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Freshwater mussels are essential for the integrity of freshwater ecosystems but numbers of these organisms are declining rapidly at regional and global scales. The phylogenetic and biogeographic aspects of the rich unionoid fauna of the Indo-Burma region are becoming increasingly well understood. Guangxi is part of the Chinese portion of the Indo-Burma biodiversity hotspot but regional studies of the freshwater mussel diversity are scarce. In this study, we report a new genus and species of freshwater mussel from Guangxi, China. Genetic datasets including three genes (COI, 16S rRNA and 28S rRNA) and complete maternal mitogenomes were compiled to infer the phylogenetic history of the group. Molecular phylogenetic analyses showed that the new species formed a monophyletic group and was closely related to Obovalis and Ptychorhynchus in the tribe Gonideini of the subfamily Gonideinae. Morphological and molecular evidence supported that these specimens represent an undescribed genus and species that we describe as Postolata guangxiensis gen. nov., sp. nov. The discovery of this new taxon adds to the known level of endemism of freshwater mussels in Guangxi and a detailed survey of uncharted areas should reveal new diversity in the future. We also suggest that complete mitogenomes or even genome-scale nuclear data should be used for phylogenetic reconstructions when proposing major taxonomic changes. ZooBank: urn:lsid:zoobank.org:pub:76FC5A1D-7507-4F26-A12C-EC08AB333274

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.

Cable-supported photovoltaic (PV) modules have been proposed to replace traditional beam-supported PV modules. The new system uses suspension cables to bear the loads of the PV modules and therefore has the characteristics of a long span, light weight, strong load capacity, and adaptability to complex terrains. It provides an excellent supplement to traditional structures in special sites such as sewage treatment plants, highways, farms, fishponds, and roofs with poor load-bearing conditions. However, most of the traditional cable-supported PV systems use only two cables to support the PV modules. The settlement of the support cables due to self-weight of PV modules always reduces their power generation efficiency. Therefore, it is necessary to make a reasonable design to flatten the structures. Recently, the authors (He et al., 2020) proposed a new cable-supported PV system using three cables and four triangle brackets to form an inverted arch to reduce the vertical displacement of the PV modules. In this study, the structural characteristics of the new PV system with a span of 30 m are numerically investigated in terms of mode shapes, modal frequency, and nonlinear structural stiffness through using the finite element method. The increase of torsion stiffness when the torsion displacement rises benefits the stability of the new PV system. The load bearing capacity of the PV system is discussed under self-weight, static wind load, snow load, and their combination. The influences of row spacing, tilt angle, initial cable force, and cable diameter on the structural characteristics are further studied. The results verify that the new system has a strong load capacity and potential for wide application.

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.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production., The expression of ME2 was significantly elevated in HCC tissues.ME2 promotes HCC progression by increasing triglyceride production.

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 propeller cavitation not only affects the propulsive efficiency of a ship but also can cause vibration and noise. Accurate predictions of propeller cavitation are crucial at the design stage. This paper investigates the feasibility of the Reynolds-averaged Navier–Stokes (RANS) method in predicting propeller cavitation in behind-hull conditions, focusing on four aspects: (i) grid sensitivity; (ii) the time step effect; (iii) the turbulence model effect; and (iv) ability to rank two slightly different propellers. The Schnerr-Sauer model is adopted as the cavitation model. A model test is conducted to validate the numerical results. Good agreement on the cavitation pattern is obtained between the model test and computational fluid dynamics. Two propellers are computed, which have similar geometry but slightly different pitch ratios. The results show that RANS is capable of correctly differentiating the cavitation patterns between the two propellers in terms of the occurrence of face cavitation and the extent of sheet cavitation; moreover, time step size is found to slightly affect sheet cavitation and has a significant impact on the survival of the tip vortex cavitation. It is also observed that grid refinement is crucial for capturing tip vortex cavitation and the two-equation turbulence models used – realizable k-ε and shear stress transport (SST) k-ω – yield similar cavitation results.

Background. Thoracic surgery is one of the most painful surgical steps. An important tool for managing postoperative pain is effective postoperative analgesia. This research aimed at comparing the analgesic roles of three new fascial block techniques in the postoperative period after video-helped thoracoscopic operation (VATS). Methods. We randomly allocated ninety patients into three teams experiencing ultrasound-directed serratus plane block, erector spinae plane block, and the rhomboid intercostal block, respectively. 0.4% ropivacaine of 20 mL was received by all groups. Outcomes. At 0–12 hours, sufentanil consumption was significantly lower in the RIB (35.2 ± 3.3 mg) and ESP (35.4 ± 2.8 mg) groups than that in the SAB (43.3 ± 2.7 mg) group P < 0.001 , and no obvious diversity in sufentanil consumption was shown between the RIB and ESP groups P = 0.813 . At 12–24 hours, sufentanil consumption was greatly lower in the RIB and ESP groups than that in the SAB group P < 0.001 , and no great diversity in sufentanil consumption was found between the RIB and ESP groups P = 0.589 . No great diversity in sufentanil consumption was shown between the RIB (50.4 ± 1.4 mg), ESP (50.4 ± 1.5 mg), and SAB (51.0 ± 1.7 mg) groups at 24–48 hours P = 0.192 . At 6, 12, 18, and 24 hours, the postoperative dynamic NRS scores were significantly lower in the RIB and ESP groups than in the SAB group ( P < 0.05 for all contrasts). Nevertheless, no great diversity was observed in postoperative pain marks at 0.5, 1, 3, 6, 12, 18, 24, 36, and 48 hours after the surgery across the three groups. No statistical diversity was found in the postoperative NRS mark between groups RIB and ESP within 48 hours after surgery in case of active patients ( P < 0.05 for all contrasts). At 24 hours after surgery, a significant difference in IL-1β and IL-6 inflammatory factor concentrations was found between RIB and ESP compared with SAB block ( P < 0.05 for all contrasts). However, no great diversities were observed in IL-1β, and IL-6 inflammatory factor concentrations between RIB, ESP, and SAB at 24 hours preoperatively and at 48 hours postoperatively ( P < 0.05 for all comparisons). Conclusion. The dosage of sufentanil can be effectively reduced by ultrasound-directed rhomboid intercostal block and erector spinae plane block within 24 hours after VATS surgery, and pain can be relieved effectively within 24 hours by comparing with serratus plane block.

Pleurotus pulmonarius, a member of the Pleurotaceae family in Basidiomycota, is an edible, economically important mushroom in most Asian countries. In this study, the complete mitochondrial genomes (mtDNA) of three P. pulmonarius strains - two monokaryotic commercial (J1-13 and ZA3) and one wild (X1-15) - were sequenced and analyzed. In ZA3 and X1-15, the mtDNA molecule was found to be a single circle of 68,305 bp and 73,435 bp, respectively. Both strains contain 14 core protein-coding genes and two ribosomal RNA (rRNA) subunit genes. The ZA3 strain has 22 transfer RNA (tRNA) genes and nine introns: eight in cytochrome c oxidase subunit 1 (coxl), and one in the rRNA large subunit (rnl). Monokaryotic J1-13 and ZA3 mtDNAs were found to be similar in their structure. However, the wild strain X1-15 contains 25 tRNA genes and only seven introns in coxl. Open reading frames (ORFs) of ZA3/J1-13 and X1-15 encode LAGLIDADG, ribosomal protein S3, and DNA polymerase II. In addition, mtDNA inheritance in J1-13, ZA3, and X1-15 was also studied. Results showed that the mtDNA inheritance pattern was uniparental and closely related to dikaryotic hyphal location with respect to the parent. Results also show that mtDNA inheritance is influenced by both the parental nuclear genome and mitogenome in the zone of contact between two compatible parents. In summary, this analysis provides valuable information and a basis for further studies to improve our understanding of the inheritance of fungal mtDNA.

Melasma is a common but complex skin condition concerning cosmetic problems. Tranexamic acid (TA) has been proved to be effective in treatment of melasma with still unclear mechanisms. Here, we show that VEGF165 enhanced the expression of VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2 and NRP-1) in human umbilical vein endothelial cells (HUVECs), which was attenuated by TA. VEGF165 also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in HUVECs, which was again abolished by TA. TA further showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting cell proliferation, migration, invasion and tube formation of HUVECs induced by VEGF165, suggesting that TA could inhibit angiogenesis by targeting VEGFRs in HUVECs. In addition, VEGF165 enhanced the expression of VEGFRs and promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in normal human melanocytes, which were also attenuated by TA. Furthermore, TA showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting tyrosinase activity, melanin production and even melanogenic proteins induced by VEGF165, suggesting that TA could reduce melanogenesis via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that TA can inhibit angiogenesis and melanogenesis in vitro at least in part by targeting VEGFRs, which may offer a new understanding of the pathogenesis of melasma as well as the molecular mechanism for TA in treatment of the disease.

To investigate the effects of different orthodontic treatments on gingival crevicular fluid chemokine CX3CL1, nuclear factor κB receptor activating factor ligand/osteoprotegerin(RANKL/OPG) levels in patients with malocclusion.Ninety-six patients with malocclusion who were scheduled to undergo orthodontic treatment were randomly divided into four groups. All patients were treated with square wire appliance, and 0, 50, 150, 250 g of far-distal orthodontic force were given respectively. The levels of CX3CL1 and RANKL/OPG in gingival crevicular fluid were detected in four groups after 1, 2, 3, and 4 weeks of treatment. SPSS 25.0 software package was used for statistical analysis of the date.The levels of CX3CL1, RANKL and RANKL/OPG in the gingival crevicular fluid of the four groups were continuously increased after treatment for 1-3 weeks, and decreased after 4 weeks of treatment (P0.05). The OPG in the gingival crevicular fluid was at a low level after 1-3 weeks of treatment. There was an increase after 4 weeks of treatment (P0.05). The levels of CX3CL1, RANKL, OPG and RANKL/OPG in gingival crevicular fluid increased gradually in group A, B, C and D (P0.05), and the differences between the groups were statistically significant (P0.05).The levels of CX3CL1 and RANKL/OPG in gingival crevicular fluid are closely related to orthodontic force and treatment time, and can be used as an index to evaluate orthodontic treatment of alveolar bone remodeling.

Invasive species of Pomacea snails are of growing concern when it comes to the conservation of global biodiversity. Pomacea canaliculata has been listed among the world’s 100 worst invasive species. In this work, phylogeographic patterns and the demographic history of P. canaliculata and P. maculata from different countries were analyzed using mtDNA cytochrome c oxidase subunit-I (COI) sequences. The results showed that P. canaliculata and P. maculata had high genetic diversity, significant genetic differentiation, limited gene flow and stable population dynamics among different countries. Genetic diversity of P. canaliculata was higher than P. maculata. Our study will also provide important information for the effective prevention and control of the spread of Pomacea snails.

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.

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 COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients. Methods Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients. Results Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). For severe patients, the counts of T cell, CD4+ T cell, CD8+ T cell gradually decreased with the increased delayed hospitalization (p = 0.001, 0.03, and + T cell gradually decreased with the increased delayed hospitalization (both p p = 0.007, and 0.002, respectively). For mild patients, only the NK cell count was gradually decreased with the increased delayed hospitalization (p = 0.012). Conclusion T lymphocyte and its subset negatively correlated with disease severity, CT manifestation and delayed hospitalization. The counts of lymphocyte subset were changed more profound than their proportions.

High density microprocessor packages are being deployed to achieve system performance improvements. However, the non-uniform heat dissipation characteristics of such packages has led to renewed interest in vapor chambers and heat pipes for heat spreading and transport. In this paper an approach to model the thermo-hydrodynamic performance of vapor chambers for cooling of microprocessor packages is presented. Model validation against data available in literature showed a very good agreement. The validated model was then used to study the performance sensitivity to vapor chamber design and operational parameters such as wick thickness, wick type, evaporator side heat input and condenser side heat extraction.

Melasma is a common but complex skin condition concerning cosmetic problems. Tranexamic acid (TA) has been proved to be effective in treatment of melasma with still unclear mechanisms. Here, we show that VEGF165 enhanced the expression of VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2 and NRP-1) in human umbilical vein endothelial cells (HUVECs), which was attenuated by TA. VEGF165 also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in HUVECs, which was again abolished by TA. TA further showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting cell proliferation, migration, invasion and tube formation of HUVECs induced by VEGF165, suggesting that TA could inhibit angiogenesis by targeting VEGFRs in HUVECs. In addition, VEGF165 enhanced the expression of VEGFRs and promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in normal human melanocytes, which were also attenuated by TA. Furthermore, TA showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting tyrosinase activity, melanin production and even melanogenic proteins induced by VEGF165, suggesting that TA could reduce melanogenesis via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that TA can inhibit angiogenesis and melanogenesis in vitro at least in part by targeting VEGFRs, which may offer a new understanding of the pathogenesis of melasma as well as the molecular mechanism for TA in treatment of the disease.

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.