the deep subsurface, hiding the great potential of microbial life of which we know only a little. The extreme conditions in deep terrestrial subsurface, such as anoxia and oligotrophy, high salinity, lack of primary production, are thought to resemble those of early Earth, which makes this environment an analog for studying early life in addition to possible extraterrestrial life in ultra-extreme conditions. Furthermore, deep subsurface microorganisms offer possibilities for novel biotechnological applications.Much new knowledge has been gained over the last decade describing the microbial communities in different terrestrial deep biospheres. The previous Research Topic . Giovannelli et al. presents a new view of sampling strategy to study ecological features over a greater geological gradient for a broad-scale analysis of the subsurface microbial ecosystem in contrast to studying very specific sites. However, laboratory incubations should not be forgotten, as shown by Nuppunen-Puputti et al. and Mandal et al., where different microbial physiologies were revealed by enrichment cultivation, which might not have been detected otherwise. The challenge now is to elucidate the activity and functional properties of the microbial communities and to connect the biological data to that of the geological to link microbial diversity to microbial functions in the very inaccessible deep terrestrial subsurface. With this Research Topic, we aimed to collect new knowledge about the roles and functions of microbial communities in the undisturbed or disturbed subsurface and called upon our colleagues to step up to the task. The deep subsurface is of interest worldwide and the present Research Topic include samplings from Asia, South America, North America, and Europe!The present Research Topic covers the important field of geomicrobiological research of constructed deep geological sites, such as spent nuclear fuel repositories containing metals and bentonite clay  and long-term microcosms studies that enable us to manipulate the environmental conditions  would allow us to close the gap in our current knowledge of the activity and functional properties of the microbial communities, and to connect the biological data to that of the geological to link microbial diversity to microbial functions in the very inaccessible deep terrestrial subsurface. The slow turnover time of deep biosphere microorganisms is reflected also in the studies of this Research Topic, with experimental times ranging from several months  to several years .The deep subsurface biosphere is one of the largest microbial ecosystems on Earth, but many fundamental questions about how life exists and thrives in this habitat are still unanswered. We know only little about the biochemical processes of the deep Earth's crust, or the microbial communities interacting with biotic and abiotic factors in the isolated aquifers or the ability of the microbial communities to adapt to changing environments. This is due much to the high costs, inaccessibility, and challenges of direct sampling of deep environments and to the fact that many deep biosphere microbial populations grow very slowly or are so-called resistant to laboratory culturing techniques. To overcome the access and cost challenges, Nuppunen-Puputti et al. Sessile and planktic bacterial communities were studied in microcosms containing Finnish groundwater  and mica schist from the same site. The microcosms were spiked with different carbon substrates, and it was shown that the microbial communities differed between microcosm types and sessile and planktic communities. Especially, sulfate-reducing bacteria were frequent occupiers of the rock surfaces. Although the sessile and planktic bacterial communities differed in their community structure, some sort of metabolic cooperation likely exists between them and with the fungal communities.The importance of studying both sessile and planktic microbial communities in the deep biosphere was demonstrated by Mandal et al.; Nuppunen-Puputti et al.). Mandal et al. noted a better response of rock-hosted community toward carbon dioxide vs. bicarbonate amendment. They propose that these endolithic microorganisms could show great potential for answering the fundamental questions of deep life and their exploitation in carbon dioxide capture and conversion to useful products.Inorganic carbon or low-molecular-weight carbon  links multiple biogeochemical pathways and thus represents an important carbon and energy source for microorganisms in the deep crystalline bedrock . The microcosms without additional substrates developed the lowest bacterial community richness compared to acetate, methane, or methanol-amended mesocosms . Methanol supported the richest bacterial and fungal communities. Especially the Hydrogenophaga/Serpentinomonas attached to the rock surface had a significant response to methanol.A pulse of low-molecular-weight carbon compounds in the beginning of a long-term microcosm incubation supported epilithic community development on mica schist . Corrosion of metallic waste container materials by anaerobic microorganisms, most commonly sulfate-reducing bacteria, originating from porewater or groundwater has long been considered a major risk factor for long-term safety. Burzan et al. didn't find direct evidence of sulfate reduction within bentonite or of microbially induced corrosion of the carbon steel, unlike previously reported in the case of the crystalline bedrock environment.Deep geological repositories are considered in many countries as the most promising solution for the safe and long-term disposal of hazardous wastes. The ability of deep biosphere microorganisms to influence the environmental conditions or material integrity in deep geological repositories has remained a topic of interest due to the potential impact on the long-term safety of these repositories. In many repository concepts the spent nuclear fuel is packed in metal containers immersed in bentonite clay buffer, which when fully expanded will contain an internal pressure that will hinder microbial growth and movement toward the waste containers. There remains still much to learn about the size of the microbial communities, the genetic variation and metabolic functions in the deepest part of the biosphere despite the advancements during the past decade. Our understanding of how deep biosphere microbes react to changing environments, be it nutrient availability or constructed environment, has greatly advanced. Shifting the focus from only the planktic community to cover also the sessile community and studying the long-overlooked fungal community in addition to better-known bacterial and archaeal communities have advanced our understanding of the diversity and functionality of the deep biosphere. Advancement in sampling techniques and access to geographically and geologically diverse sites has been crucial in building new knowledge. Still, studying the deep biosphere remains a privilege of few and more accessible and innovative sampling and laboratory scale techniques are needed.Both authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Flash-induced porous graphene (FPG) was synthesized via a broad-spectrum flash lamp that induced synergistic photo-effects between ultraviolet and visible-near-infrared wavelengths, resulting in large-area synthesis in just a few milliseconds.−1 was produced, exhibiting low density (0.0354 g cm−3) and outstanding absolute electromagnetic interference shielding effectiveness of 1.12 × 105 dB cm2 g−1.A hollow pillar graphene with low sheet resistance of 18 Ω sqA lightweight, flexible, and high-throughput FPG is applied for electromagnetic interference shielding of a drone radar system and the human body.The online version contains supplementary material available at 10.1007/s40820-023-01157-8. 2-size porous graphene with a hollow pillar structure in a few milliseconds. The resulting material demonstrated low density (0.0354 g cm−3) and outstanding absolute EMI shielding effectiveness of 1.12 × 105 dB cm2 g−1. The FPG was characterized via thorough material analyses, and its mechanical durability and flexibility were confirmed by a bending cycle test. Finally, the FPG was utilized in drone and wearable applications, showing effective EMI shielding performance for internal/external EMI in a drone radar system and reducing the specific absorption rate in the human body.Porous 2D materials with high conductivity and large surface area have been proposed for potential electromagnetic interference (EMI) shielding materials in future mobility and wearable applications to prevent signal noise, transmission inaccuracy, system malfunction, and health hazards. Here, we report on the synthesis of lightweight and flexible flash-induced porous graphene (FPG) with excellent EMI shielding performance. The broad spectrum of pulsed flashlight induces photo-chemical and photo-thermal reactions in polyimide films, forming 5 × 10 cmThe online version contains supplementary material available at 10.1007/s40820-023-01157-8. With the advent of future mobility and wearable electronics, various electronic components including sensors, actuators, processors, and controllers are integrated with cloud computing, big data, and 5G wireless communication for autonomous driving, intelligent robotics, and real-time healthcare –3. The hA variety of composites have been developed for soft and lightweight EMI shielding materials by incorporating conductive fillers such as metal nanomaterials , 10, MXeRecently, light-material interactions have attracted a great deal of attention because they can activate transient, multi-physical, and spatiotemporally controlled reactions –23 to st2, N2 and CO gases were released from the PI film surface, resulting in large area (5 × 10 cm2) hollow pillared graphene with a low density of 0.0354 g cm−3 in a few milliseconds (ms). The synthesized FPG showed outstanding absolute EMI SE of 1.12 × 105 dB cm2 g−1 due to its low sheet resistance (18 Ω sq−1) and multiple internal scattering. To confirm the FPG formation mechanism, the chemical/structural changes were thoroughly analyzed by using various characterization methods, such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction (XRD). The feasibility of the FPG growth was verified by theoretically calculating the heat distributions of the PI film, which exhibited sufficient surface temperature (up to 2300 ℃) for graphene synthesis. The synthesized FPG was applied for aerospace and wearable applications, including drones and the human body. In a drone radar system, the lightweight FPG film successfully replaced conventional heavy metal jigs by shielding EMI from multi-stacked printed circuit boards (PCBs) and external noise signals. For wearable applications, the FPG effectively reduced the specific absorption rate (SAR) of the human body by 80.3% per 1 g of tissue and also lowered the magnitude of EM waves penetrating the human body by ~ 9.88 dB.Herein, we report a flash-induced porous graphene (FPG) synthesis method to achieve a high-throughput, outstanding performance, lightweight, and flexible EMI shielding film for drones and wearable applications. The ultraviolet (UV) range of the broad spectrum flashlight led to the breaking of chemical bonds in polyimide (PI) molecules which subsequently created defects for effective light absorption in the visible-near-infrared (Vis–NIR) wavelengths. The photothermal heat generated by the Vis–NIR region caused graphene synthesis while CO−2 and 1–10 ms, respectively. The fluences were measured using an energy meter for different lamp power and pulse widths. The single irradiation area was set at 5 cm × 10 cm with a square mask for edge clearance. The stage was moved along the Y-axis to obtain a large area FPG of 10 cm × 10 cm. The lamp power, pulse width, irradiation frequency, and stage moving speed were adjusted to be 9 W cm−2, 4 ms, 1 Hz, and 100 mm s−1, respectively.Commercial polyimide films  were used for the experiments. PI films were cleaned using ethanol and de-ionized water in an ultrasonic bath. Photo-pyrolysis of the PI film was performed using a flash lamp  under ambient conditions. The wavelengths of the flash lamp range from 250 to 1100 nm  and the wavelengths are tuned using an optical pass filter . The lamp power and pulse width were adjusted in the ranges of 1–16 W cm2) used in the simulation were given by the COMSOL material library. The heat generation per volume from absorbed light was calculated by Eq. (−1. X-ray diffraction (XRD) analysis was conducted using a RIGAKU Ultima IV with Cu Kɑ radiation (λ = 1.54 Å). The sheet resistance was characterized using a four-point probe . A vector network analyzer  and waveguides were used to measure scattering parameters (S11 and S21) of the material in the 18–26.5 GHz (K-band) frequency range at room temperature. The EMI SE value was calculated using the given equations :–36:34–36entclass1pt{minimaquations –40:3\docR, SEA, and SET are reflection, absorption, and total EMI SE, respectively. The effective absorbance (Aeff) is calculated to evaluate the absorption potential of materials. The home-built moving stage was used for bending the FPG.T, R, and A represent the transmission, reflection, and absorption coefficients, respectively. SEA K-band frequency-modulated continuous wave (FMCW) radar on a drone (Pixhwak) operating from 23 to 25 GHz was used to verify the EMI shielding properties for a machine . As show2 area by controlling the position of the probe antenna, as shown in Fig. S2 [The internal EMI from the RF transceiver board was observed using an open-ended probe antenna OEW-42). The 2-dimensional electric fields radiated from the RF transceiver PCB were measured in a 20 × 20 cm. The 2-d Fig. S2 . The antTo verify the EMI shielding performance for a human body, the SAR was measured . As show2, N2, and CO gases are released by dissociation of C=O, C–N, and C–O bonds [sp3) transforms into stacked, ordered graphene sheets (sp2). This process results in the formation of porous graphene, a crystalline structure of carbon atoms partially arranged in a hexagonal lattice [Figure –O bonds , 55. Car–O bonds –58, the  lattice . The syn−2. As displayed in Figs. To confirm the synergistic photo-effects, the full wavelength, and the Vis–NIR wavelength by blocking UV of the flash lamp were individually irradiated on the PI film with lamp fluence of pristine, 8, 12, 14, 18, and 22 J cm2 FPG manufactured by irradiation of a flash twice with a beam area of 5 × 10 cm2. The SEM image in the inset of Fig. sp2 carbons. These are more likely to form the hexagonal graphene structure than other precursors, which primarily generate amorphous carbon.To achieve effective EMI shielding in various applications such as future mobility and wearable devices, a large-area EMI film should be fabricated with high productivity. Figure Due to its high thermal stability, PI is not greatly affected by temperature conditions. However, if the temperature is artificially raised to preheat the PI, it could potentially enhance the speed of the photo-reaction, which could in turn affect the rate of gas emission and the pore expansion time . The fla2. The difference in production time was negligible in the small area of 10 × 10 mm2, while a significant decrease of more than 66.5 times was confirmed in large areas of 100 × 100 and 200 × 200 mm2. Figure S7 shows the calculation method and Table S1 presents the detailed calculation results. Note that the flash can dramatically increase productivity by increasing the size of the lamps and chamber, or by application to roll-to-roll processes. Table S2 shows comparison of porous graphene formation method of this work with previously reported light-induced method. These results suggest that the flash lamp is a suitable light source to fabricate a porous graphene-based EMI film with a large area and high productivity.Figure −2. As depicted in Fig. −2, with heat transfer occurring at roughly 100 µm depth within the PI. These results indicate that the necessary temperature for graphene formation can be achieved using lamp irradiation. Figure −2. As the lamp fluence increased, ~ 5 µm-sized micro-pores began to form and were finally synthesized into porous structural walls that were hundreds of nanometers wide. To further characterize the porous structure, we verified the pore size by lamp fluence, as shown in Fig. S8. As the lamp fluence increased from 18 to 24 J cm−2, the pore size increased from approximately 1.4 to 19.2 µm.To confirm whether a temperature of 1700 °C, necessary for graphene formation, can be achieved using a lamp, we conducted a COMSOL simulation to evaluate the maximum temperature and temperature distribution at various depths. Theoretical calculations were performed to determine the thermal distribution within a 125 µm-thick PI under various flash fluences ranging from 6 to 26 J cms, 397 eV for N 1s, and 532.5 eV for O 1s, which correspond to the main elements of carbon, nitrogen, and oxygen on the surface of the FPG [−1 indicating the stretching and bending modes of C–O, C–N, and C=O bonds. After lamp irradiation, a broad absorption spectrum ranging from 1000 to 1700 cm−1 was observed. At a fluence of 22 J cm−2, the peak associated with C=O, C–O, and C–N noticeably decreases. The XPS and FTIR results demonstrate that the carbon content becomes dominant due to the gas release accompanied by a decrease in nitrogen and oxygen content [The chemical changes and structural characteristics were analyzed via XPS, FTIR, Raman spectrum, TEM and XRD to demonstrate the synthesis mechanism of micro-holes and porous materials. Figure  the FPG . As the  the FPG . Results content .−1, respectively [−2, the 2D peak was observed. The inset graph shows the ratios of ID/IG and I2D/IG Raman peaks, which indicate defects in graphene materials and the number of layers in graphene [ID/IG decreases from 1 to 0.8, and the ratio of I2D/IG increased from 0 to 0.38. The I2D/IG ratio of 0.38 indicates the formation of 4–5 layers of graphene [Figure ectively . In partectively –74. As tgraphene , 76. As graphene . Figure graphene . The crygraphene . The Ramgraphene , 79. Tab−2. Vertically aligned porous hollow pillar structures were formed because the pores expanded and grew in the direction perpendicular to the surface where the gas was released. The thickness of the hollow pillar FPG was formed to ~ 62 μm from the 125 μm thick PI film at a fluence of 22 J cm−2. Figure S11 shows cross-sectional images for thickness measurement. The SEM image in Fig. Figure −1 while the thickness increased from 26 to 92 µm. As the lamp fluence increased, the electrical conductivity also increases, as shown in Fig. S12. Based on these results, the EMI SET of the FPG was evaluated at a frequency range from 18 to 26.5 GHz, the K-band mainly used for 5G/6G communications, as shown in Fig. T was continuously enhanced over the entire frequency range. Figure S13 depicts the EMI SE measured in the C-band (4 to 8 GHz), with the measured results confirming SE performance of over 20 dB, comparable to the K-band.High EMI shielding properties of porous graphene can be achieved by low sheet resistance and high thickness which enables enhancement of the surface reflection and internal absorption, respectively –82. FiguT of the FPG, the EMI shielding performance of SER and SEA as well as the power coefficient were measured. Figure R, SEA, and SET of the FPG under various fluences of 12, 14, 18, 22 and 24 J cm−2. As the fluence increased, SET rose from 12.9 to 34 dB, and SEA also elevated from 9.1 to 27.8 dB, while SER consistently remained below 7 dB. These results confirm that SEA primarily drove the increase in SET. Figures Aeff and power coefficients , which are used to explain the EMI shielding mechanism of the FPG. Throughout the fluence range from 12 to 24 J cm−2, the R values were always higher than the A values. As the fluence increased, R values increased gradually while A and T values decreased, indicating that surface reflection plays a more significant role than absorption and that lower resistance induced by lamp fluence leads to higher surface reflection. The absorption and reflection are the two main mechanisms influencing EMI shielding. Among these, reflection is enhanced by high electrical conductivity, leading to increased reflection of EM waves and, consequently, a larger R coefficient. In shielding materials where reflection dominates [R significantly increases and the T decreases, the A may decrease according to Eq.  and a high absolute EMI SE of 1.12 × 105 dB cm2 g−1 by the porous structure. The FPG retained 1.4 and 0.86 times its initial sheet resistance and SE performance, respectively, even after 10,000 bending tests. The FPG, effectively shields internal and external EMI of a drone radar system, reduces the radiated electric field (− 10.8 dB) and antenna gain (− 12.2 dB), and detects radar signals without saturation. In wearable applications, the FPG reduced SAR by 80.3% and 77.8% for indoor and outdoor frequencies, respectively, satisfying the IEEE standard. We believe that the proposed lightweight, flexible, and highly productive FPG will be effective in resolving diverse EMI shielding issues for future mobility and wearable applications.In summary, we developed a novel high-throughput synthesis technique of flash-induced porous graphene via synergistic photo-effects for EMI shielding. Flash irradiation with a broad spectrum causes a series of photoreactions in the PI film by simultaneously absorbing UV and Vis–NIR wavelengths, leading to the synthesis of porous graphene over a large area in a few milliseconds (ms). The UV wavelengths within the full spectrum induce defects in the PI film, which enhance the absorption of Vis–NIR wavelengths and promote photothermal reactions, resulting in the synthesis of porous graphene. The XPS and FTIR results demonstrate that the carbon content becomes dominant due to the gas release accompanied by a decrease in nitrogen and oxygen content. Raman spectra, XRD and TEM images show the formation of multilayer graphene through the rearrangement of carbon atoms in a disordered carbon matrix. At a lamp fluence of 22 J cmSupplementary file1 (PDF 2048 kb)Below is the link to the electronic supplementary material.


Two-dimensional (2D) materials and their vertically stacked heterostructures have attracted much attention due to their novel optical properties and strong light-matter interactions in the infrared. Here, we present a theoretical study of the near-field thermal radiation of 2D vdW heterostructures vertically stacked of graphene and monolayer polar material (2D hBN as an example). An asymmetric Fano line shape is observed in its near-field thermal radiation spectrum, which is attributed to the interference between the narrowband discrete state (the phonon polaritons in 2D hBN) and a broadband continuum state (the plasmons in graphene), as verified by the coupled oscillator model. In addition, we show that 2D van der Waals heterostructures can achieve nearly the same high radiative heat flux as graphene but with markedly different spectral distributions, especially at high chemical potentials. By tuning the chemical potential of graphene, we can actively control the radiative heat flux of 2D van der Waals heterostructures and manipulate the radiative spectrum, such as the transition from Fano resonance to electromagnetic-induced transparency (EIT). Our results reveal the rich physics and demonstrate the potential of 2D vdW heterostructures for applications in nanoscale thermal management and energy conversion. Radiative heat transfer between two objects in far-field contexts is bound by Stefan Boltzmann’s law of the black body. However, when the separation distance is less than the characteristic wavelength predicted by Wien’s law, the near-field radiative heat transfer is significantly enhanced due to photon tunneling of evanescent waves, exceeding the blackbody limit by several orders of magnitude, especially when the material supports surface wave resonances (such as surface plasmon polaritons and surface phonon polaritons) ,2,3. In Two-dimensional (2D) materials provide an excellent platform for the enhancement and manipulation of near-field thermal radiation due to their strong light-matter interactions in the infrared and have been attracting considerable attention in the last decade, including graphene ,23,24,25Graphene and 2D hBN, with the same crystal structure and naturally small lattice mismatch, are considered fundamental building blocks for 2D heterostructures. Graphene supports surface plasmon polaritons ,23,24 anIn this paper, we investigate the near-field thermal radiation of 2D vdW heterostructure vertically stacked by these two single-layer materials, focusing on the radiative spectral properties. We have demonstrated the contribution of the coupling between broadband plasmons in graphene and narrowband phonon polaritons in 2D hBN to the near-field radiative heat transfer and found an asymmetric line shape in the spectra, and confirmed it to be a Fano resonance arising from the interference between the continuum state (plasmons) and the discrete state (phonon polaritons). The Fano resonance has been widely discovered in spectra of various photonic nanostructures ,46 as weWe assume that the 2D vdW heterostructures are suspended, i.e., free-standing without a supporting substrate, that the lateral dimensions are much larger than the characteristic thermal wavelength so that the finite size effect can be neglected, and that the thicknesses are negligible. Let us assume that they lie on the  formula :(1)QT1,Tp- or s-polarization) of the incident and reflected electromagnetic waves. In this paper, only symmetric structures of cold and hot sides are considered, so Here, given by ,50:(2)TωIn this paper, all materials are non-magnetic, then The 2D vdW heterostructure in this study is considered as a random stack of monolayer graphene and 2D hBN, and neglecting thickness, its effective conductivity can be obtained by simply adding the conductivities of the two components : σeff=σGitten as :(5)σD=iωHere, given by :(7)σ2D-hken from ,43: τ−1=The real and imaginary parts of the optical conductivity of graphene and 2D hBN as a function of frequency are plotted in Based on the previous theoretical formalism, we performed numerical calculations of the near-field thermal radiation using MATLAB code.To understand the near-field thermal radiation of 2D vdW heterostructures, we first separately calculated the near-field radiative characteristics of graphene and 2D hBN. In For the case of graphene, two bright bands shown in the low-frequency region σE=D2The optical property and plasmonic behavior of graphene can be modulated by changing the chemical potential through chemical doping or electrical gating. In As the chemical potential of graphene increases PWhen the detuning frequency is 0, i.e., The preceding section primarily addressed the spectra of energy transfer functions In To conclude, 2D vdW heterostructures can achieve the same high radiative heat flux as graphene, yet with a markedly different spectral distribution, particularly at high chemical potentials.The previous considerations are mainly for suspended 2D vdW heterostructures; although it can be synthesized experimentally , it is mFor simplicity, we first consider non-dissipative substrates with constant dielectric constants For practical dissipative substrates, each substrate requires separate analysis because the optical response and the physical mechanism that interacts with the 2D vdW heterostructure are different for various materials . As an example, we use the widely used SiC as a substrate for illustration, as shown in , three parts of the bright band give rise to three peaks, with a valley at the frequency The plasmons in graphene are coupled to the surface phonon polaritons of SiC and the 2D phonon of 2D hBN. Hence, in the contour plot of 3 and LiNbO3 [In this paper, we have shown that near-field thermal radiation of 2D vdW heterostructure can be significantly enhanced and modulated by tuning the chemical potential of graphene . In d LiNbO3 , which hIn this paper, we investigate the near-field thermal radiation of 2D vdW heterostructures vertically stacked of graphene and monolayer polar material (2D hBN as an example). We show an asymmetric Fano resonance in the radiation spectrum resulting from the interference between a broad continuum of surface plasmon polaritons (SPPs) in graphene and a narrow discrete state of 2D phonon polaritons in 2D hBN. In addition, we show that 2D van der Waals heterostructures can achieve nearly the same high radiative heat flux as graphene but with markedly different spectral distributions, especially at high chemical potentials. By tuning the chemical potential of graphene, we can actively control the radiative heat flux of 2D van der Waals heterostructures and manipulate the radiative spectrum, such as the transition from Fano resonance to electromagnetic-induced transparency (EIT). Our results highlight the great potential of 2D vdW heterostructures to enhance and manipulate near-field thermal radiation, which may pave the way for highly efficient thermal management or design and optimization of energy conversion devices, such as thermophotovoltaics.


After the original 15-item Drive for Muscularity Scale developed by McCreary et al. in 2004, a more theoretically based scale that replicates the original DMS subscales with a better conceptual clarity and a shorter number of items, i.e., the DMS-9, has recently been developed by Chaba et al. in 2018. We sought to contribute to the literature especially under the Arab context, by investigating the psychometric properties of an Arabic translation of the DMS-9 in a sample of Arabic-speaking Lebanese university students of both genders.University students  from multiple universities in Lebanon were invited to fill the survey in this cross-sectional designed study (December 2022 and January 2023). Our sample was chosen using the snowball technique; a soft copy of the questionnaire was created using google forms software, and an online approach was conceived to proceed with the data collection.Using an Exploratory Factor Analysis-to- Confirmatory Factor Analysis strategy, we found that the original two-factor model of the DMS proposed in the parent study was adequately replicated in our sample. The two DMS-9 factor scores showed very good McDonald’s omega values (ω > 0.8). Findings also showed that gender invariance was achieved at the configural, metric, and scalar levels. Additionally, drive for muscularity scores correlated in the expected way with other study variables, providing support for the convergent and divergent validity of the Arabic DMS-9. Specifically, we found that greater drive for muscularity attitudes and behaviors significantly correlated with more severe muscle dysmorphic symptoms, inappropriate eating attitudes, muscle bias internalization, and lower body appreciation.Findings preliminarily suggest that the Arabic DMS-9 is psychometrically sound and suitable tool to assess the drive for muscularity construct among Arabic-speaking community adults. Making the Arabic DMS-9 available will hopefully benefit the scientific community working in Arab settings, promote local and international research in this area, and offer descriptive data on how drive for muscularity may interfere with health indicators in the general Arab population. Drive for muscularity is defined as a desire to develop a visible muscular physique by both increasing muscle mass and decreasing body fat, in order to achieve a muscular upper body and a narrow waist –3. StrivNo gold-standard measure of the drive for muscularity exists . SeveralSince its development, the DMS has been translated in different languages and adapted to different countries and languages, including Spanish , 24, ItaAlthough the 15-item DMS has been widely validated and extensively used in diverse research and clinical settings, and the findings that it relates to different relevant constructs  , this orTo date, no Arabic validation of the DMS exists to the best of our knowledge. Although research on disordered eating and body image disturbances has been widely developed in the Western world, the generalized globalization and westernization contributed to a rise in prevalence rates of these manifestations in people from non-Western cultures even exceeding those seen in Western people , 45. ResThrough the present study, we sought to contribute to the literature especially under the Arab context, by investigating the psychometric properties of an Arabic translation of the short 9-item DMS in a sample of Arabic-speaking Lebanese university students of both genders. As mentioned above, we chose the DMS-9 because of its better conceptual clarity and good psychometric qualities . Besides2 (SD = 4.12), ranging from 14.52 to 50.78 kg/m2. Most participants had a university level of education (88.8%).University students  from multiple universities in Lebanon filled the survey. Participants had a mean age of 24.46 years (SD = 6.60), ranging from 18 to 60 years and had a mean self-reported body mass index (BMI) 23.68 kg/mOther sample characteristics are displayed in Table Our sample was chosen using the snowball technique; a soft copy of the questionnaire was created using google forms software, and an online approach was conceived to proceed with the data collection (December 2022 and January 2023). The study’s main aims and goals, in addition to instructions for filling the questionnaire, were conveyed online for the participants, prior to their participation. Later, initial participants were asked to recruit other participants they know, preferably as diverse as possible regarding place of habitat within the Lebanese governorates. The questionnaire was anonymous and took between 15 and 20 min to complete. There were no credits received for participation. Inclusion criteria for participation included being of a resident and citizen of Lebanon of adult age. The “remove duplicates” option in excel ensured that the same answers were not submitted more than once. After providing digital informed consent, participants were asked to complete the instruments described below, which were presented in a pre-randomized order to control for order effects.The short form of the DMS-9 scale (9 items) was used in this study . ParticiThis scale is composed of 14 items scored on a 7-point Likert Scale . Higher scores indicate higher levels of muscularity bias internalization . This scnever) to 5  (score range 10–50) [Validated in Arabic , 64, thie 10–50) . Higher never) to 3  (score range 0–21). Higher total scores reflect greater disordered eating attitudes. In the present study, McDonald’s ω was 0.80 in the total sample.Participants were asked to complete the EAT-7, which has recently been validated in Arabic . This 7-Validated in the Arabic language , this scParticipants were asked to provide their demographic details consisting of age, gender, marital status, highest education level, self-reported height and weight to calculate the BMI, household crowding index  and phyThe DMS scale was translated to the official Arabic language, which is written and spoken across the Middle East and North Africa (MENA). The translation was performed with the purpose of achieving semantic equivalence between measures in their original and Arabic versions following international norms and recommendations . To thisThere were no missing responses in the dataset. To examine the factor structure of the DMS, we tested the original models proposed by McCreary et al.   was needed to perform the EFA according to Comrey and Lee . EFA wasCFA was conducted via the SPSS AMOS v.29 software using the maximum Likelihood estimation. The minimum sample size to conduct a CFA ranges from 3 to 20 times the number of the scale’s variables . TherefoTo examine gender invariance of DMS-9 scores, we conducted multi-group CFA  using SPComposite reliability in both subsamples was assessed using McDonald’s ω, with values greater than 0.70 reflecting adequate composite reliability . To asseThe fit indices of the one- and two-factor structure of the DMS-15 conducted in males and one-factor structure in females did not show appropriate fit Table .Consequently, we decided to conduct the EFA-CFA strategy to the DMS-9 items.2(36) = 1941.4, p < .001, and KMO (0.865) indicated that the DMS items had adequate common variance for factor analysis. None of the items had an MSA value < 0.5 and none of the items appeared repeatedly in different doublets; therefore, all items were kept in the analysis. The results of the EFA revealed two factors, which explained 81.44% of the common variance (item-factor loadings ≥ 0.62). The WRMR value was also adequate , indicating good fit of the model.Bartlett’s test of sphericity, χThe fit indices of the two-factor model of the DMS-9 scale  showed gMcDonald’s omega values were 0.90 for Factor 1 (Muscularity Behaviors) and 0.92 for Factor 2 (Muscularity body Dissatisfaction).The fit indices in Table Higher Muscularity behaviors and Muscularity body dissatisfaction scores were significantly associated with more muscle bias internalization, muscle dysmorphic disorder and inappropriate eating attitudes, and lower body appreciation Table .The present study was conducted with the aim of making available an Arabic psychometrically sound measure to assess drive for muscularity, i.e. the short 9-item DMS. The Arabic version was found to have excellent psychometric properties in terms of factorial structure, internal consistency, gender invariance, and convergent/divergent validity. These findings preliminarily suggest that the Arabic DMS is a simple, easy to use, and economic self-report scale for the reliable and valid assessment of drive for muscularity among Arabic-speaking community people.Using an EFA-to-CFA strategy as recommended in the literature , we founThe two DMS-9 factor scores showed very good McDonald’s omega values (ω > 0.8), higher than the 0.70 threshold value of good internal consistency suggested by previous researchers , 97, thuFinally, DMS-9 scores correlated in the expected way with other study variables, providing support for the convergent and divergent validity of the Arabic version of the scale. Specifically, we found that greater drive for muscularity attitudes and behaviors significantly correlated with more severe muscle dysmorphic symptoms, inappropriate eating attitudes, muscle bias internalization, and lower body appreciation. These results align with previous evidence. Similar evidence for validity of the DMS-9 through the same patterns of correlations with these variables has previously been reported in other validation studies . In addition, future cross-national validations in samples from different Arab countries are required to provide support to the cross-cultural validity of the scale. Finally, other important psychometric properties have not been addressed in this paper  and should be verified in future research.Through this study, we provide a brief, valid, economic and useful tool to evaluate drive for muscularity in Arabic-speaking men and women. Making the Arabic DMS-9 available will hopefully benefit the scientific community working in Arab settings, promote local and international research in this area, and offer descriptive data on how drive for muscularity may interfere with health indicators in the general Arab population.