Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

Unveiling the identity of Diaurora Cockerell, 1903 (Bivalvia, Unionidae): morphology, molecular phylogenetics, and the description of a new species.

The monotypic freshwater mussel genus Diaurora Cockerell, 1903 has long been enigmatic due to its rarity and morphological confusion with Acuticosta. In this study, we comprehensively redescribed Diauroraaurorea (Heude, 1883) through a detailed analysis of shell morphology and molecular phylogenetics of recently collected specimens. Moreover, a new species, Diauroralaevesp. nov., was identified from the Fuyishui River, a tributary of the Zishui River in Shaoyang County, Shaoyang City, Hunan Province, China. Molecular phylogenetic analyses showed that D.aurorea and D.laevesp. nov. were reciprocally monophyletic and formed a clade as sister to Schistodesmus. Our study underscores the necessity of further exploring the diversity of freshwater mussels in understudied small tributaries throughout China.

AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Comparison of Rhomboid Intercostal Block, Erector Spinae Plane Block, and Serratus Plane Block on Analgesia for Video-Assisted Thoracic Surgery: A Prospective, Randomized, Controlled Trial.

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-1ß 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-1ß, 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.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Complete mitochondrial genome of the freshwater snail Tarebia granifera (Lamarck, 1816) (Gastropoda: Cerithioidea: Thiaridae).

The freshwater gastropod Tarebia granifera (Lamarck, 1816) is found in Taiwan, Hainan, and Guangdong provinces in China, and is one of the main intermediate hosts of trematodes that infect humans. The taxonomic positions of some cerithioidean families are still unclear, and whole mitochondrial genome studies are scarce in the Thiaridae. In this study, we describe the complete mitogenome of Tarebia granifera (Lamarck, 1816). The mitogenome is 15,555 bp in length, with a total of 37 genes, including 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. It is consistent with the essential features of previously studied mitochondrial genomes of species belonging to the superfamily Cerithioidea. Our study demonstrates the usefulness of mitogenomic data for resolving phylogenetic relationships of families within Cerithioidea and may also contribute to the prevention and control of the parasitic diseases caused by trematodes, which use T. granifera as an intermediate host.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

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.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining.

Gastric cancer (GC) is still a vital malignant cancer across the world with unsatisfactory prognostic results. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. The present research intends to explore the expression level of MATN3 in patients with GC and to explore the prognosis significance of MATN3. In this study, we observed that the MATN3 expression was remarkably upregulated in GC samples in contrast to noncancer samples. Clinical analyses unveiled that high MATN3 expression was related to age, tumor status, and clinical stages. Survival analyses unveiled that patients with high MATN3 expression displayed a poorer overall survival and progression-free survival than those with low MATN3 expression. The AUC of the relevant ROC curve for 1 year, 3 years, and 5 years of survival is 0.571, 0.596, and 0.720, separately. Multivariate assays revealed that MATN3 expression and stage were independent predictors of poor prognosis of GC patients. A meta-analysis unveiled that high MATN3 expression was tightly associated with better overall survival. Overall, our data indicated that MATN3 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

Complete maternal mitochondrial genome of the freshwater mussel Cuneopsis celtiformis (Bivalvia: Unionidae).

The genus Cuneopsis Simpson, 1900 comprises seven valid species, and Cuneopsis celtiformis (Heude, 1874) is the type species of this genus. Previous phylogenetic studies using complete mitochondrial genomes showed that Cuneopsis was not monophyletic, but the result was hampered by incomplete species sampling and lack of the type species of this genus. In this study, we collected C. celtiformis from the type locality and determined its complete maternal mitochondrial genome. This mitogenome is 15,922 bp in length and contains 14 protein-coding genes (including one F-orf), two rRNA genes, 22 tRNA genes, and 1 putative control region. Our mitochondrial phylogenomic analysis confirms that currently recognized genus Cuneopsis is polyphyletic, and C. celtiformis is the closest to C. heudei with high maximum likelihood bootstrap support value. Comprehensive sampling of all Cuneopsis species is needed for phylogenetic analysis to erect new genera in future studies.

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

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.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

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.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Complete mitochondrial genome of the land snail Euphaedusa planostriata (Gastropoda: Stylommatophora: Clausiliidae).

Clausiliidae snails have been of great interest to conchologists for their unique clausilium structure and rich species diversity. We described the complete mitochondrial genome of Euphaedusa planostriata (Heude, 1882). The mitogenome is 15,041bp in length, with a total of 37 genes, including 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. It is consistent with the basic characteristics of the known stylommatophoran mitochondrial genome. Phylogenetic analysis using mitogenomes showed that Euphaedusa planostriata is clustered with Albinaria caerulea, supporting the monophyly of this family. Our study provides valuable information that can be used toward the conservation genetics, taxonomy and evolution of clausiliid snails.

[Effects of different orthodontic treatments on sputum chemokines CX3CL1, RANKL/OPG levels in patients with malocclusion].

PURPOSE: 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. METHODS: 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. RESULTS: 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 (P<0.05). 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 (P<0.05). The levels of CX3CL1, RANKL, OPG and RANKL/OPG in gingival crevicular fluid increased gradually in group A, B, C and D (P<0.05), and the differences between the groups were statistically significant (P<0.05). CONCLUSIONS: 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.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

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.

Hepatoprotective effects of loach (Misgurnus anguillicaudatus) lyophilized powder on dimethylnitrosamine-induced liver fibrosis in rats.

This study investigates the hepatoprotective effects and the potential therapeutic mechanisms of loach (Misgurnus anguillicaudatus) lyophilized powder (MLP) on dimethylnitrosamine (DMN) induced liver fibrosis in rats. After treatment with MLP (50, 100, 200 mg/kg), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) and hydroxyproline (Hyp) levels were detected, to assess the destruction of hepatocytes and the extent of liver fibrosis. Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), Laminin (LN), procollagen type-III (PC-III), collagen type-IV (C-IV), and transforming growth factor-ß1 (TGF-ß1) contents in serum were all tested using ELISA kits. Alpha-smooth muscle actin (α-SMA) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) protein contents and distribution were evaluated using western blot and immunohistochemical analysis. MLP significantly decreased the serum concentrations of ALT, AST, Hyp, HA, LN, PC-III, C-IV, MMP-2, TIMP-1, α-SMA and TGF-ß1, while increasing the contents of Alb and MMP-9. No significant changes on TP serum concentrations were observed. These results suggest that MLP has anti-hepatic fibrosis effects and its mechanism may be associated with the attenuation of extracellular matrix (ECM) synthesis, the acceleration of ECM degradation, inhibition of hepatic stellate cells (HSCs) activation and TGF-ß1 expression.

Tranexamic Acid Inhibits Angiogenesis and Melanogenesis in Vitro by Targeting VEGF Receptors.

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.

Mitochondrial genome and diverse inheritance patterns in Pleurotus pulmonarius.

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.

Biotypes of major depressive disorder: Neuroimaging evidence from resting-state default mode network patterns.

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.