Participants were the parents and teachers of these children who were 5–8 years old (M = 6.32). They completed the Sensory Processing Measure (SPM) to evaluate the sensory profile, praxis and SOC of the children in both the home and classroom contexts. In the home context, the most affected was the ASD+ADHD group. The ADHD group obtained higher scores than the ASD group on the Body Awareness (BOD) subscale, indicating a higher level of dysfunction. The ASD group, however, did not obtain higher scores than the ADHD group on any subscale. In the classroom context, the most affected were the two ASD groups: the ASD+ADHD group obtained higher scores than the ADHD group on the Hearing (HEA) and Social Participation (SOC) subscales, and the ASD group obtained higher scores than the ADHD group on the SOC subscale. Regarding sensory modalities, difficulties in proprioception seem to be more characteristic to the ADHD condition. As for higher-level functioning, social difficulties seem to be more characteristic to the ASD condition. Differences between the two contexts were only found in the ASD group, which could be related to contextual hyperselectivity, an inherent autistic feature. Despite possible individual differences, specific intervention programs should be developed to improve the sensory challenges faced by children with different diagnoses.Children with neurodevelopmental disorders often show impairments in sensory processing (SP) and higher functions. The main objective of this study was to compare SP, praxis and social participation (SOC) in four groups of children: ASD Group ( Recent research has reported that a high percentage of children with different neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) show unusual responses to sensory experiences, compared to the responses offered by typically developing children with the same chronological age  Sensory modulation disorders, which affect the regulation of the level or intensity of the response that occurs in the presence of the sensory information, thus differentiating between over-responsiveness, under-responsiveness and sensory seeking, (2) Sensory discrimination disorders, which affect the ability to distinguish and identify sensory inputs, and (3) Sensorimotor integration disorders, which involve a difficulty in transforming sensations into motor responses, including postural disorders with a sensory basis and developmental dyspraxia, in which ideation and motor planning are compromised, producing difficulties in learning new motor tasks.Thus, because sensory information forms the building blocks for higher-order cognitive functions  to compare the characteristics of SP, praxis, and SOC of the four groups in the home context (information reported by parents); (2) to compare the same characteristics of the four groups in the classroom (information reported by teachers); and, (3) to compare –in each group separately- the characteristics reported by parents to those reported by teachers.Based on results from previous studies, we hypothesize that the three groups of children with neurodevelopmental disorders will obtain higher levels of dysfunction than the Comparison Group (CG) in both contexts. Additionally, we expect the ASD+ADHD Group to be the most affected, so that the profiles of this comorbid group and the CG are expected to be the most different.As for specific sensory patterns in each disorder, it is expected that the most affected sensory modalities in children with ASD would be hearing and touch, whereas in children with ADHD it is expected that the most affected modalities would be body awareness (BOD) and balance and motion, as well as vision and touch. Regarding the higher functions in each disorder, it is also expected that praxis would be equally affected in both disorders, but SOC would be more affected in children with ASD because the presence of social difficulties is a hallmark of ASD.As for the comparison among the three groups with neurodevelopmental disorders, we expect an additive effect in the comorbid group that would lead to obtain higher levels of dysfunction than in the other two groups with neurodevelopmental disorders.When comparing contexts, we hypothesize that the three groups of children with neurodevelopmental disorders will obtain higher levels of dysfunction in the classroom context than in the home context, considering the greater demands of school assignments, and teachers' opportunities to compare children's functioning with that of their peers, as well as certain environmental factors characteristic of the classroom context, such as stimulation overload produced by excessive noise, and unpredictable physical contact when working cooperatively , the ADHD Group (n = 21), the ASD+ADHD Group (n = 21), and the CG (n = 27).The participants in this study were the parents and teachers of a total of 90 children between 5 and 8 years old, who were divided into four groups: The ASD Group  methodology was used. These are special classrooms integrated in regular state schools in Valencia (Spain), where students with disorders affecting language and communication are enrolled. In these classrooms there are a maximum of 8 children attended by three specialists: a special education teacher, a hearing and language teacher and an educator. These children are not all the time in these special classrooms, but they share their timetable both in these classrooms and in their corresponding mainstream classroom, where they are usually accompanied by one of the specialists who work in the special classrooms. Children from the ADHD Group and the CG, however, were attending the same schools as the children in the ASD and ASD+ADHD Groups, but in the regular modality.SD = 1.11), and the mean non-verbal IQ measured by Raven's Colored Progressive Matrices Test . No statistically significant differences were found among the four groups of children on gender , non-verbal IQ , or chronological age . Table Table t Raven,  was 98.7SD = 4.52; range: 25–50). No statistically significant differences were found among the four groups of parents on gender  or age . The educational level of the parents was similar in the four groups, and the mean number of children in the family was about 1.80.Regarding families, around 80% of the participants in each group were mothers. The mean age of the parents was 39.23 . The age range of the teachers was from 26 to 60, with statistically significant differences in age between the two groups , as the teachers of the ASD and ASD+ADHD Groups were younger than the teachers of the ADHD and CGs. Regarding educational level, the teachers in the ASD and ASD+ADHD Groups had more academic training than the teachers in the other groups, and this difference was statistically significant . All the teachers had between 5 and 36 academic years of teaching experience, with teachers in the ADHD and CGs having more experience than the teachers in the other groups . Teachers in the ASD and ASD+ADHD Groups had also more academic years of contact with their students than teachers in the ADHD and CGs .A total of 35 teachers participated in the study, of whom 18 were Therapeutic Education or Hearing and Language Teachers in the TEACCH classrooms who completed the questionnaires about the children in the ASD and ASD+ADHD Groups, and 17 were the mainstream classroom teachers who completed the questionnaires about the children in the Comparison and ADHD Groups. Most of the teachers were females, with the exception of two males, but no statistically significant gender differences were found between the two groups of teachers  questionnaires. Parents from the ASD and ASD+ADHD Groups also provided information about autism severity by answering the questions on the GARS-2 , with higher scores indicating a greater degree of autism, so that three categories are established: Improbable Autism (AI score below 70), Possible Autism (AI score from 70 to 84), or Probable Autism . The GARS-2 is a widely-used tool to assess ASD symptoms, and it has been adapted and validated in different countries, with results showing good psychometric characteristics. For the Spanish version, the scale's internal consistency was high , and the scale's criterion validity with the Autism Behavior Checklist was also high (0.94).This screening scale provides a norm-referenced measure that helps to identify autism and estimate its severity. It can be filled out by professionals or parents of people between 3 and 22 years old. The scale consists of 42 items, responded to on a Likert-type scale, which measure the three characteristic domains adopted by the DSM-IV-TR diagnostic criteria , Planning and Ideas (PLA), Vision (VIS), Hearing (HEA), Touch (TOU), BOD, and Balance and Motion (BAL). The last two subscales refer to internal sensory modalities . From the scores obtained on the five sensory system subscales –and additional items representing taste and smell processing- a total score called Total Sensory Systems (TOT) can be obtained. Despite the terminology used on the measures referring to the sensory modalities , it must be kept in mind that the subscales assess the impairments (or differences) referred to the SP. Thus, it is not the sensory pathway, but rather the way in which the information related to a particular sensory modality is processed. On the other hand, the SOC and PLA subscales represent higher functions, where SOC (the ability to engage with others) is the subscale that measures the highest function, and PLA is the praxis subscale, which includes items about motor planning , and items about ideation .This is an integrated system of rating scales for the assessment of SP issues, praxis, and SOC in elementary school-aged children (ages 5–12). Each item is rated in terms of the frequency of the behavior on a 4-point Likert-type scale. The original SPM consists of three forms that evaluate the child's functioning in different contexts. In this study, we specifically used a Spanish translation of the original Typical (T-score range 40–59); Some Problems (T-score range 60–69); and Definite Dysfunction (T-score range: 70–80). Both forms share many structural and interpretative similarities, and so it is possible to compare different contexts. Both questionnaires present high internal consistency . Regarding validity, the different SPM subscales present correlation indexes from 0.2 to 0.5 with the subscales of the Sensory Profile and the Short Sensory Profile  were carried out to compare the characteristics of SP, praxis, and SOC of the four groups: one MANOVA to compare the four groups in the home context (parent report) and another MANOVA to compare the four groups in the classroom context (teacher report). Additionally, because the scores obtained on the TOT subscale are the sum of the scores obtained on the different sensory subscales, two ANOVAS were performed to compare the four groups on the TOT subscale: one ANOVA for the home context and another ANOVA for the classroom context. In order to control the probability of type I error, we introduced a correction factor of critical on Holm, . Third, SPM-Home Form , and the ANOVA performed with the scores on the TOT subscale .Statistically significant differences among the four groups were found as revealed by both the MANOVA performed with the scores on the As Table Typical range, whereas a small percentage (about 7%) obtained scores within the Some Problems and Definite Dysfunction ranges, indicating some difficulty. By contrast, the ASD+ADHD Group obtained the highest scores (about 74%) within the Some Problems and Definite Dysfunction ranges, whereas small percentages were obtained in the Typical range (about 26%). Thus, the ASD+ADHD Group obtained high percentages of dysfunction on all the SPM subscales: SOC (89.4%), TOT (73.7%), and Planning and Ideas (68.4%), including all the different sensory modalities subscales: BOD (84.3%), Vision (73.7%), Hearing (68.4%), Balance and motion (68.4%), and Touch (63.2%), according to the information provided by the parents of these children. Regarding the ADHD Group, about 50% of the participants obtained scores within the Typical range, and the other 50% obtained scores within the Some Problems and Definite Dysfunction ranges. The most affected sensory systems for the ADHD Group were BOD (52.6%), Balance and motion (52.6%), and Vision (52.6%). As for the ASD Group, 53.58% of the participants obtained scores within the Typical range, and 46.42% obtained scores within the Some Problems and Definite Dysfunction ranges. The most affected sensory system for the ASD Group was Hearing (61.9%).In order to obtain sensory profiles of each group, we analyzed the percentages of scores obtained by the four groups in each of the three SPM interpretative ranges. In this context, we noted that 93% of the CG obtained scores within the Comparing the three groups with neurodevelopmental disorders, in general terms, the most affected group was the ASD+ADHD Group, which obtained worse scores than the ASD Group on the BOD subscale, and worse scores than the ADHD Group on the SOC subscale. The ADHD Group obtained worse scores than the ASD Group on the BOD subscale, whereas the ASD Group did not obtain worse scores than the ADHD Group on any subscale.SPM-Main Classroom Form , and the ANOVA performed with the scores obtained on the TOT subscale . As Table Statistically significant differences among the four groups were found, as revealed by both the MANOVA performed with the scores obtained on the Typical range, whereas a small percentage (about 12.5%) obtained scores in the Some Problems and Definite Dysfunction range. By contrast, the ASD+ADHD Group obtained the highest scores (about 73%) in the Some Problems and Definite Dysfunction ranges, whereas small percentages were obtained in the Typical range (about 27%) Thus, the ASD+ADHD Group obtained high percentages of dysfunction on the main SPM subscales: SOC (94.7%), Planning and Ideas (84.2%), and TOT (79%), and the sensory modalities subscales on which the highest percentages of dysfunction were obtained were: Hearing (84.2%), Touch (73.7%), and Vision (73.7%), according to the information provided by the teachers of these children. Regarding the ADHD Group, about 48% of the participants obtained scores within the Typical range, and about 52% obtained scores within the Some Problems and Definite Dysfunction ranges. The ADHD Group obtained a high percentage of dysfunction on the Planning and Ideas subscale (68.4%), and the most affected sensory systems were Touch (52.6%) and Vision (52.6%). As for the ASD Group, about 38% of the participants obtained scores within the Typical range, and about 62% obtained scores within the Some Problems and Definite Dysfunction ranges. The ASD Group also obtained high percentages of dysfunction on the SOC (90.4%) and Planning and Ideas (85.7%) subscales, and the most affected sensory system was Touch (81%).In order to obtain sensory profiles of each group in this context, we analyzed the percentages of scores obtained by each group in each of the three SPM interpretative ranges, and we noted that about 87.5% of the CG obtained scores in the Comparing the three groups with neurodevelopmental disorders, the most affected groups were the ASD+ADHD and ASD groups because the ASD+ADHD Group did not obtain worse scores than the ASD Group on any subscale. The ASD+ADHD Group obtained worse scores than the ADHD Group on the HEA and SOC subscales, and the ASD Group obtained worse scores than the ADHD Group on the SOC subscale, but the ADHD Group did not obtain worse scores than the ASD Group on any subscale.F = 4.77; p = 0.006; η2 = 0.746]. These differences were found on the Touch (p = 0.001), SOC (p < 0.001), and Planning and Ideas (p = 0.004) subscales, with the teachers reporting higher dysfunction than the parents in all three cases.To compare the parent report with the teacher report, a MANOVA for repeated measures was performed in each of the four groups. The only group in which the MANOVA revealed statistically significant differences between the two informants was the ASD Group [Wilk's Lambda (λ) = 0.254; As expected, the three groups of children with neurodevelopmental disorders obtained higher levels of dysfunction than the group of children with typical development on most of the SPM subscales (including praxis and SOC) both in the home and classroom contexts, with some exceptions. Thus, in both contexts the CG did not obtain differences with regard to the ASD Group on the BOD subscale, nor with respect to the ADHD Group in the hearing subscale. In addition to this, in the family context, there were no differences between the CG and the ASD Group on the touch and balance and motion subscales. In all these cases, moreover, the dysfunction percentages obtained were low. However, the comorbid group (ASD+ADHD) did obtain differences with regard to the CG on all the SPM subscales in both contexts, confirming the hypothesis that these two groups  present the most different sensory profiles.Comparing the three groups with neurodevelopmental disorders, there were differences according to the context. On the one hand, in the home context, the comorbid group (ASD+ADHD) was clearly the most affected group, obtaining high percentages of dysfunction on all the SPM subscales. On the BOD subscale, the dysfunction was similar to that of the ADHD group, and in both groups it was higher than that of the ASD group. This result suggests that difficulties in proprioception –the ability to sense the position in space of limbs, fingers, and other parts of the body- may be a sensory characteristic inherent to ADHD symptomatology, coinciding with previous studies  that people with ASD show, as proposed in the framework of the Weak Central Coherence Theory (Frith and Happé, Our study has several limitations. First, children with serious behavioral problems or very low cognitive functioning were not part of the sample, so that the autism spectrum was not fully represented. Second, there is a lack of information about whether children had received or were receiving some kind of sensory intervention at the time of the evaluation. Third, the evaluation measures were reported measures, leading to possible biases. Fourth, although the SPM assesses higher processes and allows a direct comparison of performance in different developmental contexts, it does not differentiate between over-responsiveness, under-responsiveness and sensory seeking across modalities, so that it may be necessary to use other complementary instruments, such as the Sensory Profile, to plan an effective individual intervention. Fifth, groups differ by class size and also by class type, so it is possible that this aspect impact the teacher ratings of children's behavior. Finally, this research used cross-sectional data and did not study the variables over time.Children with ASD and/or ADHD can present SP impairments in different contexts, which may contribute to inappropriate behavioral and learning responses. According to the results obtained in this work, specific intervention programs should be developed to improve the sensory challenges faced by children with different diagnoses. Thus, intervention programs for children with ASD should include activities to enhance auditory and tactile processing problems, whereas intervention programs for children with ADHD should enhance proprioception, tactile, and visual processing difficulties. In both cases, intervention should also take into account the high function problems these children experience. In the case of a comorbid diagnosis, it would be advisable to implement strategies to improve BOD and balance and motion difficulties, as well as tactile, auditory, and visual difficulties. Despite these preliminary results, it must be taken into account that sensory interventions have to be individualized treatments, and further research is needed to determine a differential sensory pattern for children with ASD, ADHD, and a comorbid ASD+ADHD diagnosis.Earlier detection and management of SP problems are essential because research shows that children and adolescents with neurodevelopmental disorders have responded positively to sensory integration therapy (Schaaf et al., It is also essential to evaluate different contexts, such as the home and the school, as each context contains unique characteristics that can support and/or create challenges for the child's performance (Dunn et al., Conceived and designed the work: PS, MF, GP. Acquired data: FG, RT. Coded data: PS, MF, RT. Corrected data: MF, FG, RT. Analyzed data: MF, GP. Interpreted data: PS, GP, FG. Wrote the paper: PS, GP, MF. Drafted the article and revised it critically: GP, FG, RT.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A categorical analysis comparing subjects with and without a clinical diagnosis of ADHD showed no differences in MSSD between groups. A dimensional analysis revealed a positive relationship between MSSD and overall ADHD symptom severity and inattention across children with and without an ADHD diagnosis. Specifically, this positive relationship was found in medial prefrontal areas comprising the default mode network. These results demonstrate a link between intrinsic brain signal variability and ADHD symptom severity that cuts across diagnostic categories, and point to a locus of dysfunction consistent with previous neuroimaging literature.Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has been identified using both task-activation and functional connectivity fMRI approaches. Recent work highlights the potential for another measure derived from functional neuroimaging data, brain signal variability, to reveal insights into clinical conditions. Higher brain signal variability has previously been linked with optimal behavioral performance. At present, little is known regarding the relationship between resting-state brain signal variability and ADHD symptom severity. The current study examined the relationship between a measure of moment-to-moment brain signal variability called mean-square successive difference (MSSD) and ADHD symptomatology in a group of children (7–12 years old) with ( Attention-deficit/hyperactivity disorder (ADHD) is characterized by a lack of attention, impulsivity, and hyperactivity and affects ~11% of young individuals aged 4–17 years old  previously used in task-based   , 16 male; all right-handed, 7–12 years]. The NYU institutional review board approved all procedures for data collection and sharing and written informed consent was obtained from each participant.Data for 222 participants were downloaded from the ADHD-200 database , oppositional defiant disorder (3), depression (2), reading disorder (1), phobia (1), pervasive developmental disorder (1), and dysgraphia (1).http://fcon_1000.projects.nitrc.org/indi/adhd200/.Inclusion as a TD child was based on the absence of any current Axis-I psychiatric diagnoses as determined by administering the Kiddie-Schedule for Affective Disorder and Schizophrenia-Present and Lifetime Version (KSADS-PL) to each child and their parent. Inclusion as a child with ADHD required a clinical ADHD diagnosis based on each parent and child's responses to the KSADS-PL. IQ was evaluated using the Wechsler Abbreviated Scale of Intelligence (WASI). Finally, no psycho-stimulant drugs were administered to participants for at least 24 h prior to scanning. Full participant details can be found at TR = 2,000 ms; TE = 15 ms; flip angle = 90°; FOV = 240 mm; voxel size = 3 × 3 × 4 mm; number of slices = 33, 4 mm slice thickness; 180 volumes). Participants were asked to remain still, close their eyes, think of nothing in particular and not to fall asleep, while a black screen was presented to them.All subjects were scanned using a 3T Allegra following the diagnostic assessment. The resting state fMRI data were collected using an echo-planner imaging (EPI) sequence . Each image was defaced to ensure patient confidentiality.One high-resolution T1-weighted anatomical image was acquired using a magnetization prepared gradient echo sequence (MP-RAGE: The data were preprocessed using the Data Processing Assistant for Resting-state fMRI Advanced Edition (DPARSF-A) toolbox  and p < 0.05 for cluster-wise (Guassian Random Field theory corrected) significance thresholds.All analyses were carried out on subject-level whole-brain voxel-wise MSSD maps using ordinary least squares (OLS) regression in FSL , demonstrating the preservation of spatial MSSD patterns between the two preprocessing pipelines. Similar spatial representations of positive correlations between MSSD and ADHD symptomatology were also observed  and also between average MSSD values within the ventral MPFC and ADHD-inattentive scores .In order to examine the influence of head motion on brain signal variability, an additional OLS regression was run using mean FD values to predict MSSD values. The results showed both positive and negative relationships between FD and MSSD across various areas of the cortex ,  , with researchers proposing that atypical variability may have cognitive and behavioral consequences for afflicted individuals  for voxel-wise correction. Previous research on task-based fMRI data suggests that a stricter voxel-wise criterion (p < 0.001) in conjunction with a cluster-wise criterion (p < 0.05) provides better protection against type I errors (Eklund et al., One limitation of the current study may be related to the significance threshold (Another concern is the use of participants with both a combined diagnosis and inattentive diagnosis of ADHD. Previous research has shown that differences in functional connections can be observed between ADHD-combined and ADHD-inattentive diagnostic groups in fMRI research (Fair et al., The current study demonstrates that resting-state BOLD signal variability is related to dimensional, but not categorical differences in ADHD symptomatology. The dimensional analysis demonstrated that areas within the medial PFC are positively correlated with measures of the ADHD index and ADHD inattentive symptom severity. These results provide initial evidence that resting-state brain signal variability in children is a viable avenue of investigation to identify brain function related to ADHD symptomatology.JN, AH, and LQU designed the study. JN, ES, WV, and TB analyzed the data. JN and AH contributed unpublished analytic materials. JN, ES, WV, TB, AH, and LQU wrote the manuscript and approved the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.n = 20,183 cases, n = 35,191 controls) and Swedish population register data .We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project , potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases . In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals .Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence. SEE COMMENTARY ON PAGE e55Attention-deficit/hyperactivity disorder (ADHD) is a common , highly heritable 70%–80%) neurodevelopmental disorder 0%–80% neIn children, boys show a two to seven times higher ADHD diagnosis rate than girls One possibility is that female ADHD is qualitatively different from male ADHD. Although the majority of twin studies have not detected any quantitative or qualitative sex differences in ADHD heritability The absence of extensive sequencing data currently precludes analogous analyses of rare genetic variants. Instead, to evaluate whether such variants play differential roles in male and female individuals with ADHD, we used risk for comorbid brain-related developmental disorders  and rare syndromic phenotypes  as proxies for possible presence of de novo or rare segregating alleles. Rare, highly deleterious (including noninherited) genetic variation has been implicated in such phenotypes Aside from heterogeneity, prevalence differences may be caused by a female protective effect, whereby female individuals are resilient to developing ADHD and thus require a higher burden of genetic liability to develop it. Three family studies have observed indirect evidence for this hypothesis in the form of increased risk of ADHD in first-degree relatives of affected female individuals compared with affected male individuals, suggesting that families with an affected female individual may have a higher burden of genetic risk We present a series of analyses to test the qualitative and quantitative difference hypotheses for the biased sex prevalence in ADHD. First, autosomal common variant data were used to estimate the genetic correlation of ADHD in male and female individuals. We then used population register data to examine whether female individuals with ADHD are at an increased risk for comorbid developmental conditions compared with affected male individuals. Next, genome-wide autosomal SNP data were used to test whether female individuals diagnosed with ADHD carry a higher burden of common risk variants than affected male individuals. Finally, using register data, we tested whether relatives of female individuals with ADHD are at an increased risk for ADHD compared with relatives of diagnosed male individuals.Data for ADHD cases and controls were available from the Psychiatric Genomics Consortium (PGC) and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). See GWAS publication for full details of quality control, imputation, and principal components analysis n = 20,183 cases  and n = 35,191 pseudocontrols/population controls . Analyses that were restricted to European-only samples consisted of 19,099 cases and 34,194 controls. ADHD GWAS summary statistics were also available from research participants of the personal genetics company 23andMe Inc.  .The iPSYCH samples were genotyped, processed, and analyzed in 23 separate waves. See n = 7,531,543 common variants (hereafter PGC + iPSYCH). GWAS summary statistics can be downloaded at https://www.med.unc.edu/pgc/results-and-downloads.Sex-specific logistic regression GWAS analyses of imputed autosomal data were performed in each PGC study and iPSYCH wave separately. Results were filtered for each study/wave based on minor allele frequency, imputation quality, call rate, and expected minor allele frequency in cases. Sex-specific GWAS results for samples of European ancestry were meta-analyzed and also filtered based on sample size and presence of each SNP in both sets of results. This yielded results for Bivariate linkage disequilibrium (LD) score regression (LDSC) z-score transformations; ORs can be interpreted as increase in risk of the outcome per standard deviation in PRS. Logistic regression analyses including principal components were used to test for association of PRS with sex in cases . Results of these leave-one-study/wave-out analyses were meta-analyzed.A leave-one-study/wave-out approach was used to maximize power and maintain independent target and discovery samples for PRS analyses using the standard approach n = 77,905 ADHD cases and n = 1,874,637 population controls). See Analyses of Swedish register data were based on all individuals of known parents born in Sweden between 1987 and 2006, living in Sweden at least until 12 years of age .We estimated whether risk of ADHD in siblings of female individuals with ADHD was higher than that in siblings of affected male individuals after adjusting for sex of the comparison sibling. Analyses stratified by sex of the comparison sibling are also presented. Analyses were restricted to pairs of full siblings where at least one child had an ADHD diagnosis (rg) results for male and female ADHD from bivariate analyses using GREML and LDSC (see rg estimate in the full dataset (PGC + iPSYCH) was near 1. Similar results were found for bivariate GREML analyses in both iPSYCH and PGC and for the LDSC analyses in the iPSYCH dataset. The LDSC estimate in the PGC dataset was lower, but large standard errors were seen in this dataset for both methods.rg (SE) = 1.13 (0.22)]. Cross-dataset rg values for PGC male individuals with iPSYCH male and female individuals were also not significantly different from 1. Estimates for PGC female individuals with iPSYCH female individuals were lower (significantly different from 0 and 1), although this is likely related to the small sample size of the PGC female individuals (n = 1067 cases and n = 5178 controls).Additional cross-dataset and cross-sex LDSC genetic correlation estimates were used to assess the extent of heterogeneity across PGC and iPSYCH see . The gen2 was estimated at 0.123 (SE = 0.025) in female individuals and 0.247 (SE = 0.021) in male individuals . No SNPs surpassed the genome-wide significance threshold in the female-only GWAS . . Narrowing the focus to only ADHD cases also finds no genome-wide significant differences between male and female cases . Secondary analyses of severity of ID (where information was available) indicated that this weak association signal came from mild ID (IQ = 50–70), not moderate (IQ = 35–49) or severe/profound (IQ < 35) ID  ID . Interacp = .28, mean R2 [SE] = .0019 [.00039]). Sensitivity tests were run excluding the data from 23andMe and non-European ancestry individuals and then also not including sex as a covariate in the discovery GWAS analyses; results remained similar   . Mothers.00024]) .Figure 4p = 4.1xE-91, mean R2 [SE] = .039 [.0034]) and male individuals . In this analysis, several individual PGC studies did not show a significant association with case-control status in female individuals; this is likely due to low power .There was a clear association of ADHD PRS with ADHD case status, with similar differences in PRS between cases and controls observed for female individuals ; results stratified by comparison sibling sex were similar for male individuals  and female individuals . Covarying for presence of ASD, congenital malformations, and ID in the proband did not affect the overall results .To test for evidence of increased risk for ADHD in siblings of female individuals with ADHD, we used Swedish population data to select sibling pairs where at least one child had ADHD. The results showed that siblings of female individuals diagnosed with ADHD are at higher risk for ADHD than siblings of affected male individuals  and Swedish population register data . We demonstrated a high level of genome-wide autosomal genetic correlation for ADHD across sex and found no increase of polygenic burden in affected female individuals compared with affected male individuals. However, in register-based data, we observed that siblings of female individuals with ADHD are at increased risk for ADHD compared with siblings of affected male individuals. The results also suggested that female individuals diagnosed with ADHD may be at an especially high risk for certain comorbid developmental conditions.We tested two specific hypotheses for the male bias in ADHD: first, that sex-specific genetic heterogeneity may affect prevalence rates via clinical heterogeneity in ADHD diagnosis by sex, and second, that female individuals affected with ADHD may carry an increased burden of genetic risk variants compared with affected male individuals. We analyzed autosomal common variant data from the largest available ADHD case-control GWAS sample (The observed high SNP-based genetic correlation (consistent across two methods) suggests that largely the same common autosomal risk variants are involved in ADHD for both sexes. While sex-specific heterogeneity from common autosomal variants seems unlikely based on our results, we cannot rule out the possibility that heterogeneous effects exist for rare or nonautosomal variation or that with increased sample sizes, weaker effects of common variant heterogeneity could be detected.Indeed, the epidemiological analyses of Swedish population data suggest some degree of clinical and/or etiological heterogeneity. ADHD was associated with comorbid diagnoses of developmental conditions in both sexes. The strength of association was greater in female individuals for ASD, congenital malformations, and (to a lesser extent) mild ID, but it was similar for both sexes for motor problems, epilepsy, and chromosomal abnormalities. There are several possible explanations for these findings.First, female individuals with ADHD may have a higher than expected risk of comorbid severe conditions and so may have a higher level of clinical heterogeneity as compared with male cases. This could indirectly point to a greater role of rare deleterious variants in female individuals with ADHD because such variants are strongly implicated in some of the comorbid conditions assessed An alternative explanation for the results is that ascertainment and diagnostic biases, where female individuals are more likely to be diagnosed with ADHD if they have a more severe phenotypic presentation, could be involved. Individuals who receive one diagnosis become the focus of clinical attention and are more likely to receive subsequent diagnoses, whereas individuals with less complex phenotypes might not come to clinical attention. If female individuals are routinely underdiagnosed with ADHD or other neurodevelopmental disorders, this issue may disproportionately affect ascertainment of female cases, leading to the observed pattern of results. Other possible sources of bias include typical exclusion criteria for diagnosing ADHD  and the possibility of an inflated false positive rate of diagnoses due to diagnostic uncertainty and change over time. We limited the impact of the latter by considering diagnoses only in individuals with at least two reported diagnoses. Although the results are consistent with increased etiological heterogeneity in female individuals with ADHD, studies of rare variation are required to rule out these alternative explanations.Epidemiological analyses also showed that siblings of female individuals diagnosed with ADHD were at higher risk for being diagnosed with ADHD than siblings of diagnosed male individuals. This confirms results from previous family studies Contrary to smaller studies p = .31; see One possibility is that a higher degree of genetic heterogeneity within female individuals masked any differences in PRS burden by sex in the current study. Common and rare variants may contribute additively to ADHD risk, with non-CNV carrier cases having lower ADHD PRSs than cases with large rare CNVs Although the focus of this paper is on possible genetic sources of influence on ADHD sex bias, other factors, such as ascertainment and diagnostic biases, may play an important role. Female individuals are more likely to be diagnosed with the predominantly inattentive subtype of ADHD, whereas male individuals are more likely to be diagnosed with the combined subtype of ADHD and present with hyperactive-impulsive and disruptive behavioral problems Another possible contribution to sex bias, beyond the scope of the current study, is the role of sex hormones and chromosomes. There is evidence for a specific role of sex hormones  and sex chromosomes  in early brain development and neurodevelopmental disorders such as ADHD 2 estimates using two methods (similar in both sexes once nonrandom sample ascertainment is taken into account via sample size matching), clear deviation of test statistics on sex-specific GWAS quantile–quantile plots, and significantly higher overall PRSs in cases compared with sex-matched controls. Top hits from sex-specific GWAS analyses corroborate results from a combined analysis of both sexes The results of this study demonstrate a clear polygenic contribution from common autosomal genetic variants to ADHD in both sexes, as evidenced by moderate SNP-hThe high genetic correlation and lack of difference in polygenic burden between male and female ADHD cases support combining GWAS data from both sexes in ADHD meta-analyses and further suggest that current clinical practices of diagnosing ADHD are capturing a clinical phenotype that is similar at the level of common genetic risk variants in both sexes. Thus, our results indicate that genome-wide autosomal common variants largely do not explain the observed sex bias in ADHD prevalence. On the other hand, the epidemiological results also suggest some degree of clinical heterogeneity, with ADHD showing a stronger phenotypic association with comorbid ASD, congenital malformations, and mild ID in female individuals. We also found evidence for a modest increase in familial risk for ADHD in female individuals based on sibling analysis. Further work simultaneously examining variants across the spectrum of frequencies is needed to comprehensively determine the role of genetic risk in the sex bias in ADHD prevalence.


Pteris vittata (PV) is capable of accumulating large quantities of As in its aboveground tissues. Transformation to AsIII and vacuolar sequestration is believed to be the As detoxification mechanism in PV. Here we present evidence for a preponderance of exocellular As in fronds of Pteris vittata despite numerous reports of a tolerance mechanism involving intracellular compartmentalization. Results of an extraction experiment show that 43–71% of the As extruded out of the fronds of PV grown in 0.67, 3.3 and 6.7 mM AsV. SEM-EDX analysis showed that As was localized largely on the lower pinna surface, with smaller amounts on the upper surface, as crystalline deposits. X-ray fluorescence imaging of pinna cross-sections revealed preferential localization of As on the pinna surface in the proximity of veins, with the majority localized near the midrib. Majority of the As in the pinnae is contained in the apoplast rather than vacuoles. Our results provide evidence that exocellular sequestration is potentially a mechanism of As detoxification in PV, particularly at higher As concentrations, raising concern about its use for phytoremediation.The arsenic (As) hyperaccumulating fern species  Pteris vittata (PV) was first reported in 20011. Pteris vittata has the ability to uptake and translocate large amounts of As to its shoots3. Due to its potential in phytoremediation of As, the mechanism of As hyperaccumulation in PV has been the subject of intense research.The existence of the As hyperaccumulating fern species, 4. AsV is reduced to AsIII by arsenate reductase (AR) in the plant5. Earlier reports showed that AsV is reduced to AsIII in the fronds6, but later reports suggested that the reduction occurred in the roots8. Recently, two constitutively expressed AR proteins in both fronds and roots has been reported in sporophytes of PV9. Speciation of As is now believed to be dependent on As concentration in the growth media12. When AsV levels are low, the reduction can occur in the roots, but at higher concentrations, a part of the reduction occurs in the fronds12.Once As is taken up by roots, translocation to fronds occurs rapidly13. Within the pinnae, AsIII is mostly localized at the tips, in the blades proximal to the veins, and within the pseudoindusium13; whereas AsV is mainly localized within the veins. At the cellular level, As was reported to be localized in the upper and lower epidermal cells and trichomes of the fronds15. Although several reports have mentioned that As is sequestered in the vacuoles in PV15, there seems to be no definitive evidence of the same. One study speculated that As was localized in the vacuoles because SEM-EDXA analysis showed As mainly in the central part of the cells in fresh fronds6, and central part of the cells is occupied by vacuoles. In a more recent subcellular fractionation study, 78% of the As in PV pinnae was recovered in the cytoplasmic supernatant fraction16 which consists of cell and vacuolar sap, hence the authors speculated that As was localized in vacuoles. Other indirect evidence of vacuolar sequestration originated from the identification of arsenite transporter proteins in PV, localized in vacuolar membranes17.In the fronds, As is concentrated at the tips of the apical pinnae, with levels decreasing toward the basal pinnae18, which is common in excluder, rather than hyperaccumulator plants19. Between 6–20% As is effluxed into the medium by PV roots21, compared to 80–90% for rice23. No evidence of efflux through PV fronds existed until As leaching from foliage was reported recently using a simulated precipitation experiment24, where 2–7% of the total foliar As was leached. Water-soluble As from the apoplast was the primary source of the leached As24. Another paper reported the secretions from hydathodes in PV contain high levels of As, using SEM-EDX analysis25. To verify and further elucidate the phenomenon of As loss through the aboveground parts of PV, we performed detailed SEM-EDX, X-ray microprobe synchrotron analysis, and XRF mapping of cross sections of pinnae after exposing PV to various concentrations of AsV.Another strategy adopted by plants to cope with As is to efflux it from roots1.Figure −1 based on wet plant weight) extracted from the fronds after being gently shaken with deionized water for 4 h. Residual As in the shoot tissues was estimated after drying and acid digestion of the fronds  and As in PV fronds13. Increased glutathione (GSH) and PC2 (a dimer of GSH) concentrations in PV fronds treated with As28 has also been reported. The presence of As(V) in the pinnae could be due to use of higher concentrations of As in the growth medium, which resulted in incomplete reduction of AsV to AsIII18.XANES scans taken at locations throughout the leaflet are presented in Fig. 2S3 Fig. . The pre2) for As vs. K, As vs. Ca and As vs. S in the midrib vein are 0.97, 0.96, and 0.77 respectively. The strong positive spatial correlation between As and K in cross-section . After two weeks, AsV stock in the form of sodium arsenate was added to achieve initial concentrations of 0, 0.67, 3.3, 6.7, 10 and 13.3 mM As. Plants were grown in triplicates, and a set of controls without As was included. Plants were harvested after 14 days and media samples were analyzed for total As using ICPMS to determine uptake by PV. In order to estimate As removal from the fronds, harvested fronds in triplicate were placed with deionized water for 4 h with gentle shaking in an orbital shaker. The wash solution was sampled at regular intervals, and analyzed for total As using ICPMS. Arsenic remianing in the frond after water extraction was estimated using ICPMS after drying the fronds followed by acid digestion. Speciation of As in the water extract from the fronds was determined using HPLC coupled with ICPMS31. Mean comparison was conducted using JMP version 11.A JEOL 5400 LV SEM attached to KEVEX Sigma energy dispersive X-ray spectrometer (SEM-EDX) was used. Fronds from PV plants grown in 13.3 mM As before and after the extraction experiment and control fronds grown without As were subjected to SEM. All samples were viewed with at 20 kv with a working distance of 21 cm, in low vacuum mode. Fronds were freeze fractured in liquid nitrogen and dehydrated for 24 hours. Samples were mounted on carbon tape attached to aluminum stubs. For each sample, an adaxial, abaxial, and a fractured cross section was mounted and viewed.Spatially resolved micro X-ray fluorescence (µ-XRF) maps were collected in combination with micro-focused As K-edge X-ray absorption near-edge spectroscopy (µ -XANES) spectra at beamline X27 A of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory, Upton, New York. Fresh fern pinnae from plants grown in 6.7 mM As were fixed onto slide frames with Kapton tape, and mounted on an XYZ motorized sample stage positioned at 45° incidence to the beam. A Si(111) monochromator was used for energy selection, and the beam was focused with Kirkpatrick–Baez mirrors to produce a spot size of ~10 µm × 15 µm on the sample. X-ray fluorescence was measured with a 13-element Canberra Ge array detector positioned at 90° to the incident beam. Mapping was done in fly scanning mode at an energy of 13.0 keV, using a pixel size of 0.02 mm and an integration time of 0.05 s.2HAs(V)O4, NaAs(III)O2, and orpiment (As(III)2S3) to assist data interpretation of the As fern data. For all XANES scans, the monochromator was calibrated by assigning the top of the white line of the spectrum of As(V) incorporated in topaz to a value of 11875 eV. Data processing involved averaging and normalizing the XANES spectra using WinXAS 3.132Micro-XANES spectra of the As K-edge (11867 eV) were collected at various locations throughout the pinnae, using steps and counting times of 5.0 eV and 3 s, 0.5 eV and 6 s, 1.0 eV and 6 s, and 5.0 eV and 3 s in the 11767–11857, 11857–11907, 11907–11967, and 11967–12167 eV energy ranges, respectively. Two or three scans were collected per spot, and averaged to improve signal:noise. XANES spectra were also collected for the reference compounds NaFreshly harvested frond pinnae grown in 6.7 mM As were oriented with the tip pointing upwards and placed into a well containing OCT  embedding medium  then rapidly cooled to −20 °C for preparation of the tissue cryosections. Specimens were cryotomed at −15 °C to 20 um thick cross-sections using a cryotome CM 1900 . Sections were made at 0.5, 1 and 2 mm from the tip of the leaflets. Tissue sections were mounted onto silicon nitride windows  and stored in a desiccator until analysis by X-ray microprobe. X-ray microanalysis of tissue sections was conducted at the APS sector 13 GSECARS beamline using a spot size of 1 × 2 um, a pixel size of 2 um and a transit time of 100 ms.Supplementary Information


Especially, polyethylene glycol (PEG) has been proven as the vital template to form D-BM microsphere. Importantly, the as-prepared D-BM microsphere presents pH-dependent superior adsorption behavior and remarkable visible light photocatalytic activity for degradation of organic dyestuffs (Rhodamine B/RhB and Methylene blue/MB), far exceeding those for the pure Bi2S3 and MoS2. It is understandable that D-BM with high surface area possesses more active sites and promotes light utilization due to the unique porous structure with outspread wings. Besides, based on the experiments and theoretical calculations, the staggered type II band alignment of D-BM permits the charge injection from Bi2S3 to MoS2, subsequently accelerates the separation and restrains the recombination of carriers, leading to excellent photocatalytic activity, as well as the photoconductance and photoresponse performance (with Ilight/Idark ratio 567).The enhanced light-harvesting capacity and effective separation of photogenerated carriers in fantastic hierarchical heterostructures enjoy striking attention for potential applications in the field of solar cells and photocatalysis. A three-dimensional (3D) dandelion-shaped hierarchical Bi The intense demand for photocatalysis applying to the pollutants degradation and the effective solar energy conversion keeps moving due to the worsening environment and energy crisis12345678101113141552S3, with a typical band gap (1.3–1.7 eV) for solar photovoltaic, has attracted lots of research interests17182S3 nanocrystal with various morphologies have promising applications in solar cells, photodetectors, gas sensors, electrochemical hydrogen storage and X-ray computed tomography imaging due to the suitable band gap202122242S3 has been restricted because of the toilless recombination of photogenerated carriers and therewith the low quantum yield. Hence, as a feasible method so far to prolong the lifespan of electron-hole pairs, establishing composite structures with metal oxides, metal chalcogenides or 2-dimensional (2D) hexagonal graphene, for instance Bi2S3/Bi2WO6, Bi2S3/TiO2 and Bi2S3/Pd4S, has been paid significant attention122627282S3 skeleton, keeping superiority in large active contact area, is considered to have potential in synergistically enhancing the photocatalytic features.Typically, as a eco-friendly lamellar-structured semiconductor, Bi2 nanostructures have been synthesized with plentiful morphologies of nanosheet, nanoribbon and nanosphere3536372 be widely applied to biosensors, memory, capacitors, logic circuit devices, and lithium batteries39402 possesses a large surface area and massive active sites, which can provide sufficient contact and effective reactions2 has been proven to be promising and it also opens opportunities for optoelectronic applications. Zhou et al. have successfully fabricated MoS2 nanosheet-coated TiO2 nanobelt heterostructures, which showed a high photocatalytic hydrogen production and strong photocatalytic degradation of the dye molecules2-TiO2 nanocomposite forcefully retard the photogenerated electron-hole recombination. Moreover, Chen et al. have put forward a bottom-up strategy of solvothermal method for 2D MoS2 nanosheets composites, which exhibited preeminent properties in biomedicine and realized considerable applications in photothermal regression of tumor43The wide researches and successful applications of graphene recently have triggered great attention on 2D-layered materials. The 2D transition metal dichalcogenides (TMD) exhibit ultrathin physical characteristic, excellent optical, electronic, mechanical properties and potential applications in field-effect transitions (FET) and sensing devices303132332S3@MoS2 microsphere using a facile hydrothermal method for the first time. Intriguingly, the layers of MoS2 coating likes the wring of the dandelion. This unique architecture offered a high light utilization as a result of large surface area and massive active sites for reactions. Moreover, the formation of the staggered type II band alignment in D-BM made a prolonged lifespan of electron-hole pairs, based on calculated energy band positions and the corresponding electronic structures. Obviously, evaluated by the degradation of Rhodamine B (RhB) and Methylene blue (MB) under visible light, the as synthesized heterostructure exhibits more remarkable adsorption and visible light photocatalytic properties than the pristine Bi2S3 and MoS2. Also, it presents improved photoresponse property with a high Ilight/Idark ratio of 567.In this work, we propose a novel heterostructure of 3D-dandelion Bi2S3, MoS2 nanoflowers and their composites were characterized by XRD analysis. Pattern I corresponded well to the lattice planes of orthorhombic Bi2S3  without some impurity as Bi2O3. And pattern II can be indexed to the standard peaks of hexagonal MoS2 . As for hierarchical D-BM structure , the weak diffraction peak at 2θ = 14.2°, corresponding to the MoS2 lattice plane of (002), can be inferred that the few-layered MoS2 petals have been broken by D-Bi2S3. Raman spectroscopy was further utilized to identify the hybrid production. In 2 can be observed at 375 and 402 cm−1 from the local amplification, which correspond to the E2g and A1g vibration modes, respectively2S3 microspheres are located at 107 cm−1 and 260 cm−1, which can be assigned as the Ag and B1g modes2S3 and MoS2 both are presented in the result of their hybrids, demonstrating the successful incorporation of D-BM structures. Note that there is a blue shift of the B1g mode compared to the pure Bi2S3. It probably suggests the surface strain is due to the novel coated MoS2 on each Bi2S3 nanorod.As shown in 2S3 microspheres in different magnifications. It can be seen that the Bi2S3 structures are distributed in the shape of irregular microspheres with the average diameter of 5 μm. Apparently  and (101) planes of Bi2S3, respectively2 exhibits the lattice spacing of 6.19 Å, which matches well with the (002) planes of hexagonal MoS22S3 (3.4148 nm), which is eleven intervals of the adjacent S atoms on the (001) crystal surface of MoS2 (0.3169 nm × 11)2S3 nanorods might be available for the growth of the MoS2 nanosheets to form the heterostructure between the mutual effect of S and Bi atoms. Thus, it can be inferred that the MoS2 sheets, with about 5–8 layers, embellished at the surface of the Bi2S3 rods. Moreover, the selected area electron diffraction (SAED) pattern (inset of 2S3 (bright diffraction spots) and layered superimposed MoS2 sheets (diffraction rings). In order to accurately confirm the elemental composition and spatial distribution, energy dispersive X-ray spectrometry (EDS) analysis in In addition, a sequence of TEM and HRTEM images of D-BM nanocomposite have been employed to reveal more specific structural information. In EM image , the latinset of  further 2S3, MoS2, and D-BM (5 MBS) heterostructures. The 2S3 and MoS2 (Note that C element acts as reference and O element comes from the absorbed oxygen). After the second hydrothermal reaction, the overall XPS spectra in f (158.46/163.76 eV) and Mo 3d (228.84/231.99 eV) for pure Bi2S3 and MoS2, respectively. In addition, the XPS spectrum of the hybrids in f7/2, S 2p3/2, S 2p1/2, and Bi 4f5/2, respectively. The high resolution Mo 3d , S 2p (1.25 eV), and Mo 3d (3.15 eV) peaks disclose the existence of Bi3+, S2−, and Mo4+, based on the reported results.We also performed XPS analysis to elucidate the surface chemical composition and valence states of the pristine Bion Mo 3d  binding 2S3, the formation process has been investigated by SEM at different reaction times, as shown in μm) have been formed and proven to be orthorhombic Bi2S3 by XRD analysis (2S3. As the reaction proceeded (3 h), some actinomorphic-shaped Bi2S3 (diameter of 5 μm) can be captured in 2S3 nanorods are rough and inhomogenous, indicating a rapid growth of Bi2S3 microspheres. By prolonging the reaction time to 8 h, massive intact D-Bi2S3 microspheres have been successfully synthesized. Then the products under hydrothermal condition have been collected at 5 h, 8 h, and 12 h. The SEM images in 2 nanosheets become increasing and orderly along with the prolonged reaction process. It can also be verified through the related XRD survey  plane provides the convincible proof for the formation of the MoS2 coated Bi2S3 nanocomposites.The growth mechanism of the D-BM nanomaterials has been studied for potential applications and controllable synthesis of other novel structures. For D-Bianalysis , which iD survey . At the 2S3@MoS2 structure is illustrated in 3+-thiourea complexes, initially. Under elevated temperature, these complexes decomposed, accompanied by shaping into needle-like nanospheres with nucleated Bi2S3482S3 grew gradually to improve the rough surface, at the expense of Bi2S3 particles or rods. It can be attributed to the typical Ostwald ripening process, which could significantly reduce the total surface free energy2S3 microspheres with short tomentum ascertain the role of PEG as the important template. Finally, the 3D D-Bi2S3 microspheres could provide available high active sites for the growth and insertion of MoS2 nuclei, leading to the hierarchical and porous framework.Based on the results of the time-dependent experiments and analysis, the probable morphology evolution process of the hetero-Bi2/g for the hybrid. Obviously, the characteristics with enlarged surface area and porosity of the composite recognized the embedded structure of MoS2 nanosheets into Bi2S3 microspheres. By the Barrett-Joyner-Halenda analysis, the pore-size distribution of Bi2S3@MoS2  and MoS2 (50%) are indistinctive after 40 min. Whereas, when the MoS2 was introduced to Bi2S3, the decomposition rate significantly increases to near 92%. The time-dependent absorption spectra of RhB solutions by D-BM and others were shown in 2 have massive dege active sites, where strong interaction occurs with dye molecules51522 may lead to several internal intersections, which make it possible to bring much more effective area for absorption. Likewise, it is favoring to transfer excited carries between MoS2 and Bi2S3 heterostructure, leading to reduce the recombination efficiency and prolong the lifetime of carries. In addition, the photocatalytic activity can also be related to the amount of the coated MoS2 nanosheets, which highlights the optimization of 5 MBS. As for 2 MBS samples, fewer MoS2 nanosheets cannot provide enough multiplex refraction for the incident path, as well as the more active site for the adsorption of reactant molecules. On the other hand, 8 MBS samples with superabundant MoS2 nanosheets impeded the transformation of photogenerated carries in reverse, thus facilitating their recombination. To make a more specific comparison, the reaction kinetics of all catalysts have been linear fitted as ln (C0/C) = kt according to Landmuir-Hinshelwood mechanism shown in 54550 are the real-time concentrations and initial concentration of RhB, t and k denote the irradiation time and the overall photodegradation rate constant, respectively. The rate constant of pristine Bi2S3 and MoS2 are 0.007 and 0.016 min−1. Nevertheless, a dramatic improvement (0.073 min−1) of 5 MBS can be achieved. Specifically, the increased reaction rates were attributed to the unique porous structure, with faster mass transport and more accessible active sites, resulting in an increased reaction rate. The stability and reusability of the composites (sample 5 MBS at pH = 7) also have been evaluated under irradiation by collecting and reusing them over 3 cycles. As shown in To demonstrate the photocatalytic ability of the D-BM heterostructures, photodegradation of RhB in aqueous solution has been investigated under visible-light irradiation. In k = 0.157 min−1  and photocatalysis survey have been conducted. Note that the initial pH of the RhB solution was adjusted by HCl and NaOH solution (1 M). The 57 min−1  at pH = 57 min−1  and phot2S3 and MoS2, which favors the separation of the photoinduced carriers. However, a small percentage of the samples might had undergone hydrolysis which was unavoidable, taking the slight decrease through cycling experiments and photocorrosion into consideration.In order to further investigate the stability of the catalyst, the XRD and EDS mapping results after adsorption and photodegradation tests have been shown in π-bond of RhB and MB can beneficially excite electrons with irradiation, as well as the existence of the functional groups (-COO−) as the shown molecular structure of RhB in in situ degraded promptly  edge potential and Ee refers to the free electrons energy based on the hydrogen scale (4.5 eV). Based on previous studies, X is the electronegativity of the corresponding semiconductor (5.28 eV for Bi2S3 and 5.32 eV for MoS2), expressed as the geometric mean of the electronegativity for the component atoms, and the band gap energy Eg of Bi2S3 and MoS2 are 1.33 eV and 1.3 eV, respectively12EVB and ECB  of Bi2S3 are estimated to be 0.12 eV and 1.45 eV, both higher than those of MoS2, with ΔEVB = 0.02 eV and ΔECB = 0.05 eV, respectively. Compared with the pure samples, the heterostructure of D-BM presents an obvious enhanced absorption . I–V) curves of NR-BM based nano-photodetector exposed to 650 nm illumination (1.0 mW cm−1) and in dark, respectively. It is obvious that the quasilinearity of the I–V curves indicates the formation of an good Ohmic contact between Au electrode and NR-BM interface. With illumination, the NR-BM shows a remarkable photocurrent reaches about 0.703 μA under −1.5 V bias voltage, resulting a higher Ilight/Idark ratio to about 567, which compared to the NR-Bi2S3 of 126 with the shortened lifetime of the electron-hole pairs  serves as a critical metric to the photodetector sensitivity, which is defined as R(AW−1) = Ip/PoptIp and Popt are the photocurrent and incident light power, respectively. Based on the results, the R of the D-BM device is estimated to be 13.3 AW−1. Consequently, the improvement of photoconductivity and photoresponse performance supports the efficient carries separation resulting from the heterostructures of dandelion-shaped Bi2S3@MoS2.Besides photocatalysis, the as-synthesized D-BM hybrid is expected to have improved photoconductance and photoresponse properties compared with the pure Bi devices  were fabInset of . The ele mW cm−1 . ClearlyInset of  in the N2S3 and MoS2 have been shown in p and few contributions of Bi 6s, while the bottom of CB are mostly Bi 6p and S 3p for Bi2S3, with calculated Eg = 1.44 eV. As for MoS2 , the top of VB originates from Mo 4d, and the bottom of CB are Mo 4d and some hybridization with S 3p. Note that 2 (top) and Bi2S3 (down). By aligning the Fermi level relative to the vacuum energy level, the obtained work functions for Bi2S3 and MoS2 are 4.88 and 5.00 eV, respectively. Due to the differential work functions, a built-in electric field from Bi2S3 to MoS2 can be established near the interface. Thus the built-in electric field of the composites is expected to facilitate the separation of photo-generated carriers. It can be concluded that the theoretical calculations of the band energy positions  of Biositions  keep hig2S3 microspheres coated with layered MoS2 nanosheets. The novel heterostructure with unique porosity and intimate interfacial contact can provided efficient visible-light utilization and penetrable paths for reactant molecules to reach the inner structure. Compared with the pristine Bi2S3 or MoS2, the as-synthesized D-Bi2S3@MoS2 composite has exhibited much higher adsorption behavior and photocatalytic activity under visible-light irradiation. The formed staggered type II band alignment of Bi2S3@MoS2 has expected to promote the separation of carries, accelerate the transportation and prolong lifespan of electron-hole pairs, which can be verified by the excellent photoconductance and photoresponse properties. Correspondingly, the Bi2S3@MoS2-0.5 mol (5 MBS) has been proven to achieve an optimal photocatalysis performance, highlighting the importance of novel core/shell heterostructures for environmental remediation and solar energy harvesting applications in the future.In summary, a green strategy based on the hydrothermal method has been developed for the fabrication of hierarchical 3D dandelion-shaped Bi2S3 microspheres were prepared at 180 °C2 nanosheets onto Bi2S3 microspheres . Further information about the experimental details are available in the ESI.Generally, the D-BM heterostructure were synthesized by a two-step hydrothermal method. Firstly, the dandelion-shaped Biλ = 1.5418 Å). Field emission scanning electron microscopy  was employed to investigate the morphologies of the synthesized samples, equipped with an energy dispersive X-ray spectroscopy (EDS). For detailed insight into the 2D-layered MoS2 coated Bi2S3, Transmission Electron Microscope (TEM) and high resolution transmission electron microscopy (HRTEM) studies were analyzed at the accelerating voltage of 200 kV. X-ray photoelectron spectroscopy  measurements were carried out with Mg-Kα radiation (hν = 1253.6 eV). Raman spectroscopy experiments were implemented by Jobin-Yvon LabRAM HR 800 micro-Raman spectrometer using a 532 nm line from a He-Cd laser. The absorption spectra have been obtained using the PerkinElmer Lambda 950 spectrophotometer in dilute solution. The specific surface area were calculated by the Brunauer-Emmett-Teller (BET) method .The crystallinity and purity of the resulting products were assessed by X-ray diffraction  equipped with Cu Kα radiation  under visible light irradiation. More details about the photocatalytic tests have been provided in ESI. In addition, transient photocurrent responses for the as-prepared catalysts were performed over an electrochemical analyzer  in a standard three electrode system. Under the irradiation of simulated sunlight (500 W Xe lamp with a cutoff filter), the prepared samples acted as working electrode (ITO as supporter). A Pt wire worked as counter electrode, and Ag/AgCl (saturated KCl) as reference.2S3@MoS2 nanorods (NR-BM) from D-BM microspheres by oscillating  were drop-deposited on the SiO2 (300 nm)/Si substrate. Then the Au electrodes (100 μm × 150 μm) were defined on the NR-BM film by photolithography and high-vacuum electron beam (EB) evaporation process. The optoelectronic properties of the fabricated device were measured by a semiconductor parameter analyzer system (Keithley 4200-SCS) with the illumination laser of 650 nm.The photoconductance and photoresponse behavior of the D-BM was studied based on the nano-photodetectors. Typically, the disrupt Bi2S3 and MoS2) are 600 eV/450 eV and the 3 × 8 × 3/5 × 5 × 1 Monkhorst-Pack k-point mesh have been employed for the Brillouin-zone integration. The electronic structures were calculated with the optimized lattice geometries. Based on the convergence criteria, both energy and force were less than 10−5 eV and 0.01 eV Å−1, for the fully relaxed initiating structures, respectively.In the present work, the first-principles calculations of the heterogeneous structure have been performed, to provide the theoretical basis of the promoted photocatalytic activity. In details, the plane-wave pseudopotential calculations with the generalized gradient approximation (GGA) of Perdew-Burke-Ernzerhof (PBE) have been carried out using the Materials Studio 7.0 Package6162How to cite this article: Li, M. et al. Superior adsorption and photoinduced carries transfer behaviors of dandelion-shaped Bi2S3@MoS2: experiments and theory. Sci. Rep.7, 42484; doi: 10.1038/srep42484 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


The purpose of this study was to investigate the effect of hippotherapy and electroencephalography (EEG) neurofeedback on brain function and blood brain-derived neurotrophic factor (BDNF) level in children with attention-deficit or/and hyperactivity disorder (ADHD).n = 8) and a 2-time hippotherapy group . All the participants attended 8 weeks of hippotherapy program in the primary training, and then 7 children with ADHD attended 8 weeks of hippotherapy program combined with neurofeedback training in the secondary training. Blood BDNF levels were measured, and functional magnetic resonance imaging (fMRI) was performed. The EEG neurofeedback training program was used to train and measure psychological factors.Sixteen children with ADHD participated in this study and were randomly divided into 2 groups, a 1-time hippotherapy group . fMRI results showed that the left thalamus activity in both groups had a decreased tendency and a significantly lower change in W2G than in W1G (p < 0.05).The combined effect of hippotherapy and neurofeedback on BDNF level showed a decreased tendency in W1G . However, the BDNF level of W2G showed an increased tendency . Moreover, combined training showed a significant group x repetition interaction in W1G (pretraining, 1436.57 ± 368.76 pg/ml; posttraining, 1525.23 ± 346.22 pg/ml; F = 3.870, This study confirmed a significant increase in blood BDNF level after combined training, which may induce brain function improvement in children with ADHD. ADHD occurs in school-aged boys and girls, and is characterized by difficulty in social relationships and lower study achievement3. In a previous report, Korean children showed a higher ADHD incidence (3–20%)4 than children in the United States (3–8%)5 and Japan (7–12%)6.Attention-deficit or/and hyperactivity disorder (ADHD) has been known to usually evoke hyperactivity, impulsiveness, and aggression, and the incidence of ADHD higher in boys than in girls8. The brain-derived neurotrophic factor (BDNF) plays a key role in nerve cell division of dopamine9. Moreover, dopamine is involved in the regulation of the posterior attention system (PAS) related to action, memory, judgment, plan, and response. Meanwhile, norepinephrine is involved in the regulation of the anterior attention system (AAS) related to stimulus selection and choice, and attention distribution, maintenance, and change. Accordingly, malfunction of PAS and AAS may cause severe problems in execution functions such as personal relationships and coordination11. Malfunction in PAS and AAS activates slow brainwaves via quantitative electroencephalography (QEEG). Therefore, activating the theta-to-beta wave ratio would be useful to improve physiological symptoms in children with ADHD14. In addition, children with ADHD need to have medical treatment and management as early as possible because only 20% of these children recover as they age and most continue to have ADHD through their adulthood8.The physiological mechanism of ADHD shows that lower activity levels of dopamine D4 receptor gene and norepinephrine mainly induce functional reduction in the right and dorsal frontal lobe of the brain16. Thus, exercise therapy for children with ADHD has been suggested to activate brain function17. A previous study reported that exercise therapy and/or physical activity combined with cognitive function training for children with ADHD positively affected ADHD18. Horseback riding or hippotherapy has been a useful therapy for enhancing neuromuscular function since the 1970s in Europe and the United States19. Use of animals such as horses in therapy would be effective for positively changing psychological factors, social positioning act, quality of life, and movement function in children with ADHD21. Horseback riding has been known to be effective as a high-intensity physical activity (>4 METs)22. Thus, hippotherapy would apply to functionally improving behavioral modification and psychological factors in children with ADHD. In addition, previous studies confirmed that above-moderate-intensity hippotherapy was positively effective for functional improvement in children with ADHD23.Methylphenidate and amphetamine are drugs used for the treatment of ADHD; however, approximately 20% of these medicines have been reported to evoke side effects such as hypertension, sleep disorder, and mood disorder, and just temporarily reduce ADHD symptoms24 and can generally be applied as a treatment method for enhancing brain function in children with ADHD because it is programmed for brain function improvement25. Recent Internet technology uses a server-based long-distance learning system that enables patients to easily use the EEG neurofeedback training program and maximizes patients’ participation at home. In addition, this would be practically applicable for better therapeutic results in children with ADHD. Therefore, the purpose of this study was to investigate the combined effect of hippotherapy and EEG neurofeedback on brain function and blood BDNF level in children with ADHD.EEG neurofeedback training has been defined as a comprehensive training system by changing the brain function of children with ADHDThe study participants were patients with ADHD who were recruited from the pediatric psychiatry departments of G university and C university hospitals. Parents, physicians, and children with ADHD understood the study purpose and signed the study consent form. Previous medical history information was collected, and a psychological medical examination was conducted for calculating the attention quotient (AQ) for selecting the study patients. To examine the changes in serum BDNF level and brain function in children with ADHD followed by the primary training, 16 participants were divided into the “one time per week” group  and the “two times per week” group  during the 8-week training period. The secondary training was designed for W1G and combined with neurofeedback training, with 7 children with ADHD as participants .Primary training was conducted to investigate the changes in serum BDNF level and brain function in the children with ADHD, followed by the 1- and 2-time hippotherapy programs during the 8-week training period. The participants in W1G and W2G performed the walk and sitting trot training during the first 4 weeks and the walk and sitting trot training without a stirrup iron after 5 weeks of training .In W1G, training was combined with neurofeedback training. To examine the changes in serum BDNF level and brain function, the prefrontal lobe of the brain was trained using the NH neurofeedback system through the sequential bipolar montage for 30 minutes. The brain wave range was set at 45 Hz .Blood BDNF level was measured at baseline and after the hippotherapy and combination trainings. Blood BDNF level was analyzed using human enzyme-linked immunosorbent assay kits (AB Frontier). Blood was collected from the forearm venous vein, and the collected blood was stored in serum tubes. It was centrifuged at 1000×g (relative centrifuged force) for 15 minutes, and 0.1 ㎖ of separated serum was analyzed using the Microplate model 680 . Then, the blood sample was analyzed using a human BDNF kit, followed by the ELISA method. The BDNF level was calculated by measuring optical density.To measure brain function, functional magnetic resonance imaging (fMRI) was used. A 3.0-Tesla GE MR scanner  was used to check the anatomical structure of the brain. T-1 imaging as the 3-D spoiled gradient echo pulse sequence (SPGR) was also used to scan 240 sagittal images of the brain. A T-2 image scan was used to check the brain structure. A fMRI scan was conducted using the quadrature-type head coil, and MR sequence was shown .EEG was used to test brain waves and Neuro H. Neurofeedback System was used. Neuro H. System is a portable 2 Channel System digital brain wave measuring instrument and it measures the both frontal robes by using the Sequential Bipolar Montage. Brain Quotient (BQ) program was used to test brain waves.Comprehensive attention test (CAT) is a standardized attention test that includes 6 subcategories, namely visual simple selection attention capacity, auditory simple selection attention capacity, suppression continuous attention capacity, interference selection attention capacity, division attention capacity, and job memory capacity. CAT is a computer-based program that takes 30–40 minutes to complete and calculates the tester’s score. CAT can report emotion and behavioral scores of children with ADHD. This measurement was used only in the secondary training.Descriptive statistics were calculated using the means and the standard deviations from the collected data. The two-way mixed analysis of variance (group × repetition) was used to test the changes in serum BDNF level after the primary training. In addition, to examine the fMRI results for brain function changes, a paired-sample T test was conducted by converting image data into numeric data and to compare the difference between the baseline and after the 8-week training. To confirm the efficacy of the secondary training, a paired-sample T test was conducted. The significance level in all the tests was set at p < 0.05.The blood BDNF level change after hippotherapy based on hippotherapy frequency showed a decreased tendency in W1G from before (1766.03 ± 362.54 pg/ml) to after training (1630.65 ± 276.70 pg/ml). By contrast, the blood BDNF level in W2G showed an increased tendency from before (1968.28 ± 429.08 pg/ml) to after training (1976.28 ± 425.35 pg/ml), which showed a significant interaction  changes after the 8-week combined training with hippotherapy and neurofeedback did not induce significant changes in basic rhythm (Left·Right), self-control index, attention index (Left·Right), activation index (Left·Right), emotion index, anti-stress index (Left·Right), left and right brain balance, and brain index. This might have resulted from taking medication during the 8-week training, and emotional expressions seem to be absent at the pretest .As shown in As shown in 8 and are expected to have increased activities in the right and dorsal frontal lobes. This study proved that the left thalamus activity in W2G was significantly higher than that in W1G. However, participation twice per week in the hippotherapy program may practically cause a cost-effectiveness problem; thus, children with ADHD are recommended to participate once per week in the hippotherapy program combined with neurofeedback training because neurofeedback training has a comparably lower cost and is as fun and interesting as a game for children. In this study, we found a significant job memory increase of the left bilateral middle frontal cortex, right bilateral middle frontal cortex, and left precentral cortex after by hippotherapy and neurofeedback training. Moreover, this study confirmed that the decision-making area of the brain activity was increased during task performance.This study suggests that hippotherapy might induce neurotransmitter activation in children with ADHD because they usually have lower neurotransmitter activation26 also suggested that regular physical activity might induce HDAC regulation and thus blood BDNF activation. These study results showed that the blood BDNF level in W1G combined with neurofeedback training was significantly increased in comparison with that in W2G. This study result may have been induced by the HDAC regulation caused by the muscle contraction after hippotherapy participation and brain function changes at the cell level after neurofeedback training25.This study also suggests that skeletal muscle improvement in children with ADHD throughout horseback riding might regulate histone deacetylase (HDAC) from skeletal muscles. McGee et al.27 insisted on a negative association between dietary energy intake and blood BDNF level, which supports our finding. Our study results showed a significant increase in blood BDNF level after combined training, which may induce brain function improvement in children with ADHD. No previous study related to the present study has been conducted; thus, we cannot clearly compare our study results to previous study results. However, we can expect a positive combined effect of hippotherapy and neurofeedback training because this study found significant cerebral cortex activity changes. Moreover, the present study results showed no significant difference in serum BDNF level between the primary and secondary trainings. However, this would be considered as a crucial factor for understanding the overall study results. We can assume that the sensitivity of serum BDNF concentration was affected by the analytical method by removing plasma protein such as fibrinogen, which resulted in a decreased BDNF concentration and was affected by the muscle contraction in children with ADHD before blood drawing. In relation with this assumption, Cho et al.28 reported that muscle contraction could induce platelet activation and affect changes in serum BDNF level changes. To clarify this assumption, an adjusted method for examining serum BDNF level changes, followed by the physical activity level, in children with ADHD should be considered in future intervention studies.Increased left thalamus activity in W2G may be effective in suppressing caloric intake and might be expected to be effective for reducing oversupplied caloric intake in children with ADHD. This study did not investigate the hyperactivity pattern in children with ADHD and may not clearly present behavioral pattern changes via the hippotherapy program combined with neurofeedback training. Nevertheless, the blood BDNF changes after combined training showed a possibility to contribute to behavioral pattern changes throughout the hippotherapy program combined with neurofeedback training. Mattson (2010)This study has two limitations. First, the ADHD level of each participant might be inconsistent, which might have negatively affected the study results. Second, the progress of each participant in hippotherapy differed because of the different levels of learning ability. This might have caused a variation in exercise intensity, although the study set the same exercise intensity. We recommend that future studies consider consistency of ADHD level and unified exercise intensity application for better understanding of the effects of hippotherapy and neurofeedback training on children with ADHD.Enhanced brain function was observed in the children with ADHD as their participation frequency in hippotherapy increased. However, a cost-effectiveness problem may be evoked as hippotherapy participation frequency is increased. Therefore, participation once per week in the hippotherapy program combined with neurofeedback training would optimize cost-effectiveness and brain function enhancement in comparison with participation twice per week in the hippotherapy program. This study suggests that hippotherapy combined with various psychological interventions would be useful for improving brain function in children with ADHD.