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.
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.
Spent mushroom substrate (SMS) is the by-products of mushroom production, which is mainly composed of disintegrated lignocellulosic biomass, mushroom mycelia and some minerals. The huge output and ...the lack of effective utilization methods make SMS becoming a serious environmental problem. In order to improve the application of SMS and SMS derived biochar (SBC), composted SMS (CSMS), SBC, combined plant growth-promoting rhizobacteria (PGPR,
BUABN-01 and
BUAYN-122) and SBC immobilized PGPR (BCP) were applied in the lettuce seedling. Seven substrate treatments were used, including (1) CK, commercial control; (2) T1, CSMS based blank control; (3) T2, T1 with combined PGPR (9:1, v/v); (4) T3, T1 with SBC (19:1, v/v); (5) T4, T1 with SBC (9:1, v/v); (6) T5, T1 with BCP (19:1, v/v); (7) T6, T1 with BCP (9:1, v/v). The physicochemical properties of substrate, agronomic and physicochemical properties of lettuce and rhizospheric bacterial and fungal communities were investigated. The addition of SBC and BCP significantly (
< 0.05) improved the total nitrogen and available potassium content. The 5% (v/v) BCP addiction treatment (T5) represented the highest fresh weight of aboveground and underground, leave number, chlorophyll content and leaf anthocyanin content, and the lowest root malondialdehyde content. Moreover, high throughput sequencing revealed that the biochar immobilization enhanced the adaptability of PGPR. The addition of PGPR, SBC and BCP significantly enriched the unique bacterial biomarkers. The co-occurrence network analysis revealed that 5% BCP greatly increased the network complexity of rhizospheric microorganisms and improved the correlations of the two PGPR with other microorganisms. Furthermore, microbial functional prediction indicated that BCP enhanced the nutrient transport of rhizospheric microorganisms. This study showed the BCP can increase the agronomic properties of lettuce and improve the rhizospheric microbial community.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Nitrilase-catalyzed regioselective hydrolysis of 1-cyanocyclohexaneacetonitrile (1-CHAN) is a green and efficient approach for the preparation of 1-cyanocyclohexaneacetic acid (1-CHAA), a key ...precursor for the synthesis of gabapentin. Here, a mesoporous biosilica particles prepared by the ethyleneamine-mediated silicification have been used as carrier for the encapsulation of nitrilase from Acidovorax facilis (NitA). The silica-encapsulated NitA (NitA@silica) with triethylenetetramine as an initiator showed the highest immobilization efficiency (98.3%) and specific activity (672.6 U/g). Both free and encapsulated NitA were optimally active at 40 °C and pH 7.0, however, the encapsulated enzyme exhibited wider optimum temperature range, and enhanced thermal stability compared with the free enzyme. The kinetic parameters Km and Vmax for free and encapsulated NitA were calculated to be 141 mM and 9.97 mM min−1, and 280 mM and 9.02 mM min−1, respectively. The encapsulated NitA showed good reusability and retained about 94.2% of its initial activity even after 16 cycles of reaction. Also, the storage experiments revealed high activity maintenance of encapsulated NitA after 17-day storage at 4 °C. A preparative scale regioselective hydrolysis of 1-CHAN to 1-CHAA with encapsulated NitA as biocatalyst was carried out in a 2 L stirred bioreactor. The concentration of 1-CHAA reached 152 g/L after 8 h reaction and the conversion was 90.9%. These results showed that the encapsulation of NitA in ethyleneamine-mediated biosilica is an efficient and simple way for preparation of stable nitrilase and have a great potential for application in enzymatic production of carboxylic acids.
•A novel method of nitrilase encapsulation on ethyleneamine-mediated biosilica particles is proposed.•Biosilica-encapsulated nitrilase exhibited extremely high immobilization efficiency and specific activity.•The performance of the encapsulated nitrilase was evaluated by the synthesis of 1-cyanocyclohexaneacetic acid.•The encapsulated nitrilase can keep its catalytic activity after being reused sixteen times.
•A new model for creep-recovery of NSC and HSC were proposed.•A creep recovery test of HSC under 0.3 and 0.5 stress level was presented.•The recoverable creep of HSC was founded smaller than that of ...NSC.
The creep-recovery behavior of both normal and high strength concrete (HSC) under various load conditions has not been studied thoroughly. Although the use of HSC is long-established, rational creep-recovery prediction of HSC is still unavailable since current study just regards recovery deformation as a secondary result of creep experiments. In this paper, a new prediction model for creep-recovery of normal strength concrete (NSC) with considering the influence of stress level and load history was proposed at first. Then, a model for HSC creep-recovery was established according to creep-recovery data of NSC and HSC in literatures and the influence of compressive strength of concrete. To validate the HSC model, an experimental study of the creep behavior of C80 concrete was conducted. Creep and residual strain after unloading of specimens at various compression stress levels (30% and 50% of the compression strength) were compared with the HSC creep-recovery model. Although the HSC model tends to underestimate the first 7days’ creep-recovery value, the results show high overall prediction accuracy. Moreover, parametric analysis results indicate that the recoverable creep of HSC reduces significantly than that of NSC. The effect becomes stronger with the increase of loading age and weaker with a prolongation of load duration.
Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on ...angiography (stenosis < 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA.
A total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR−). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%–75% of peak heart rate) on a bicycle or treadmill.
After one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR− group (P < 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P < 0.05) and MACE (log-rank P < 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio HR = 0.483; 95% confidence interval CI, 0.279–0.818; P < 0.01) and MACE (HR = 0.574; 95% CI, 0.403–0.827; P < 0.001).
A long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.
•Patients with myocardial infarction with nonobstructive coronary arteries are common.•Exercise-based cardiac rehabilitation results in superior physical health.•Exercise training reduces all-cause mortality and cardiovascular events.
•A novel quantitative measure reflecting functional connectivity asymmetry of brain was employed.•The largest resting-state fMRI dataset of major depressive disorder in China was used.•Many brain ...networks contribute to broad clinical pathophysiology of MDD.•A lateralized, efficient and economical brain information processing system is disrupted in MDD.
: 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.
: 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).
: 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.
: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results.
: 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.
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.
•The present study is the first to investigate the GMV and GMD changes of the regional brain in MDD patients with GI symptoms through multicenter clinical data, based on the VBM of structural MRI.•The study found MDD patients with GI symptoms have more severe depressive symptoms.•The study pointed out that the dysfunction of CNS may be one of the important pathophysiologic mechanisms causing GI symptoms in MDD patients.
•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.
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.
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.
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.
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.
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