Summary
Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with ...little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a “hub” in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal‐subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.
Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ...ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12‐month‐old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H‐MRS). The results showed that N‐acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg‐NSC mice compared with the Tg‐PBS and Tg‐AD mice 10 weeks after NSCs transplantation. NSC‐induced an increase in expression of synaptophysin and postsynaptic protein‐95, and the number of neurons with normal synapses was significantly increased in Tg‐NSC mice. More doublecortin‐, BrdU/NeuN‐ and Nestin‐positive neurons were observed in the hippocampal DG and SVZ of the Tg‐NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H‐MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H‐MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.
Background Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion ...of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.
Abstract
The large-span pipe bridge is widely applied to long-distance water diversion projects because of its large crossing capacity, strong integrity, and adaptability to complex terrain. However, ...under the action of an earthquake, the pipe bridge will often produce large displacement, which can lead to large deformation of the whole system and damage to the pipe bridge structure. At present, there are relatively few studies on the seismic response of such pipe bridges for water diversion, and even there is also a lack of special design specifications for pipe bridges. Combined with the construction practice of the KLH long-span pipe bridge, based on the finite element analysis, the seismic response characteristics and dynamic stabilization of the long-span pipe bridge are analyzed, so the structure optimization scheme is proposed for the key parts of the bridge. The research results can provide new ideas for the seismic design of the long-span pipe bridge.
Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. ...Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD.
A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD.
A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus.
Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.
► We quantitatively reviewed VBM studies in patients with MDD. ► We performed a modified ALE meta-analysis hybridized with GSMA. ► Twenty studies comparing gray matter between patients and controls were included. ► Gray matter reductions in MDD were found in bilateral ACC and right hippocampus.
Most studies of resting-state functional magnetic resonance imaging (fMRI) have applied the temporal correlation in the time courses to investigate the functional connectivity between brain regions. ...Alternatively, the power of low frequency fluctuation (LFF) may also be used as a biomarker to assess spontaneous activity. The purpose of the current study is to evaluate whether the amplitude of the LFF (ALFF) relates to cerebral physiological states. Ten healthy subjects underwent four resting-state fMRI scanning sessions, two for eyes-open (EO) and two for eyes-closed (EC) conditions, with two sets of parameters (TR=400 ms and 2 s, respectively). After data preprocessing, ALFF was obtained by calculating the square root of the power spectrum in the frequency range of 0.01–0.08 Hz. Our results showed that the ALFF in EO was significantly higher than that in EC (P<0.05, corrected) in the bilateral visual cortices. Furthermore, the ALFF in EO was significantly reduced in the right paracentral lobule (PCL) than in EC (P<0.05, corrected). Region of interest (ROI) analysis showed that the ALFF differences between EO and EC were consistent for each subject. In contrast, no significant ALFF differences were found between EO and EC (P<0.381) in the posterior cingulate cortex. All these results agree well with previous studies comparing EO and EC states. Our finding of the distinct ALFF difference between EO and EC in the visual cortex implies that the ALFF may be a novel biomarker for physiological states of the brain.
Mutant KRAS and BRAF are associated with primary EGFR inhibitor resistance in colorectal cancer (CRC). However, other biomarkers that could predict EGFR inhibitor resistance remain elusive. In the ...present study, immunoblotting and cell proliferation results revealed that yes‑associated protein (YAP), a downstream effector of the Hippo pathway, was positively associated with primary cetuximab resistance in CRC cells. YAP knockdown enhanced the cytotoxicity of cetuximab in CRC cells. Simvastatin, a 3‑hydroxy‑3‑methylglutaryl‑coenzyme A (HMG‑CoA) reductase inhibitor of the mevalonate pathway that inhibits YAP bioactivity through nuclear translocation and total YAP expression, increased the cytotoxicity of EGFR inhibitors (cetuximab and gefitinib) against CRC cells. The combination of simvastatin and EGFR inhibitors inhibited YAP and EGFR signaling more markedly than each agent alone. Adding back geranylgeranyl pyrophosphate (GGPP), a key product of the mevalonate pathway, reversed the YAP bioactivity inhibition induced by simvastatin and the cell proliferation inhibition induced by the combination of simvastatin and EGFR inhibitors. Collectively, these results revealed that YAP may be useful in identifying cetuximab resistance in CRC and indicated that targeting of both YAP and EGFR signals may present a promising therapeutic approach for CRC.
Functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD) have revealed cortical-limbic-subcortical dysfunctions during working memory (WM) processing, but the results ...are inconsistent and it is unclear to what extent these findings are influenced by demographic, clinical characteristics and task performance of patients. The present study conducted a quantitative coordinate-based meta-analysis of fMRI data to investigate the hypothesized dysfunction in the neural correlates during WM processing in MDD.
A systematic research was conducted for fMRI studies during WM processing comparing MDD patients with healthy controls (HC). Meta-analysis was performed using effect size signed differential mapping (ES-SDM). Meta-regression analyses with age, sex and medication as factors were performed in MDD group.
Functional MRI data of 160 MDD patients and 203 HC from 13 WM experiments across 11 studies were included in this meta-analysis. In the pooled meta-analysis of all included studies, significant increased activation during WM in the left lateral prefrontal cortex, left precentral gyrus, left insula, right superior temporal and right supramarginal areas, and significant decreased activity in the right precentral gyrus, right precuneus and right insula were observed in MDD compared with controls. In the subgroup analysis of the studies with matched task performance, MDD subgroup showed hyperactivation only in the left prefrontal cortex and hypoactivation in the regions similar to the pooled analysis. The meta-regression with age, sex and medication showed no significance in MDD group.
Regardless of differences in task performance between groups, patients with MDD showed consistent functional abnormalities in the cortical-limbic-subcortical circuitry during WM processing. Distinct patterns of neural engagement may reflect compensatory neural strategies to potential dysfunction in MDD.
•A meta-analysis quantitatively reviewed fMRI studies during working memory in MDD.•Eleven studies comparing the brain activation between groups were included.•Activation differences occurred in cortical-limbic-subcortical circuitry in MDD.•MDD subgroup with equal task performance involved fewer brain regions.
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