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Samples were divided into three groups: 13 normal prostate tissues, 11 prostate cancer tissues with Gleason score > 7 and 10 prostate cancer tissues with Gleason score ≤ 7. Enriched regions were defined via an Enrichment Score (ES)-based sliding window approach using RINGO software , then the binding sites were annotated to human genes using the ENSEMBL database. Importantly, we selected genes whose enrichment score was greater than 1.5 in the promoter regions. Among the 21,000 genes analyzed in human 2X400K, we calculated the average of H3K27me3 modifications among patients in each group. We identified an average of 386 genes with H3K27me3 marks in the promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. These results suggested that there are more extensive H3K27me3-enriched gene promoters in advanced disease than normal tissues.
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To list enriched-genes, we performed a hierarchic clustering analysis that also helped to see similarities between patients. The genome-scale H3K27me3 profile of each group was then compared. Figure 1 showed the enrichment of genes such as IFIH1, RCN1, XRN2, EIF2B, RP11-156P1.3 and AC079305.11. However, differences at the genetic and molecular level could explain by the interindividual difference in control group. Interestingly, all of these genes are shared with all patients in GS ≤ 7 group. Despite interindividual variability, we identified one gene that is specific to GS ≤ 7 group, TRA2A gene (Fig. 2).Fig. 1Hierarchical clustering on a set of 13 normal biopsies. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles Fig. 2Hierarchical clustering analysis of tumor tissues with Gleason score ≤ 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues and rows represent the genes. The dendogram represents overall similarities in patient profiles
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Hierarchical clustering on a set of 13 normal biopsies. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles
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| 99.94 |
Hierarchical clustering analysis of tumor tissues with Gleason score ≤ 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues and rows represent the genes. The dendogram represents overall similarities in patient profiles
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| 99.94 |
The greatest changes occurred in GS > 7 group where we observed several H3K27me3-enriched genes such as MGMT, SLC4A4, ABHD2, PAPOLG, NSF, ING3, TMPRSS6, FNDC3B (Fig. 3).Fig. 3Hierarchical clustering analyses of patients with Gleason score > 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles
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Hierarchical clustering analyses of patients with Gleason score > 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles
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| 99.94 |
Discriminant analysis on the whole microarray dataset showed a clear segregation of samples with GS ≤ 7, GS > 7 and healthy controls. This analysis indicated that H3K27me3 profiles could classify prostate cancer patients (Fig. 4).Fig. 4Factorial discriminant analysis (FDA) of microarray-based genome-wide H3K27me3 profiles derived from prostate biopsies. Prostate biopsies were obtained from healthy patients (n = 13), prostate cancer patients with Gleason score ≤ 7 (n = 10) and prostate cancer patients with Gleason score > 7 (n = 11). Data showed a well-defined separation between patients according to Gleason score and H3K27me3 markers. Center of gravity for each group is reported as the empty symbol. G1, healthy group; G2, prostate cancer with Gleason score ≤ 7; G3 prostate cancer with Gleason score > 7
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Factorial discriminant analysis (FDA) of microarray-based genome-wide H3K27me3 profiles derived from prostate biopsies. Prostate biopsies were obtained from healthy patients (n = 13), prostate cancer patients with Gleason score ≤ 7 (n = 10) and prostate cancer patients with Gleason score > 7 (n = 11). Data showed a well-defined separation between patients according to Gleason score and H3K27me3 markers. Center of gravity for each group is reported as the empty symbol. G1, healthy group; G2, prostate cancer with Gleason score ≤ 7; G3 prostate cancer with Gleason score > 7
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Even though the global pattern of enriched genes in carcinoma tissues and normal tissues showed variability between patients, it was possible to identify differentially H3K27me3-enriched genes involved in prostate cancer based on enrichment score level. Using ANOVA, we identified genes that were significantly enriched between both tumor groups versus normal samples. The significance of the enrichment score values of ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes are shown in Table 2. Association of H3K27me3 enrichment and clinico-pathological variables like stage and PSA level did not show any significance. However, only Gleason score correlated with the H3K27me3 enrichment on genes (Fig. 5).Table 2Compiled statistics of FDA and ANOVA resultsGene nameCoordinate axis 1Coordinate axis 2 p valueSignificance ALG5/EXOSC8 0.815−0.1540.001** CBX1 0.6430.0790.038* GRID2 0.6550.0560.034* GRIN3B 0.627−0.1680.039* ING3 0.0740.7480.020* MYO1D 0.666−0.1680.023* NPHP3-AS1 0.640−0.1860.031* MSH6/FBXO11 0.3660.5610.047* SND1 0.1870.6530.049* SPATS2 0.579−0.3520.031* TENM4 0.5920.3200.032* TRA2A 0.563−0.4120.025*Coordinate axes refer to FDA data values (Fig. 4). P value refers to ANOVA data. *<0.05 **< 0.01Differentially H3K27me3-enriched genes in prostate cancer tissues compared to normal biopsies Fig. 5Factorial discriminant analysis. The results represent differentially H3K27me3-enriched genes between prostate cancer tissues versus normal tissues. The Highly enrichment correlated with GS > 7
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There is a pressing need for further work on the molecular mechanisms underlying prostate cancer in order to improve prognosis, diagnosis and treatment. In particular, characterizing the functional role of genetics in prostate cancer by observing the new target gene would help identify potential drugs. Here we report a set of target genes that interact with H3K27me3 in prostate cancer.
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Comparison of the H3K27me3 profiles of prostate cancer tissues versus normal tissues revealed an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. These data characterize H3K27me3 as an epigenetic feature of histone methylation-related prostate cancer progression. For the study design and criteria used here, patients were pooled at every stage analyzed to reduce the number of non-common genes. This pooling brought together individuals showing the lowest disparity of results in each group. The goal was to identify common genes that may be significant and representative of any disease stage.
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Note that TRA2A gene was shown to discriminate control group and GS ≤ 7 group. TRA2A plays a role in the regulation of pre-mRNA splicing after phosphorylation and binding to specific RNA [21, 22]. This gene has not been studied yet in connection with prostate tumorigenesis. Furthermore, TRA2A appeared to be H3K27me3-enriched in all patients and could thus serve as an epigenetic marker for early prostate cancer screening. In contrast, GS > 7 patients showed high H3K27me3 enrichment at the TRA2A promoter compared to both the GS ≤ 7 and normal groups, suggesting its major role in prostate cancer.
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FBXO11, ING3 and CBX1 genes all play a role in epigenetic control and regulation of chromatin. FOBXO11 is an arginine methyltransferase that symmetrically dimethylates arginine residues. A recent study in epithelial cancer demonstrated cells that FBXO11 induced an increase of Snai1 and a decrease of E-cadherin to prevent tumor progression, thus characterizing FBXO11 as a tumor suppressor . H3K27me3 enrichment on the FBXO11 promoter may mediate the repression of this gene in prostate cancer.
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The other tumor suppressor gene characterized here was ING3. This inhibitor of growth-family protein was initially identified as a tumor suppressor with altered regulation in a variety of cancer types, including in colorectal cancer cells [24, 25]. ING is, however, a protein involved in chromatin remodeling. In fact, ING3 acts as a reader of epigenetic code through specific recognition of H3K4me3 and can affect HAT and HDAC activity by serving as members of the Sin3A, Tip60 or Moz/Morf HAT complexes . Our results showed the epigenetic regulation of ING3 via H3K27me3 in prostate cancer suggesting putative tumor suppressor gene silencing by histone methylation in prostate cancer. These data suggest that the ING3 locus may locate in bivalent domains marked by both H3K27me3 and H3K4me3 and that ING3 may thus play a critical role in cancer development.
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CBX1 (HP1α) is a member of the heterochromatin protein 1 family (HP1s) that plays a role in the formation and maintenance of heterochromatin. This gene encodes a non-histone protein that is able to bind to histone proteins via methylated lysine residues. Genome-wide localization analysis reveals H3K27me3 binding at CBX1 promoter regions and thus points to heterochromatin formation corresponding to gene silencing in prostate cancer. It has already been shown that CBX1 is downregulated in invasive breast cancer cells , and our findings show that a novel epigenetic mechanism might involve CBX1 in transcriptional regulation, thus providing new insight for further elucidation of the molecular mechanisms causing the CBX1 downregulation in cancer cells.
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Other genes found to be H3K27me3-enriched in prostate cancer tissues compared to normal tissues include MYO1D, TENM4, GRIN3B, all of which are involved in cell communication and cell adhesion [28–30]. These genes have not yet been described in human cancer, but disrupted intracellular adhesion is a prerequisite for tumor cell invasion and metastasis.
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Furthermore, MSH6 gene was found to be epigenetically regulated in prostate cancer. MSH6 is DNA mismatch repair genes. The loss-of-function DNA mismatch repair genes are linked to mutation or epigenetic silencing . In addition, the hypermutated subtype of prostate cancer is chiefly due to loss-of-function mutations in MSH6 in advanced prostate cancer . We thus hypothesized that transcriptionally-repressed MSH6 gene might be related to H3K27me3 epigenetic modification in prostate cancer.
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The comparison of normal and tumor prostate samples revealed far more H3K27me3 marks in advanced tumor tissues compared to normal tissues. These alterations could have major impacts on global gene expression via chromatin state. Our observations suggested that H3K27me3 marks are active in tumor tissues. Increased H3K27me3 marks could be explained by the activity of the PcG such as EZH2, which is frequently over-expressed in prostate cancer [13, 33]. These results implied that the most numerous epigenetic changes from normal tissues to prostate cancer tissues were gains of H3K27me3 marks.
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Although the results reported here cannot confirm a repressor status on the increase of H3K27me3 marks on genes, they can serve to formulate a hypothesis. Performing qPCR to validate the selected differentially-enriched genes would help gauge the reliability of the ChIP-on-chip data reported here. Chromatin accessibility could be analyzed by ChIP-qPCR with RNA polymerase II. A previous study had shown that combinations of histone marks, for example gain of H3K4me3 and loss of H3K27me3 or gain of H3K27me3 and loss of H3K4me3, were strongly associated with up-regulated and down-regulated genes in prostate cancer cells. Nevertheless, gain or loss of just one mark is unlikely to prove sufficient for transcriptional changes .
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The findings of this study provide key insight for elucidating the regulation of epigenetic changes in prostate cancer. We demonstrated that global H3K27me3 histone modifications correlated with Gleason score in prostate cancer. A set of epigenetic markers was identified, and the data suggests a complex interplay between EZH2 and H3K27me3 histone modifications.
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Exercise always stimulates a temporary change in redox balance towards a more oxidized state since active skeletal muscle cells continuously produce reactive oxygen and nitrogen species (ROS, RNS), as part of metabolic processes involving increased oxygen consumption . Free radicals produced during exercise provoke a “hormetic” adaptive response to physical activity that is highly muscle fiber-specific and also positively modulate several physiological functions, such as cell signaling, immune response, and apoptosis [2, 3]. However, duration, intensity, and mode of exercise appear to affect differently the oxidative stress balance, and this may be dependent on age, gender, individual fitness levels, and nutritional status . In particular, while regular exercise induces the upregulation of antioxidant as well as oxidative damage repairing systems [2, 5], acute exercise (“vigorous physical activity”) triggers a massive generation of ROS and RNS, also by anaerobic metabolism, with depletion in antioxidant defenses, and produces oxidative damage to proteins and DNA and secondary inflammation due to the phagocytic activity of immune cells [3, 6, 7]. These events result in varying degrees of mechanical and metabolic stress on the human body, finally leading to an impairment in cell and tissue functions . Indeed, it is well known that oxidative stress is involved in the pathogenesis of hypertension, atherosclerosis, diabetes, and cancer and also accelerates aging process [9, 10].
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review
| 99.9 |
The ROS-induced adaptive response following regular long-term training leads the upregulation of the antioxidant enzymatic systems, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) that act synergistically with nonenzymatic antioxidants, that is, vitamins C and E, reduced glutathione, thiols, lipoic acid, and metallothioneins, to buffer the negative effects of oxidative stress [2, 11]. However, evidence has been provided by several investigations that exercise may positively or negatively affect oxidative status on the basis of training load, training specificity, and the basal level of training. In particular, the degree of oxidative damage and the time course for elevation in oxidative stress markers, during and following both acute aerobic and anaerobic exercise, resulted to be dependent on the type, intensity, volume, and duration of muscle contraction, leading to differences in the oxidative status between athletes in different sport disciplines [6, 8, 11–14].
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review
| 99.56 |
For a long time, endurance training was considered the main cause of oxidative stress, but it was clarified that free radicals can also be produced through other pathways, which are not necessarily related to the oxygen demand. Indeed, several studies have shown that even the anaerobic exercise (high intensity training, weight lifting, etc.) can produce similar levels of oxidative stress . Most of the studies regarding exercise-induced oxidative stress were carried out with exercise protocols including typical aerobic (running and cycling) and anaerobic (resistance training and sprints) exercise . Intermittent exercises such as sporting games (soccer, handball, water polo, basketball, etc.) involve both aerobic and anaerobic metabolism and have been received small attention in the literature. Water polo is an example of intermittent (“interval”) sport, requiring a high fraction of oxygen consumption, and is composed by high intensity bursts of sprinting, each lasting between 7 to 14 seconds, interspersed with short periods of low to moderate intensity swimming .
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| 99.9 |
Given the limited literature data available on oxidative stress response in water polo, we first investigated changes in oxidative stress biomarkers and antioxidant potential after a regular training program in a group of water polo male players. Moreover, we aimed to assess the effects of genetic background on oxidative response, with particular regard to the role played by single nucleotide polymorphisms (SNP) A16V of SOD2, encoding for intracellular Mn-SOD, −844 G>A of CAT, and rs1800668 of GPx-1.
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Twenty-eight Sicilian water polo male players participated in this study (age 25.1 ± 6.3 years; height 1.81 ± 0.07 m; body mass 85.5 ± 14.5 Kg; BMI 26.4 ± 4.4 Kg/m2; BSA 2.05 ± 0.16 m2). The players had at least 3 years of training and competition experience and took part in several competitions/year.
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All participants completed medical history and exercise as well as lifestyle questionnaires to assess their current levels of physical activity and nutritional status. The mean consumption of fruits and vegetables in the whole study cohort was around 1 portion/day.
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The recruited players followed a training routine of five days per week, with sessions lasting 4 h per day (2 h of swimming training and 2 h of water polo training, except Wednesday-match simulation). Indeed, the athletes trained five days per week, following a mesocycle preparation program. A mesocycle represents a phase of training with a duration of 2–6 weeks or microcycles, where the training program emphasizes the same type of physical adaptations, for example, muscle mass and anaerobic capacity. During the preparatory phase, a mesocycle commonly consists of 4–6 microcycles. The goal of the plan is to fit the mesocycles into the overall plan timeline-wise to make each mesocycle end on one of the phases and then to determine the workload and type of work of each cycle based on where in the overall plan the given mesocycle falls. The goal in mind is to make sure the body peaks for the high priority competitions by improving each cycle along the way.
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| 99.6 |
A blood sample of 4 mL was drawn from all participants 30 minutes prior to the match simulation, in a sitting position, from a forearm vein. A second blood sample was drawn 15 minutes after the simulated match (90 minutes of physical activity) from a forearm vein of the other arm. Several aliquots of whole blood, as well as plasma and serum fractions, obtained after centrifugation, were prepared and stored at −80°C until analysis.
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The athletes or their parents, when needed, were informed about the aims of the study, and both provided a written informed consent form authorizing the present investigations. All procedures were conducted in accordance with the principles outlined in the Declaration of Helsinki for all human investigations.
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The concentrations of advanced oxidation protein products (AOPP) were analyzed by a colorimetric assay, using Chloramine T as standard, as described by Alagozlu and coworkers . Reference limits for this method were <100 μmol/L according to values reported in the general Caucasian population .
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| 99.94 |
Superoxide dismutase (SOD) activity was assayed according to the method of Paoletti and Mocali . This assay is based on the oxidation of nicotinamide adenine dinucleotide reduced disodium salt mediated by a purely chemical reaction sequence which involves EDTA, Mn(II), mercaptoethanol, and molecular oxygen. The decrease of the rate of NADH oxidation is a function of enzyme concentration.
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| 99.94 |
The measurement of CAT activity was carried out by measuring the rate of H2O2 breakdown at 240 nm according to the method of Luck . Catalase activity was calculated based on the extinction coefficient of 43.1 M−1 cm−1 for H2O2 at 240 nm and expressed as nmoles of H2O2 consumed/min/mg of protein.
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| 100.0 |
Plasma levels of lactic dehydrogenase (LDH) activity, creatine kinase (CK) activity, creatine kinase-MB (CK-MB), myoglobin (MGB), and troponin, as markers of muscle damage, were assessed by Siemens autoanalyzers (ADVIA 1800 and Centaur XP Siemens, Healthcare Diagnostics, Germany) using the appropriate reagent kit of the same company (Siemens, Healthcare Diagnostics, Germany). Reference ranges for these markers were LDH 140–280 U/L; CK ≤ 170 U/L; CK-MB ≤ 6.5 ng/mL; myoglobin ≤ 90 ng/mL; troponin ≤ 40 ng/mL.
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| 99.94 |
Genotyping for the SNPs SOD2 A16V (rs4880), CAT −844 G>A (rs769214), and GPx1 rs1800668 C>T was carried out by real-time PCR allelic discrimination in a 7500 Fast Real-Time PCR instrument (Applied Biosystems, Foster City, California, USA), using Predesigned TaqMan SNP Genotyping Assays (Applied Biosystems; assay ID: C_1202883_20, C_850486_20, C_2548962_20). Reaction conditions and thermal profile were the same reported by Gugliandolo and coworkers .
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| 99.94 |
Pearson's correlation was applied to assess the existence of any significant interdependence between numerical parameters. Compliance of genotype distribution to the Hardy-Weinberg equilibrium was estimated by Fisher's exact test, based on a Web program (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl).
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| 99.94 |
To examine the effects of analyzed polymorphisms on continuous variables the one-way ANOVA followed by the Bonferroni post hoc analysis was performed. A p value ≤ 0.05 was considered statistically significant for all the analyses. Statistical analyses were performed using Statistic program v.7 for Window package.
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Plasma levels of redox markers, namely, dROMs, BAP, thiols, and AOPP, as well as enzyme activities of SOD, CAT, and GPX, were assessed in water polo players before and after exercise and are shown in Table 1. We observed that, in resting conditions, the mean levels of oxidated molecules (dROMs, AOPP) were increased, while antioxidant defenses (BAP, thiols) were reduced in comparison with normal reference ranges. This indicated a very high level of oxidative stress in water polo players recruited for this study. Postexercise mean plasma levels of dROMs, and those of BAP and total free thiols, were significantly higher and lower, respectively, than those before exercise. No significant changes after training were observed in mean plasma levels of AOPP as well as SOD, CAT, and GPx enzyme activities.
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| 100.0 |
We also assessed the variations between preexercise and postexercise values in plasma levels of muscle damage markers, such as LDH, CK, CK-MB, myoglobin, and troponin (Table 1). Notably, at rest mean plasma concentrations of LDH were higher than normal reference values, while CK, CK-MB, myoglobin, and troponin levels were found to fall in the normal reference range. However, the levels of all muscle damage markers, except troponin, were found to be significantly increased after exercise in comparison with those measured before exercise.
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The ratios between post- and preexercise values of redox markers were also calculated, and a correlation analysis was carried out to assess the relationships among the different markers. A significant positive correlation was found between the ratios of dROMs and those of AOPP (R = 0.44, p = 0.019), as well as dROMs and the muscle damage markers troponin (R = 0.587, p = 0.001) and myoglobin (R = 0.771, p = 0.000), and also between AOPP and LDH (R = 0.459, p = 0.014), SOD activity and LDH (R = 0.422, p = 0.025), CAT activity and CK (R = 0.473, p = 0.011), and LDH and CK (R = 0.409, p = 0.031). Instead, a significant negative correlation was observed between the ratios of dROMs and BAP (R = −0.48, p = 0.008), dROMs and thiols (R = −0.483, p = 0.009), and BAP and myoglobin (R = −0.644, p = 0.007).
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study
| 100.0 |
Genotyping of recruited subjects for the SOD2 A16V polymorphism showed that the two alleles had the same frequencies in water polo players (A 0.50 versus V 0.50). The heterozygous AV16 genotype was the most represented among athletes, being found in 57.2% (n = 16) of the study cohort, while AA wild-type (21.4%; n = 6) and VV homozygous mutated subjects (21.4%; n = 6) had the same distribution.
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study
| 100.0 |
A largely higher frequency was found for the CAT −844 G wild-type allele in comparison with the A mutated allele (0.79 versus 0.21). Notably, the −844 A mutated allele was only found in heterozygous state, with the GA heterozygous genotype being represented in 42.8% (n = 12) of the recruited subjects. The GG wild-type genotype was present in 57.2% (n = 16) of the study cohort.
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study
| 100.0 |
The analysis of GPx1 rs1800668 genotype distribution pointed out that the C wild-type allele had a higher prevalence than the T mutated allele among the recruited water polo players (0.54 versus 0.46). The CT heterozygous genotype was the most frequent, being present in 50% (n = 14) of the studied population. As a whole, people bearing the T mutated allele accounted for over 70% of recruited water polo players, being also present in homozygous state in 21.4% (n = 6) of the study cohort. Wild-type subjects represented 28.6% (n = 8) of the study subjects.
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| 100.0 |
In order to understand the effects of genetic background on the variability of redox markers levels water polo players were grouped according to their genotype, and a between-groups comparison was carried out to assess differences in the plasma concentrations of redox markers, in resting conditions and after training (Table 2).
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study
| 100.0 |
No significant differences were found among water polo players having different SOD2, CAT, and GPx1 genotype with regard to preexercise plasma levels of dROMs, BAP, and total thiols (Table 2). Moreover, AOPP plasma concentrations were not significantly different in individuals with different CAT and GPx1 genotype, while they were found to be significantly higher in water polo players having the SOD2 AV16 genotype than in those with VV genotype (Table 2). Notably, after 90 minutes of exercise AOPP concentrations were significantly increased not only in individuals bearing the SOD2 AV16 but also in those with VV16 genotype in comparison with those bearing the AA genotype (Table 2). After exercise, plasma values of dROMs were increased, while those of BAP and free thiols were concomitantly decreased, in water polo players having either heterozygous or homozygous mutated genotype for SOD2 V16A, CAT −844 G>A, and GPx1 rs1800668 polymorphisms compared with those having wild-type genotypes (Table 2). However, these differences were found to be significant only for subjects having either the CAT GA genotype or GPx1 CT genotype (Table 2), likely due to the small group size.
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study
| 100.0 |
We also examined the influence of gene polymorphisms on the extent of redox marker variations following exercise that were calculated as the ratios between post- and preexercise values. Significant differences were observed only when analyzing the impact of the GPx1 rs1800668 on AOPP and dROMs variations. In particular, growing AOPP concentration ratios were observed in GPx1 TT mutated homozygous water polo players compared with athletes having other genotypes, while a significant increase in dROM ratios was found in TT or CT subjects compared with wild-type athletes.
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study
| 100.0 |
Then, we analyzed the influence of different SOD2, CAT, and GPx1 genotypes on antioxidant enzyme activities (Table 3). In resting conditions significant differences were found only for water polo players having either the CAT −844 GA or GPx1 rs1800668 CT or TT genotype that exhibited greater SOD and GPx enzyme activities in comparison with wild-type athletes. Instead, all the examined polymorphisms did not affect CAT enzyme activity. Interestingly, the CAT-844 G>A genotype was also shown to be associated with a significant increase of postexercise GPX enzyme activity in comparison with wild-type CAT genotype GG, and the GPx1 rs1800668 CT genotype resulted to be associated with significantly increased postexercise CAT enzyme activity in comparison with wild-type GPx1 CC genotype. Surprisingly, the GPx1 rs1800668 TT genotype was associated with a significant reduction in postexercise GPx and CAT enzyme activities in comparison with wild-type GPx1 CC genotype. However, these results should be considered with caution given the small number of homozygous subjects that may be not representative of actual variations (Table 3).
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study
| 100.0 |
Finally, we analyzed the influence of different SOD2, CAT, and GPx1 genotypes on the variability of muscle damage markers (Table 4). In resting conditions significant differences were found only for water polo players having either the SOD AV16 genotype or the VV16 genotype that exhibited greater myoglobin or greater troponin, myoglobin, and CK-MB values, respectively, in comparison with wild-type athletes. Instead, the CAT −844 G>A and the GPx1 rs1800668 C>T did not affect plasma concentrations of muscle damage markers. After exercise we found that athletes with SOD2 AV16 genotype had higher LDH concentrations than those with AA or VV genotype, while athletes having the SOD VV16 genotype had significantly higher concentrations of CK and myoglobin in comparison with wild-type AA or heterozygous AV ones (Table 4).
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study
| 100.0 |
Several investigations provided evidence that exercise may positively or negatively affect oxidative status on the basis of training load, training specificity, and the basal level of training. In particular, the degree of oxidative damage and the time course for elevation in oxidative stress markers, during and following both acute aerobic and anaerobic exercise, result to be dependent on the type, intensity, volume, and duration of muscle contraction, and also on gender, age, individual fitness levels, and nutritional status, leading to differences in the oxidative status between athletes in different sport disciplines [4, 8, 12, 13].
|
review
| 98.9 |
A water polo match is characterized by high intensity intermittent activity with periods of intensive muscular activity followed by periods of moderate exercise or even rest, which involves both aerobic and anaerobic metabolism . In elite female water polo players it has been observed that the concentration of blood biomarkers of oxidative stress and inflammation varies over the course of an agonistic season . Our results demonstrated that, at rest, athletes exhibited dROM, BAP, and AOPP plasma levels, representing valuable markers of oxidative stress, outside of the desirable concentration ranges, indicating an imbalance between prooxidants and antioxidants. Interestingly, AOPP plasma concentrations were higher than those previously observed in a group of elite hurdlers , in agreement with the suggested influence of training level and mode on oxidative stress. The high level of oxidative stress found in resting athletes, recruited for this study, was likely a consequence of the high-volume training required during the mesocycle preparatory phase. In addition, after training we observed a further increase in dROM values and a reduction in total antioxidant capacity in comparison to rest values. Training session of team sports and/or match may also lead to an inflammatory response associated with muscle injury due to eccentric contraction used in these sports . Notably, intensified training was shown to induce a biphasic response of total antioxidant capacity, represented by a significant increase after low- and high-volume training, and a decline after very high-volume training . This condition, together with weekly competition and a diet at low intake of fruits and vegetables, impeded the normal recovery of athletes and may play a major role in the development of chronic oxidative stress and cellular damage .
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study
| 100.0 |
It has been hypothesized that SOD, CAT, and GPx, which represent the major enzymatic antioxidant systems involved in ROS scavenging, display different features of adaptation to training. Both CAT and GPx convert hydrogen peroxide (H2O2) produced by SOD to water and oxygen, but the threshold of H2O2 for their induction is different. During moderate exercise GPx activity is enough to scavenge low levels of produced H2O2, while after strenuous exercise there is an excessive production of H2O2 leading to an increase in CAT synthesis to compensate for the insufficient clearance of H2O2 by GPx .
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study
| 99.94 |
In our study, although we observed a reduction in BAP levels after training, the evaluation of SOD, CAT, and GPx activity did not reveal significant differences between pre- and postexercise values. This could be explained by the fact that the enzymatic antioxidants are mainly present intracellularly, while nonenzymatic antioxidants prevail at extracellular level. Indeed, it has been shown that, in condition of strenuous and continuous training, variations of antioxidant parameters are different. As example, erythrocyte SOD, GSH-Px activities, and blood GSH were shown to be unchanged, while plasma total antioxidant status was decreased, and plasma GSH-Px activity increase failed to prevent oxidative exercise-induced damage in overloaded triathletes . This suggests nonsynergistic responses in antioxidant parameters during OT (even if some parameters eventually adapt, it may be insufficient to prevent oxidative damage).
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study
| 100.0 |
We also analyzed levels of LDH, CK, and CK-MB that have been confirmed as useful serum markers of muscle injury. During exercise the increase in ROS production can induce lipid peroxidation which in turn alters membrane permeability causing the release of protein from myocells. Previous animal studies reported a positive correlation between increased lipid peroxidation and CK as well as aspartate-aminotransferase, suggesting that biomarkers of muscle damage during exercise are indicative of oxidative stress . Serum CK concentrations may change in response to eccentric exercise too. Water polo is considered a noneccentric exercise mode; nevertheless there is evidence of relevant cocontraction muscular intervention modes, possibly implying also eccentric actions of the antagonist muscle . An adaptive behavior of trained muscle depending on type and duration of exercise has been demonstrated. Peak values in serum CK have been recorded after endurance event as well as in eccentric exercise . Also markers of myocardial damage, such as the CK-MB isoenzyme, myoglobin, and cardiac troponins, are affected by prolonged or strenuous exercise . However, Dahlqvist et al. suggested that cardiac troponin represents a marker of more severe alterations associated with sarcomeric damage. Indeed, it has been demonstrated that cardiac troponins appear in blood of well-trained athletes competing in ultra-endurance events such as Ironman Triathlon or exercise of even longer duration, while they are not detected in blood after intermittent or short duration (<90 min) exercise [30, 31]. Accordingly, in water polo players after training we reported an increase in LDH, CK, CK-MB, and myoglobin plasma levels, while no changes were observed for troponin. These results indicate that intermittent high intensity activity in water polo athletes causes a moderate muscle injury.
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| 100.0 |
The muscle injury is dependent on oxidative stress as shown by the positive correlation found between increased dROMs as well as AOPP and increased troponin, myoglobin, and LDH, and also between increased SOD activity as well as CAT activity and increased LDH and CK. Instead, high levels of BAP result to be protective against muscle injury, as shown by the negative correlation found between BAP and myoglobin.
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study
| 99.94 |
It has been shown that the A16 variant allows a 30–40% more efficient targeting of MnSOD to the mitochondria than V16 and therefore is associated with high levels of mitochondrial concentration and activity . In this study we observed higher levels of oxidative stress before and after exercise in athletes bearing the mutated allele V16, either in heterozygosis or in homozygosis, than in wild-type subjects, as shown by increased dROMs and AOPP and decreased BAP and free thiols. However, the differences with wild-type subjects were found to be significant only for variations of AOPP plasma levels. Differences in SOD2 A16V genetic background did neither affect plasma SOD activity nor affect CAT or GPx activities. This could be explained taking into account the fact that SOD2 represents the primary level of antioxidant defense in cellular mitochondria. Instead, the SOD2 A16V polymorphism represents a risk factor for increased muscle injury in water polo players, since athletes bearing the homozygous mutated VV16 genotype exhibited higher values of LDH, CK, CK-MB, troponin, and myoglobin than wild-type AA and heterozygous AV subjects, even if these differences were not always significant likely due to the small size of genotype subgroups.
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study
| 100.0 |
The CAT G-844A polymorphism may influence CAT transcription by modulation of the transcriptional factor binding position, and it has been postulated that the A allele is associated with decreased CAT activity in comparison with the G allele . Thus, it is reasonable to hypothesize that individuals bearing this CAT polymorphism are more susceptible to oxidative stress as they possess lower levels of CAT protein than wild-type subjects. Given the lack of AA homozygous subjects in the investigated population we could not fully evaluate the effect of this polymorphism on oxidative stress response. However, our results show that heterozygous GA water polo players had higher levels of oxidative stress than wild-type subjects, even if significant differences were only found for dROMs levels after exercise, probably due to the small size of sampled subgroups. These results were also confirmed by the examination of antioxidant enzyme activities, since heterozygous subjects had a significantly higher GPx activity before exercise, and significantly higher GPx and SOD activities after exercise. However, differences in CAT G-844A genetic background among the recruited water polo players did not affect the variability of muscle damage markers before and after exercise.
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study
| 100.0 |
GPx activity represents the second line of enzymatic antioxidant defense, and Gpx1, one of six isoforms of GPx, is widely present in human cells and in vascular endothelium too . The GPx1 rs1800668 (C>T) polymorphism has been reported to affect GPx1 gene transcription rate and could reasonably play a role in increased individual susceptibility to oxidative stress. Water polo players having the T mutated allele had pre- and postexercise increased levels of prooxidant markers (dROMs, AOPP) and decreased levels of antioxidant markers (BAP, thiols), even if significant differences were only found for dROMS after exercise, likely due to the small size of genotype subgroups. Our preliminary results suggest that the GPx1 rs1800668 polymorphism plays a major role in modulating antioxidant enzyme activities, since both SOD and CAT activities were significantly increased in heterozygous CT water polo players compared with wild-type subjects. Instead, this GPx1 polymorphism seems to play a minor role in muscle damage given that although water polo players having the CT heterozygous genotype showed the highest levels of LDH, CK, and myoglobin after exercise, these differences were not statistically significant in comparison with wild-type subjects.
|
study
| 100.0 |
Due to relative small number of water polo players recruited, the results of our study should be considered preliminary; then further investigations are required, for example, in order to examine the combined effects of all three polymorphisms in different haplotypes.
|
study
| 96.06 |
Moreover, the data on pre- and postexercise variations of redox biochemical parameters need to be more carefully evaluated. In fact, a correct standardization on timing and way of blood samples collection should be developed. For example, assessing redox status at beginning and end of season could be useful to monitor the real variations in oxidative stress parameters and the possible overtraining status in water polo players.
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other
| 99.6 |
Gastroenteritis (GE) is defined as the inflammation of the mucosal lining of the stomach and intestines. It is a very common presentation to the Emergency Room (ER) (and Out-Patient Departments), and the majority of cases are infectious, though a specific organism is not usually identified. According to the World Health Organization (WHO), it is a leading cause of death worldwide.1
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other
| 99.7 |
Treatment is mainly supportive, with an emphasis on rehydration and correction of any electrolyte imbalances. Anti-motility drugs and anti-secretory agents may also be used. Antibiotics are not routinely indicated, and their role in management of acute gastroenteritis (AGE) is not well defined- this will be the focus of this review.
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review
| 99.9 |
Antimicrobials can cause multiple side effects, and their inappropriate use results in development of resistance in various pathogenic organisms. Curtailing unnecessary use may result in fewer complications (and thus better treatment) as well as decrease the incident of drug resistant bacterial infections. At least one local study shows misuse/overuse of antibiotics in Pakistan.2
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other
| 95.8 |
Infectious GE can be caused by any of multiple organisms3 including viruses, bacteria and amoebae. As viral infection has no specific/targeted treatment, it will not be further discussed. Generally, as the causative organism will not be identified in the patient presenting to the ER with AGE, classification on the basis of the pathogen is not useful for this review. Thus, this paper will differentiate patients on the basis of presentation.
|
review
| 99.9 |
This is defined as loose, watery stool (without blood, lipid, mucus, etc.) for less than 14 days without evidence of septicaemia. Acute diarrhoeal illness tends to be a self-limiting disease, so treatment is mainly supportive. Antimicrobial therapy is not routinely indicated for numerous reasons. Firstly, there is a lack of evidence that antibiotic treatment is of any significant benefit4-8, so risks associated with its prescription cannot usually be justified.
|
review
| 99.5 |
Furthermore, antibiotic administration is associated with multiple possible adverse effects, including development of Clostridium difficile associated colitis9-12 (C. difficile colitis), a disease with significant rates of morbidity and mortality. C. difficile colitis is more common with the cephalosporin and quinolone groups of antibiotics, as well as amoxicillin and clindamycin.
|
review
| 99.7 |
In cases of patients infected with E. coli strain O157:H7, there is evidence that antibiotics may precipitate development of haemolytic-uraemic syndrome (HUS), a clinical syndrome more common in children but increasingly recognized in adults, without conferring any reasonable benefit.13-16 At least one study in vitro showed that gentamycin may safely reduce the release of shiga toxin (Stx) from Shiga toxin producing E. coli, but evidence is lacking to recommend the use of this antibiotic in most cases.17 If antibiotics must be given, an animal study suggests that macrolides, such as azithromycin, may also be a safer option.18 However, despite the possibility of inclusion of antibiotics in the treatment regimen for E. coli in the future, current evidence favours the avoidance of their use wherever possible.
|
review
| 99.9 |
Finally, but no less importantly, curtailing the inappropriate use of antibiotics should prevent the development of antibiotic resistant strains. This is important at a time that multiple drug resistant strains are being frequently recognized. This is not to say that antibiotics should never be prescribed in diarrhoeal illness, however.
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other
| 99.94 |
Typhoid is another gastrointestinal (GI) infection that warrants antimicrobial therapy. Though it is classically described as causing constipation, it can present with diarrhoea in a significant percentage of patients, especially later in the disease course. Antibiotics in this case greatly alter the natural disease course and have greatly decreased the mortality caused by typhoid. C. difficile colitis, a possible complication of antibiotic use (as mentioned above) may require administration of metronidazole (oral/intravenous) or vancomycin (orally).22
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other
| 62.84 |
Certain other groups may also benefit from antibiotic therapy: the immunocompromised (HIV, immunosuppressive drugs, recent irradiation, those with diabetes mellitus), the elderly (>65 years old), those with prostheses, those with congenital heart diseases, etc. It should be noted that there is not much in the literature regarding these groups.
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other
| 99.9 |
This is diarrhoea with blood and/or mucus. Antimicrobials should be administered in most cases of dysentery (e.g. dysenteric shigellosis)23-34 though there are caveats here, too, such as in the case of Campylobacter or Enterohemorrhagic E. coli (EHEC) infection.
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other
| 99.94 |
This refers to diarrhoea that lasts longer than two weeks. While there is good evidence that antimicrobials are useful in management of this condition, a search should be made for non-infectious causes as well. In the ER, unless the patient appears toxic/septic, treatment should be supportive while necessary investigations are carried out, after which targeted treatment may be started, as antimicrobials would not be warranted in the myriad other conditions that can cause persistent diarrhoea (IBD, Irritable bowel syndrome, hyperthyroidism, drugs such as selective serotonin re-uptake inhibitors (SSRIs), etc.)
|
other
| 99.9 |
The reason for widespread use of short course antibiotics for management of this condition is that they have shown to modestly reduce the duration of symptoms by a few days36, though without much impact on disease severity. However, given that symptoms are typically mild and short lived in the first place and that risks of developing antibiotic associated diarrhoea (or other side effects, such as Stevens-Johnsons Syndrome) and causing development of antibiotic resistance strains are fairly high, routine use of antimicrobials in this scenario may not be justified and cannot be routinely recommended.37 Commonly used drugs in this case are ciprofloxacin or co-trimoxazole (SMX/TMP) (with ciprofloxacin apparently superior), but it is worth keeping in mind that the FDA has recently strengthened warnings on use of ciprofloxacin.38 Further, due to developing resistance of Campylobacter to fluoroquinolones in Southeast Asia, azithromycin has become the drug of choice.39
|
review
| 99.6 |
The World Gastroenterology Organisation recommends that antibiotics be considered for cases of TD with moderate to severe diarrhoea, or in cases presenting with fever and/or dysentery.35 Thus, antibiotic treatment should be limited to those with severe symptoms, or those that cannot afford to alter travel plans.
|
other
| 99.9 |
Antimicrobial selection depends on the suspected pathogen. For example, the drug of choice for cholera is tetracycline, though doxycycline, azithromycin, or ciprofloxacin may also be used. For typhoid, recommendations vary by geography (due to different resistance patterns). In Southeast Asia, for instance, the preferred drug is cefixime. For TD, in immunocompetent patients, the drug selected should at least cover Shigella spp., Salmonella spp., ETEC, and Campylobacter spp. Traditionally, ciprofloxacin and co-trimoxazole have been used, though there have been concerns recently over its side effects and development of resistance, respectively.
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other
| 99.8 |
If the history is suggestive of amoebic infection, the recommended treatment is metronidazole and diloxanide,23,40 though there is data that suggests that a single dose of longer acting agent (e.g. secnidazole) is as effective as a course of metronidazole.41-43
|
review
| 97.5 |
In patients with severe illness, dysentery, signs of systemic infection, or those from high-risk groups, consider whether benefits outweigh the risks. Use patient history to guide the decision. Note that moderate dehydration in itself is not an indication of disease severity-it may instead indicate inappropriate fluid intake.
|
other
| 99.94 |
When deemed necessary, initiate therapy with an oral antimicrobial preparation if possible (i.e. if patient is tolerating oral feed; and is not septic) rather than IV administration as there is some data to suggest that IV antibiotics pose a greater risk of development of pseudomembranous colitis than their oral counterparts.
|
other
| 99.9 |
Future studies should focus on further defining the role of antimicrobials in the various clinical scenarios, so that an evidence-based approach may be adopted towards prescription of an antibiotic, and so that they are given only where there is a clear benefit.
|
other
| 99.9 |
2D materials such as graphene, hexagonal boron nitride (h‐BN), VS2, Bi2S3, and GaSe have been widely studied, because of their great potential in the field of catalysis, microelectronics, ion storage, and optoelectronics.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 As one of the most significant members of 2D materials family, transition metal dichalcogenides (TMDs), such as MoS2, MoSe2, WS2, and WSe2, have attracted tremendous attention currently due to their outstanding electronic, optical, and mechanical properties.11, 12, 13, 14, 15, 16, 17, 18, 19 Monolayer MoSe2 is a sandwich structure consisting of one Mo atom and two Se atoms, and the different layers are interacted by van der Waals force.20, 21 Like MoS2, the properties of MoSe2 are also related with layer numbers; monolayer MoSe2 exhibits a direct bandgap of 1.6 eV, whereas it changes into indirect bandgap of 1.1 eV for bulk or multilayer MoSe2.22, 23 N‐type channel behavior with an average mobility of ≈50 cm2 V−1 s−1 has been investigated for field‐effect transistors (FETs) based on monolayer MoSe2,24 while for bulk MoSe2 the carrier mobility is ≈100 cm2 V−1 s−1.25 In comparison with MoS2, MoSe2 shows a stronger light absorption in the solar spectrum range.26 It has been proved that MoSe2 can absorb nearly 5%–10% of incident sunlight in a thickness less than 1 nm.26 Moreover, bandgap engineering on MoSe2 could be accomplished by forming ternary alloy of MoS2(1–x)Se2x.17, 27, 28 Owing to these appealing properties, many efforts have been devoted to exploit the applications of MoSe2 in diverse fields, including ion batteries, FETs, and photovoltaics, etc.29, 30, 31, 32, 33
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review
| 99.75 |
Photodetectors based on 2D materials have been intensively investigated in recent years.34, 35, 36, 37 They show great potential for broadband, high‐sensitivity, and flexible photodetection due to the large light absorption and ultrathin thickness.34, 38 Although the gapless band structure of graphene offers the capability of ultrawide band detection, the short lifetimes of the photogenerated carriers in graphene (in the ps range) hinder the improvement of photocurrent.36, 39, 40 In comparison to graphene, TMDs such as MoS2 and MoSe2 possess large bandgap and thus higher carrier lifetimes, making them as promising candidates for high‐sensitivity photodetectors.34, 41, 42 For a practical photodetector, fast response speed is particularly important for the applications such as imaging and optical communication. However, due to the difficulty in controllable doping, most of the TMDs‐based photodetectors have a lateral device structure of metal‐semiconductor‐metal (MSM) or phototransistor. The transit time of carriers between two contact electrodes limits the device response speed.34 Moreover, the mono‐/multilayer structure of the nanosheets makes them very susceptible to the surface contamination or molecule adsorption, which also degrades the respond speed due to the carrier trapping/detrapping process.
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study
| 98.6 |
To date, a few works have been reported for the photodetectors based on mono‐/multilayer MoSe2 nanosheets.43, 44, 45 Although they show outstanding device characteristics such as remarkable light response, their response speed (15 ms–8 s) remains too low to meet the requirements for practical applications, and broadband light detection is yet to be demonstrated.43, 44, 45 In conventional photodetectors, diode structure with vertical p–n junctions are normally adopted. Therefore response speed could be greatly enhanced due to the presence of strong built‐in electric field at junction interface as well as the shorter carrier transit time.46, 47, 48 In light of this, fabrication of MoSe2 homo‐/heterojunction‐based photodetectors is much desirable to further boost their performance. For instance, Duan et al. demonstrated the lateral epitaxial growth of MoSe2/MoS2 heterojunctions, which showed pronounced photoresponse characteristics.49 Choi et al. also reported the construction of MoSe2/graphene van der Waals heterostructures, and investigated the rapid transfer of photogenerated charge carriers between MoSe2 and graphene.50
|
review
| 81.5 |
Herein, we demonstrated the fabrication of MoSe2/Si heterojunctions for high‐speed, broadband response photodetectors. High‐quality p‐n heterojunctions were formed by combing the p‐type Si substrate with n‐type MoSe2 film, thus bypassing the difficulty in controllable doping of MoSe2. More importantly, the MoSe2 film possessed a unique vertically standing layered structure, enabling the fast separation and transport of photogenerated carriers. Graphene (Gr) transparent electrode was adopted to further enhance the carrier collection and consequently reduce the recombination at junction interface. Significantly, the Gr/MoSe2/Si heterojunction photodetector exhibited a wide photoresponse range of 350–1310 nm and an extremely fast response speed of ≈270 ns, which represent the best values reported thus far for MoSe2 or MoS2 based photodetectors (Table 1 ).43, 44, 45, 51, 52, 53, 54 It is expected that the MoSe2/Si heterojunctions will have important applications for high‐performance optoelectronic devices.
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study
| 100.0 |
In this study, MoSe2 films with vertically standing layered structure were prepared by magnetron sputtering method with a thickness of ≈200 nm (see Figure S1 in the Supporting Information). The scalable sputtering method ensures the large‐area fabrication of high‐quality MoSe2 films with high uniformity, in contrast to the small size MoSe2 nanosheets obtained by exfoliation or thermal evaporation methods.55, 56 The as‐prepared MoSe2 film has trigonal phase (see Figure S2 in the Supporting Information). After deposition, the film was annealed in a rapid thermal processing systerm (RTP) at 800 °C in Ar for 20 min to further improve its crystal quality. Figure 1 a depicts the Raman spectra of the MoSe2 films of both as‐prepared and annealed MoSe2 films. Two typical Raman active modes, A1g and E2g, for MoSe2 are observed. The prominent A1g mode relates to the out‐of‐plane vibration of Se atoms, while the E2g mode is associated with the in‐plane vibration of Mo and Se atoms (see the inset in Figure 1a). Prior research results indicate that the change in layer number of MoSe2 nanosheets will cause a significant difference in the locations of scattering modes in Raman spectra; the E2g vibration will redshift, whereas the A1g vibration will blueshift, with increasing MoSe2 layer number.20, 57 Considering the large thickness of the MoSe2 film in this work, its Raman spectra are more likely to be identical to that of the MoSe2 bulk material or multilayer nanosheets. From Figure 1a, A1g and E2g scattering modes located at wave numbers of 240.3 and 288.1 cm−1, respectively, can be identified for the annealed film, which is consistent with previous reports for MoSe2 film.58, 59 It is reported that the obvious E2g peak usually occurs for monolayer MoSe2 nanosheet, whereas a thick MoSe2 film (≥2 layers) often exhibits a weak or invisible E2g peak.59, 60 Presumably, the unusually high E2g peak for the sputtering fabricated MoSe2 film may be attributed to the unique vertically standing layered structure.61 Figure 1b reveals an obvious movement of A1g peak from 235.2 cm−1 before annealing to 240.3 cm−1 after annealing, along with the decrease of peak width upon annealing. It is known that the A1g peak location of 240.3 cm−1 is more close to the standard value for high‐quality MoSe2 (240.6 cm−1).58, 59 Therefore, the Raman spectra clearly show that the film quality is significantly improved after annealing treatment. The components of the annealed MoSe2 film were further studied by X‐ray photoemission spectroscopy (XPS), as shown in Figure 1c,d. The Mo 3d shows two peaks at 229.2 and 232.3 eV, which can be attributed to the Mo 3d5/2 and Mo 3d3/2, respectively, confirming the existence of Mo4+.58, 62, 63 The peaks at 54.8 and 55.6 eV are attributed to the doublet Se 3d5/2 and Se 3d3/2, respectively, corresponding to the divalent selenide ions (Se2−).58, 62, 63
|
study
| 100.0 |
a) Raman spectra of both as‐prepared and annealed MoSe2 films. Schematic illustrations in (a) depict the atomic vibration direction of A1g (left) and E2g (right) Raman modes of MoSe2 film. b) Comparison of the A1g peaks in Raman spectra for the as‐prepared and annealed MoSe2 films. XPS spectra show the binding energies of c) Mo and d) Se for the annealed MoSe2 film.
|
study
| 100.0 |
Figure 2 a illustrates the device structure of MoSe2/Si heterojunction photodetector. MoSe2 film was first deposited on p‐type Si substrate with a predefined SiO2 circular window (d = 3 mm) by magnetron sputtering, which determines the effective device area. Ag electrode (50 nm) was deposited around the window as the top ohmic contact to MoSe2 film (see Figure S3 in the Supporting Information). Then three‐layer graphene film with sheet resistance of ≈380 Ω sq–1 (conductivity ≈7740 S/cm) was transferred to the top of MoSe2 film as transparent electrode. The use of graphene electrode ensures the efficient light absorption of MoSe2/Si heterojunction, meanwhile facilitates the transport of photogenerated carriers from MoSe2 film to the Ag top electrode. Afterward, Au electrode (50 nm) was deposited at the rear side of p‐type Si as back ohmic contact. To gain more insight into the structure of the MoSe2/Si heterojunction, cross‐sectional transmission electron microscopy (TEM) investigation was performed, as shown in Figure 2b‐e. The MoSe2 film deposited by sputtering has a uniform thickness of ≈200 nm (Figure 2b). EDS elemental mappings on Si, Mo, and Se at the red square area in Figure 2b prove the formation of MoSe2/Si heterojunction. The uniform colour contrast for Mo and Se elements is an evidence of the high uniformity of the MoSe2 film. The energy dispersive X‐ray spectroscopy (EDS) line‐scanning analysis, Figure 2c, further confirms the compositions of MoSe2/Si heterojunction. From the high‐resolution TEM (HRTEM) image at the junction interface (Figure 2d), we can see that there is a thin interfacial oxide layer (≈5 nm) formed between the Si substrate and the MoSe2 film. Close investigation on the MoSe2 film, Figure 2e, discloses the distinct vertically standing layered structure of the film, i.e., the growth direction of the (001) molecule planes of MoSe2 are perpendicular to the Si substrate, in contrast the parallel growth of the MoSe2 nanosheets fabricated by conventional chemical vapour deposition (CVD) method.57, 64 The dimension of individual crystal grains in the MoSe2 film is 4–6 nm wide, corresponding to about 6–9 MoSe2 monolayers (Figure 2e). As one of the remarkable characteristics of 2D materials, they show pronounced anisotropic conduction in the in‐plane direction and out‐of‐plane direction. The weak van der Waals force and the large layer distance between adjacent layers lead to much lower out‐of‐plane electrical and thermal conductivities compared to those of their in‐plane analogs.65, 66 In this regards, the vertically standing layered structure endows the MoSe2 film distinct electrical properties with much efficient carrier transport from the junction interface to the top electrode.
|
study
| 100.0 |
a) Schematic illustration of the Gr/MoSe2/Si heterojunction photodetector with graphene transparent electrode. b) Cross‐sectional TEM image of the interface of MoSe2 and Si. Insets show the EDS element mappings of Si, Mo, and Se at the red square area. c) The line‐scan EDS analysis along the red line from Si to MoSe2 film in (b). d) HRTEM image of the heterojunction, indicating the existence of an interfacial oxide layer (≈5 nm). e) HRTEM image of the MoSe2 film, verifying the vertically standing layered structure of the film. Inset shows the enlarged HRTEM image. The distance between two layers is ≈0.62 nm, corresponding to the (001) face of MoSe2.
|
study
| 100.0 |
Figure 3 a,b depicts the current versus voltage (I–V) characteristics of the MoSe2/Si heterojunctions in the dark and under light illumination, respectively. Both of the devices with and without graphene transparent electrode were measured to ascertain the role of graphene in determining the device performance. From the dark I–V curves, we note that the dark current at reverse bias direction (−5 V) decreases from 9.35 μA to 2.82 μA, whereas the dark current at forward bias direction (+5 V) increases from 2.6 mA to14.9 mA, after the use of three‐layer graphene transparent electrode. Correspondingly, the rectification ratio improves significantly from 278 for the device without graphene to 5284 for the device with graphene within ±5 V. As a result of the improved diode characteristic, under white light illumination (23 mW cm−2), the photocurrent at −5 V increases remarkably from 202 μA to 263 μA after the use of graphene transparent electrode. Figure 3b depicts the magnified I–V curves around the zero point under light illumination, revealing an open circuit voltage (V oc) of 100 mV for the device with graphene electrode, in contrast to the much lower V oc of 40 mV for the device counterpart without graphene electrode. Ideality factor (n) of the MoSe2/Si heterojunctions were deduced from the slops of the semilog I–V curves at the forward bias direction (Figure 3c), according to the following equation67 (1)n =qkBT dVdln Iwhere q is the unit charge, k B is the Boltzmann's constant, and T is the absolute temperature. The ideality factor of the MoSe2/Si heterojunction without graphene electrode exhibits a larger value of 2.43, compared to that of 1.79 for the device with graphene electrode. The above results collectively demonstrate that the graphene electrode plays a crucial role in enhancing the device performance of MoSe2/Si heterojunction. To understand the superior performance of MoSe2/Si heterojunction with graphene transparent electrode, Figure 3d,e illustrates the energy band alignments of the MoSe2/Si heterojunctions without and with graphene electrode, respectively. The n‐type MoSe2 film will form type II heterojunction with p‐type Si substrate, allowing the efficient separation of photogenerated electron‐hole pairs at junction interface. Under light illumination, electrons inject into the n‐type MoSe2 film, while holes inject into p‐type Si, forming the photocurrent. Notably, the introduction of graphene at MoSe2 side can greatly enhance the separation of photogenerated carriers. Moreover, the high conductivity of graphene can ensure the fast transport of electrons to the outside electrical circuit. As a result, the accumulation of electrons in MoSe2 film is avoided. This further reduces the electron–hole recombination and contributes to the improved photocurrent of the MoSe2/Si device. The zero bias barrier of the heterojunction, Φ b, was calculated based on following equation68 (2)I =IS [exp(eVnkBT)−1]
|
study
| 100.0 |
a) Typical I–V curves of the MoSe2/Si heterojunction with and without graphene transparent electrode measured in dark and under white light illumination (23 mW cm−2), respectively. b) Magnified I–V curves around zero point under light illumination. c) Semilogarithmic I–V curve at forward bias of 0–0.4 V in the dark. The semilogarithmic curves could be fitted by straight lines. Energy band alignments of the MoSe2/Si heterojunctions d) without graphene and e) with graphene transparent electrode. The conduction band minimum (CBM) and the valence band maximum (VBM) of Si and MoSe2 are represented in blue colour and brown colour, respectively. The work function of graphene (4.5 eV) is also shown in black line. The energy scale is referenced to the vacuum level.
|
study
| 100.0 |
The saturation current of I S is defined by (3) IS= AA*T2exp(−qΦbkBT)where A is the area of the device (7.06 mm2), A* is the effective Richadson constant, and it is 32 A cm−2 K−2 for p‐type Si.69 Based on above equations, Φ b is deduced to be 793 mV for the heterojunction device with graphene top electrode. The large bulit‐in electrical field is responsble for the effective spearation of photogenerated carriers.
|
study
| 99.94 |
To evaluate the performance of the Gr/MoSe2/Si heterojunction for broadband detection, UV light (365 nm), green light (500 nm), and red light (650 nm) were chosen as exciting light sources. From I–V curves of the device measured at different light wavelengths (Figure 4 a), it is observed that the device shows a remarkable photocurrent upon incident light illumination at reverse bias. The high sensitivity at reverse bias is due to the fact that the photogenerated electron‐hole pairs significantly change the concentration of minority carriers, which dominates the photocurrent under a reverse bias.70 From the time‐dependent photocurrent excited by pulsed UV light (365 nm, 15 mW cm−2) at different reverse bias voltages, Figure 4b, we note that the device exhibits a high sensitivity to the UV light with a large I on/I off ratio of 140 and 130 at −1 V and −2 V, respectively. The fast response and recovery speed can be deduced by the steep rise and fall edges of the response curves, indicating the effective generation and separation of electron–hole pairs in the Gr/MoSe2/Si heterojunction. In addition, excellent stability and reproducibility can also be verified by the unchanged response current of the device illuminated with a pulsed light with about 16 s per cycle. To quantify the performance of the Gr/MoSe2/Si photodetector, two key figure‐of‐merit parameters, i.e., responsivity (R) and detectivity (D*) that indicate the efficiency of a detector responding to optical signals and the ability of a detector to detect weak optical signals, respectively, are calculated by following equations71 (4)R =IphPin (5) D*=A1/2R(2qId)1/2 =R(2qJd)1/2where I ph, P in, I d, and J d represent the photocurrent, incident light power, dark current, and dark current density, respectively. Figure 4c plots both the responsivity and detectivity at different light wavelengths as a function of applied reverse bias voltage. It is seen that the responsivity at different wavelengths increases, whereas the detectivity first increases and then decreases, with increasing reverse bias voltage. The higher reverse bias can result in a larger photocurrent under the same incident light intensity since more carriers can pass through the junction, thereby contributing to an increased responsivity. However, the dark current will increase at the meantime, ultimately resulting in the decrease of detectivity at high reverse bias. Based on Equations (4) and (5), the Gr/MoSe2/Si photodetector shows optimal R and D* values of 270 mA W−1 and 7.13 × 1010 Jones (Jones = cm Hz1/2 W−1) at 650 nm, 93 mA W−1 and 2.55 × 1010 Jones at 500 nm, and 182 mA W−1 and 6.22 × 1010 Jones at 365 nm, respectively. Figure 4d depicts the absorption spectrum of the MoSe2/Si heterojunction, with the spectra of both of MoSe2 film on quartz substrate and bare Si substrate for comparison. The MoSe2 film possesses stronger light absorption at both short wavelength direction (<800 nm) and long wavelength direction (>1060 nm) as compared to the bare Si substrate. Therefore, the combination of MoSe2 film with Si substrate makes the system capable of absorption of the broadband light ranging from UV, visible, to NIR light. In addition, it is noted that there is an absorption valley around 500 nm. This may be responsible for the relatively lower responsivity and detectivity at that wavelength.
|
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| 100.0 |
a) I–V characteristics of the Gr/MoSe2/Si photodetector measured in the dark and under light illumination with varied wavelengths of 365, 500, and 650 nm, respectively. Three‐layer graphene was used as the transparent electrode. The light intensities of the light sources were fixed at 15 mW cm−2. b) Time‐dependent photocurrent excited by pulsed light at 365 nm (15 mW cm−2). Different bias voltages of −1 V and −2 V were applied. c) Plots of responsivity and detectivity of the device at varied light wavelengths as a function of applied reverse bias. d) Absorption spectrum of the MoSe2 film on Si substrate. The absorption spectra of MoSe2 film grown on quartz substrate under the same conditions and bare Si substrate were also plotted for comparison. e) I–V characteristics of the device measured in the dark and under laser illumination with different wavelengths of 808, 1064, and 1310 nm, respectively. The light intensity was maintained at 15 mW cm−2. f) Photoswitching curves of the device in response to pulsed light illumination with various wavelengths at a bias voltage of 0 V.
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The NIR photoresponse of the Gr/MoSe2/Si device was further assessed by using the 808, 1064, and 1310 nm lasers as light sources. In Figure 4e, the device exhibits remarkable photoresponse to 808 and 1064 nm lasers. However, photoresponse becomes weaker for the 1310 nm laser since its energy (0.95 eV) is already smaller than the bandgap of MoSe2 film (1.1 eV). Significantly, owing to the pronounced photovoltaic behavior, the device can operate at zero bias voltage with excellent reproducibility and stability (Figure 4f). The step rise and fall edges to pulsed light also reveal that the photocurrent and photo‐induced voltage are originated from photovoltaic effect, instead of bolometric effect.
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Fast response of a photodetector is requisite for many advanced applications such as optical communication, biological sensing, missile tracking, and so on. In this work, we further investigated response speed of the Gr/MoSe2/Si heterojunction photodetector by using an oscilloscope to monitor variation of photovoltage under pulsed red light illumination (Figure 5 a). The pulsed red light (650 nm) was produced from a laser diode (LD) supplied by a tuneable square‐wave signal generator at 14 V. Figure 5b,c and Figure S4 in the Supporting Information show the photoresponse of the Gr/MoSe2/Si photodetector to pulsed light with frequency ranging from 1 kHz to 1 MHz, manifesting that the device can work well even for high frequency (MHz) optical signals. In addition, from the enlarged photoresponse curve at 1 MHz, Figure 5d, rise time (t r) and fall time (t f) are estimated to be 270 and 350 ns, respectively. The response time of the LD light source is ≈6 ns (Figure 5d), ensuring the accurate evaluation of the device response time. It is noteworthy that this response speed is much quicker than the current reports on MoSe2‐based photodetectors, and even faster than other MoS2‐ or graphene‐based photodetectors (Table 1). This ultrafast response speed can be attributed to the unique device structure of the Gr/MoSe2/Si photodetector: (i) Unlike the conventional photoconductors or phototransistors with MSM structures, whose response speed is usually limited by the transmit time of the carriers between two contacts and the defects/traps in the conduction channels, strong built‐in electric field in the Gr/MoSe2/Si heterojunction photodetector can greatly facilitate the separation and transport of photogenerated carriers. (ii) The distinct vertically standing layered structure of MoSe2 film ensures the fast transport of photogenerated carriers along the vertical direction due to the high in‐plane mobility. The transmit time should be less than 1 ns from the junction interface to the top electrode by assuming a mobility of 100 cm2 V−1 s−1 and a layer thickness of 200 nm for the MoSe2 layer. (iii) The use graphene transparent electrode can further enhance the carrier collection and thus reduce the carrier recombination. This is also evidenced by Figure 5e, in which the temporal responses of both the devices with and without graphene electrodes were measured. The former exhibits much faster light response than the latter. Furthermore, we studied the relative balance (Vmax–Vmin)/Vmax as a function of pulsed light frequency (Figure 5f). It is noteworthy that relative balance of the Gr/MoSe2/Si heterojunction photodetector decreases by less than 15% even at 10 kHz and remains more than 10% at 1 MHz. In contrast, relative balance of the device without graphene transparent electrode diminishes sharply and approximates to zero at 10 kHz.
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a) Schematic illustration shows the rapid separation and transport of electrons and holes along the in‐plane direction of MoSe2 under pulsed light illumination. The electrons were collected by graphene transparent electrode, ensuring the fast transport of electrons to the outside electrical circuit. Variation of photovoltage is monitored by an oscilloscope to determine the response speed. Photoresponse of the self‐powered photodetector to pulsed light illumination with varied frequency of b) 1 kHz, and c) 1 MHz. d) Enlarged photoresponse curve at 1 MHz. Rise time (t r) and fall time (t f) are the time intervals between 10% and 90% of peak response. Response curve of the 650 nm LD light source is also shown in the upper part of the figure for comparison. e) Photoresponse of the MoSe2/Si heterojunction with and without graphene transparent electrode under pulsed light illumination. f) Relative balance (V max–V min)/V max versus switching frequency of the devices with and without graphene.
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To gain insight into the mechanism of graphene top electrode for carrier collection, device simulation was conducted on the MoSe2/Si heterojunction by using a 2D semiconductor simulation package (ISE‐TCAD). Figure 6 a shows the simulated total current density distribution of the device with graphene top electrode at a forward bias of +1 V. The current distributes uniformly with high current density in the MoSe2 layer with the use of graphene electrode. In contrast, if only side part of the MoSe2 layer contacts with Ag electrode, corresponding to the case without graphene top electrode, the current distribution is very inhomogeneous (Figure 6b); only the region closes to the electrode shows higher current density, while the region (I section) away from the electrode has very low current density, indicating the poor carrier collection capability for the device. This result further confirms the important role of graphene transparent electrode in enhancing the device performance.
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In summary, high‐performance Gr/MoSe2/Si heterojunction photodetectors were constructed by depositing MoSe2 film with vertically standing layered structure on Si substrate. The heterojunction photodetectors can surpass conventional mono‐/multilayer structured MoSe2 photodetectors in terms of high light sensitivity (due to stronger light absorption of the thick film) and ultrafast response speed (due to presence of strong built‐in electric field and short transmit time). The high in‐plane mobility of MoSe2 ensures the fast separation and transport of photogenerated carriers from the junction interface to top electrode in the vertically aligned MoSe2 film. Moreover, three‐layer graphene was used as transparent electrode to further enhance the carrier collection and thus reduce the recombination at junction interface. As a result, the Gr/MoSe2/Si heterojunction photodetectors exhibited outstanding device characteristics with a wide response spectrum range of 365–1310 nm and an ultrafast response speed of ≈270 ns, which represent the best results achieved for MoSe2‐based photodetectors thus far. This work unveils the great potential of MoSe2/Si heterojunction for high‐performance optoelectronic devices.
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Growth of MoSe2 Film and Graphene: MoSe2 films were deposited on the Si substrate by RF magnetron sputtering (Kurt J Lesker, PVD 75) using a 2 in. MoSe2 target (ZhongNuo Advanced Material (Beijing) Company). The RF power was kept at 50 W with a direct current (DC) bias voltage of 225 V. The pressure in the chamber was 3 mTorr during deposition, and the substrate temperature was controlled to be 400 °C. To increase the quality of MoSe2 film, the as‐prepared MoSe2 films were annealed in a rapid thermal process system (RTP‐500V) at 800 °C for 30 min. Graphene used here was synthesized by CVD method using a mixed gas of H2 (3 sccm) and CH4 (50 sccm) as gas source at 1000 °C, and a 25 μm thick copper foil was used as the catalyst substrate.
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Fabrication of Devices: To fabricated the Gr/MoSe2/Si heterojunction photodetectors, a circular photoresist window (d = 3 mm) was first defined on the SiO2 (300 nm)/p‐type (100) Si (resistivity 1–10 Ω cm−1) substrate by photolithography (SUSS, MicroTec‐MJB4), followed by 5% HF etching for 300 s to remove the SiO2 in the window. After removing the residual photoresist by acetone, 200 nm MoSe2 film was deposited onto the window by sputtering. Afterwards, 50 nm Ag were deposited by e‐beam evaporation (Kurt J Lesker, PVD 75) around the circular window on the MoSe2 film using a shadow mask. Three‐layer graphene film was transferred onto the top of the MoSe2 film as transparent electrode. 50 nm Au was deposited by e‐beam evaporation onto the rear side of SiO2/Si substrate as ohmic contact to Si.
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Material and Device Characterizations: The thickness and crystal structures of MoSe2 film were determined by atomic force microscopy (AFM, Veeco) and X‐ray diffraction (XRD, PANalytical Empyrean), respectively. Raman spectra of the MoSe2 film were measured in a LabRAMHR800 Raman microscopy system using 514 nm laser as excitation source. XPS measurements were performed using a monochromatic Al Kα source (1486.6 eV) produced by the XPS system (Kratos AXIS UltraDLD). The XPS data were calibrated by comparing with C 1s peak to assure the correction. The absorption spectra of MoSe2 on quartz glass, Si substrate, and MoSe2/Si heterojunction were detected by UV–vis spectrometer (Perkin‐Elmer LAMBDA 750) equipped with an integrating sphere. To observe the interfacial structure of heterojunction, the cross‐section structure, element mapping, and line‐scan EDX were characterized by HRTEM (FEI Tecnai G2). The photoresponse of the photodetectors was detected using a semiconductor parameter analyzer (Keithley 4200‐SCS). The light sources were produced by a Xe lamp (CEL‐HXF300) with tunable output power and a monochromator (Zolix Instruments, Omni‐nx I). To measure the NIR photoresponse, 808, 1064, and 1310 nm lasers were also used as light sources (Changchun Laser Optoelectronics Technology, MW‐GX‐808, MW‐GX‐1064, and MW‐GX‐1310). Light intensity is measured by an optical power meter (CEL‐NP2000). The response speed of the photodetector was measured by using a LD (650 nm) driven by a function signal generator (Shengpu, F‐40), and a digital oscilloscope (Tektronix TDS 2012C) was used to monitor the variation of photovoltage.
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As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
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Mexico’s regulatory framework addresses the cultivation of genetically modified (GM) crops (Gutiérrez 2010). This framework consists of a Biosafety Law and an additional Bylaw published in 2005 and 2008, respectively (DOF 2005, 2008). The Biosafety Law requires stepwise field evaluations of GM crops, starting with small plots in an Experimental Phase followed by larger plots in a Pilot Phase prior to commercial plantings. Plant characterization data generated during the Experimental Phase allow Mexican regulators to assess for unintended effects and the absence of adverse impact of the GM crop on the receiving environment and plant health. Subsequently, these data facilitate the issuance of planting permits, thus advancing the regulatory process.
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