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Background The subgenual anterior cingulate cortex (sgACC) appears to play a central role in the pathophysiology of major depressive disorder (MDD). To wit, its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) has been shown to be related to treatment outcomes with transcranial magnetic stimulation (TMS) treatment outcomes. Nevertheless, previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power of prior work.Methods Here, leveraging a large multi-site sample (1660 MDD patients vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT), we systematically delineated case-control difference maps of sgACC FC and examined their clinical relevance to previously identified TMS targets. We also investigated case-control FC difference maps of left DLPFC sub-fields.Results In MDD patients we found significantly increased FC between sgACC and thalamus and reduced FC to a broad array of brain regions, including somatosensory area, occipital lobe, medial and lateral temporal lobe, and insular cortex, when global signal regression (GSR) was not implemented. Intriguingly, we found enhanced left DLPFC-sgACC FC in MDD patients when GSR was performed. We leveraged an prior independent sample to explore the possible relationship between the case-control differences regarding sgACC’s FC profiles and the treatment out comes of TMS. In sites in which open TMS treatment was administered, case-control differences in sgACC FC, with GSR, were related to clinical improvement. Next we tested whether the position of peak of the FC maps (previously identified TMS target) could be altered in MDD patients as compred with healthy controls (HC)s. We found the optimized TMS target differed in MDD patients. Several DLPFC sub-fields yielded case-control differences in whole-brain FC maps.Conclusion In summary, we reliably delineated MDD-related abnormalities of sgACC FC profiles in a large sample. GSR was essential in applying case-control difference maps to identify optimized TMS targets. Our results highlight the functional heterogeneity of the left DLPFC and of precise TMS targets therein.

Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations.In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns.As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs.We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Objective Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. Methods In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. Results Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Background : Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. Methods : Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). Results : Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. Limitations : Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. Conclusions : Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

The multilayer dynamic network model has been proposed as an effective method to understand how the brain functions dynamically. Specially, derived from the definition of clustering coefficient in static networks, the temporal clustering coefficient provides a direct measure of topological stability of dynamic brain networks and shows potential in predicting altered brain functions in both normal and pathological conditions. However, test–retest reliability and demographic-related effects on this measure remain to be evaluated. Using a publicly available dataset from the Human Connectome Project consisting of 337 young healthy adults (157 males/180 females; 22 to 37 years old), the present study investigated: (1) the test-retest reliability of temporal clustering coefficient across four repeated resting-state functional magnetic resonance imaging scans as measured by intraclass correlation coefficient (ICC); and (2) sex- and age-related effects on temporal clustering coefficient. The results showed that (1) the temporal clustering coefficient had overall moderate test-retest reliability (ICC > 0.40 over a wide range of densities) at both global and subnetwork levels; (2) female subjects showed significantly higher temporal clustering coefficient than males at both global and subnetwork levels, in particular within the default-mode and subcortical regions; (3) temporal clustering coefficient of the subcortical subnetwork was negatively correlated with age in young adults. Our findings suggest that temporal clustering coefficient is a reliable and reproducible approach for the identification of individual differences in brain function, and provide evidence for sex and age effects on human brain dynamic connectome.

Significance Functional connectivity within the default mode network in patients with major depressive disorder has been frequently reported to be abnormal but with contradicting directions in previous studies with small sample sizes. In creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments., Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

This paper uses literature and comparative methods to research the evolution characteristics of women's views on sports at three different stages in modern China. The major findings are as follows: (1) The modern Chinese women's views on sports has undergone three different stages that evolve and interact mutually, from "entertainment" to "self-emancipation", from "protecting the country by strengthening people" to "women's fitness" and from "gender difference" to "gender equality". (2) China's modern views on sports at three different stages present distinctive historic features—namely high competitiveness, modernization and diversity. (3) The evolution characteristics of women's views on sports at three different stages in modern China reflect women's attitudes and inclination towards sports.

Background: The COVID-19 pandemic has increased perceived psychological stress among adolescents, who experienced the lockdown period with their family. We investigated the role of family function (FF) in the interrelation between perceived stress (PS), psychotic-like experiences (PLEs) and suicidal ideation (SI) during this pandemic. Methods: 4807 adolescents completed this cross-sectional survey between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with Perceived stress scale (PSS-10), PLEs with the 8-item version of Community Assessment of Psychic Experiences (CAPE), SI with the suicidal item from the Mental Health Inventory of Middle School Students (MMHI-60), and FF with Family APGAR scale. Spearman’s correlation, mediation and moderated mediation analysis were utilized as statistical methods, adjusting for age and sex. Findings: Adolescents with high PS had higher PLEs (r = 0·51) as well as SI (r = 0·48); higher PLEs were related to more SI (r = 0·46). FF was lower in adolescents with higher PS (r = -0·34), PLEs (r = -0·29) and SI (r = -0·32) [All above p < 0·0001]. Moreover, PS had an indirect influence on SI mediated via increased PLEs (indirect effect = 0·029). Higher FF significantly attenuated the effect of PS on PLEs (effect = -0·012), PS on SI (effect = -0·006), but did not reduce the effect of PLEs on SI. Interpretation: Our findings indicate that interventions to improve family function could reduce the stress-induced psychotic-like experiences and suicidal ideation during enforced social isolation. Funding Statement: This work was supported by the China Precision Medicine Initiative (2016YFC0906300 to ZL), the National Natural Science Foundation of China (82071506 to ZL). LP acknowledges support from the Tanna Schulich Chair of Neuroscience and Mental Health. Declaration of Interests: LP reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work. All other authors report no relevant conflicts. Ethics Approval Statement: Our study was approved by the Ethics Committees of the Second Xiangya Hospital of Central South University.

Highlights • Two subtypes with distinct default mode network profiles exist in major depression. • Subtypes of major depression are robust in validation datasets across brain atlases. • Hyper- & hypo-connectivity DMN subgroups have comparable clinical symptom variables. • Future studies should examine whether two subtypes have differing treatment response., Background Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. Methods The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. Results Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. Conclusions Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10−3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure.Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms.There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P 0.01, voxel-P 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P 0.01, voxel-P 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P 0.01, voxel-P 0.001). While these changed brain areas had significantly association with GI symptoms (P 0.001), they were not correlated with depressive symptoms (P 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe.MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Fencing originated from Europe in the Middle Ages, which was the product of different factors' interaction in ancient society. Since the modern Olympic Games, fencing has exerted a far-reaching influence on all aspects of society. This paper studies the value of fencing from the Olympic perspective. The value of fencing is mainly manifested in four aspects: the competitive value of fencing, the educational value of fencing, the cultural value of fencing and the economic value of fencing. These four aspects are interrelated to each other, interdependent on each other and interacting with each other. The purpose of this study is to further popularize fencing and promote its development.

Background: Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Methods: The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. Outcomes: We found decreased instead of increased DMN FC in MDD compared to NCs. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration or severity. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. Interpretation: We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. All the R-fMRI indices have been made publicly available via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal MDD studies and to other psychiatric disorders. Funding Statement: This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031 and 81371488), the Hundred Talents Program of the Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152 and Z171100000117016), Department of Science and Technology, Zhejiang Province (2015C03037). Declaration of Interests: All the authors declare no competing financial interests. Ethics Approval Statement: All contributed data were from studies approved by local Institutional Review Boards. Data submitted to the consortium were fully deidentified and anonymized.

The neuroexcitotoxic nonprotein amino acid, beta-N-oxalo-L-alpha,beta-diaminopropionic acid (beta-N-ODAP) was found in Panax species such as Panax ginseng 'C.A. Meyer' (cultivated in Northeastern China), Panax quinquefolius (L), Panax notoginseng 'F.H. Chen' (cultivated in Southwestern China), Korean red ginseng and Jilin (China) red ginseng. beta-N-ODAP was verified to be a natural substance, and its isomer alpha-N-oxalo-L-alpha,beta-diaminopropionic acid (alpha-N-ODAP) is very likely an artifact generated during the separation process. The interconversion between beta-N-ODAP and alpha-N-ODAP was observed. Results showed that both beta-N-ODAP and alpha-N-ODAP can easily be converted into their isomers at higher temperature or in acidic and basic solution. Their interconversion equilibrium constant and rate constants were obtained. Upon extensive study and a good understanding of the interconversion, accurate physical constants and spectroscopic data such as MS, 1H NMR, 13C NMR and UV were obtained.

At different thermodynamic temperatures (between 0.01 and 4000 K), the relaxation properties of three kinds of graphene nanoribbons with different aspect ratios are simulated by molecular dynamics method based on Tersoff-Brenner and AIREBO potential functions separately. Then we compare the energy curves and surface morphologies of nanoribbon relaxation with two kinds of potential functions, and study the dynamic equilibrium process of the graphene nanoribbons during their relaxation simulation. The simulation results show that the single layer graphene nanoribbon is not of a perfect planar structure and that a certain degree of fluctuations and folds occur at the edges and inside of nanoribbons, which are consistent with the existing experimental results; the surface fluctuation level of graphene nanoribbons decreases with the reduction of the aspect ratio, and the system kinetic energy has a dramatic influence on the relaxation deformation of the graphene nanoribbons at different temperatures, which indicates that the higher the system temperature, the greater the deformation is. Curl phenomenon could appear even on the surface of the nanoribbon with a high aspect ratio at a certain temperature. Finally, the simulations of graphen molecular dynamics by using the Tersoff-Brenner and AIREBO potential are deeply analyzed.