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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Many patients with osteosarcoma readily develop resistance to chemotherapy and have an extremely dismal prognosis. Dioscin, a saponin, is known to exhibit potent anticancer activities and induce cellular death of a variety of cancer types. However, the inhibitory effect of dioscin on osteosarcoma cells and its underlying mechanisms have not been fully elucidated. We investigated the responses of human U2-OS and MG63 osteosarcoma cells to dioscin with regard to proliferation, apoptosis, migration, and invasion, and studied the effect of dioscin on MAPK-related proteins by western blot analysis assays. Dioscin inhibited osteosarcoma cell proliferation, migration, and invasion. Moreover, it induced osteosarcoma cell apoptosis via reactive oxygen species (ROS)-dependent apoptotic signaling. N-acetylcysteine, a reactive oxygen species inhibitor, suppressed dioscin-induced apoptosis, indicating that ROS play an essential role in dioscin-induced apoptosis. Western blot analysis assays showed that p38 MAPK was upregulated after dioscin treatment, and that dioscin induced apoptosis by upregulating ROS-mediated p38 MAPK signaling. Our study suggests that dioscin possesses antitumor activities against human osteosarcoma cells, inhibits osteosarcoma cell proliferation, migration and invasion, and induces osteosarcoma cell apoptosis through upregulating ROS-mediated p38 MAPK signaling. This study may provide a new therapeutic strategy and potential clinical applications for the treatment of osteosarcoma.

Major depressive disorder (MDD) as a dysfunction of neural circuits and brain networks has been established in modern neuroimaging sciences. However, the brain state transitions between MDD and health through external stimulation remain unclear, which limits translation to clinical contexts and demonstrable clinical utility. We propose a framework of the large-scale whole-brain network model for MDD linking the underlying anatomical connectivity with functional dynamics obtained from diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Then, we further explored the optimal brain regions to promote the transition of brain states between MDD and health through external stimulation of the model. Based on the whole-brain model successfully fitting the brain state space in MDD and the health, we demonstrated that the transition from MDD to health is achieved by the excitatory activation of the limbic system and from health to MDD by the inhibitory stimulation of the reward circuit. Our finding provides novel biophysical evidence for the neural mechanism of MDD and its recovery and allows the discovery of new stimulation targets for MDD recovery.

Sorghum, the fifth largest cereal crop, has high value as a staple food and raw material for liquor and vinegar brewing. Due to its high biomass and quality, it is also used as the second most planted silage resource. No fragrant sorghums are currently on the market. Through CRISPR/Cas9-mediated knockout of SbBADH2, we obtained sorghum lines with extraordinary aromatic smell in both seeds and leaves. Animal feeding experiments showed that fragrant sorghum leaves were attractable. We believe this advantage will produce great value in the sorghum market for both grain and whole biomass forage.

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.

To explore the biological activity of transmembrane prostateandrogen induced RNA (PMEPA1) in human pancreatic cancer (hPAC) cells and its drug sensitivity to gemcitabine (GEM) and cisplatin (DDP). Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) were consulted to indicate the expression of PMEPA1 in hPAC tissues and cells. Quantitative real-time PCR (RT-qPCR) and western blot were performed to verify the indication. RT-qPCR and western blot also detected the expressions of PTEN/PI3K/AKT before and after transfection of PMEPA1 siRNA plasmids. Cell counting Kit-8 (CCK-8) and EdU staining were performed to examine cell proliferation before and after transfection of phosphatase and tensin homologue delet2ed on chromosome ten (PTEN) siRNA plasmids. Transwell and wound healing detected the invasion and migration of hPAC cells. The expressions of MMP-2 and MMP-9 were detected by western blot. After GEM or DDP treatment, cell viability was observed by commercial kits and cell apoptosis by flow cytometry. GEPIA and CCLE predicted increased expression of PMEPA1 in hPAC tissues and cells, which was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot. PMEPA1 was also shown to be associated with disease-free survival. Transfection of PMEPA1 siRNA plasmids affected the expressions of PTEN/PI3K/AKT. PMEPA1 interference inhibited the proliferation, invasion and migration of hPAC cells. Furthermore, PMEPA1 interference also enhanced the sensitivity of hPAC cells to GEM and DDP via PTEN interference. PMEPA1 interference inhibits the proliferation, invasion and migration of pancreatic cancer cells and enhances the sensitivity to GEM and cisplatin by activating PTEN/PI3K/AKT signaling.

Multi-dimensional data exploration is a classic research topic in visualization. Most existing approaches are designed for identifying record patterns in dimensional space or subspace. In this paper, we propose a visual analytics approach to exploring subset patterns. The core of the approach is a subset embedding network (SEN) that represents a group of subsets as uniformly-formatted embeddings. We implement the SEN as multiple subnets with separate loss functions. The design enables to handle arbitrary subsets and capture the similarity of subsets on single features, thus achieving accurate pattern exploration, which in most cases is searching for subsets having similar values on few features. Moreover, each subnet is a fully-connected neural network with one hidden layer. The simple structure brings high training efficiency. We integrate the SEN into a visualization system that achieves a 3-step workflow. Specifically, analysts (1) partition the given dataset into subsets, (2) select portions in a projected latent space created using the SEN, and (3) determine the existence of patterns within selected subsets. Generally, the system combines visualizations, interactions, automatic methods, and quantitative measures to balance the exploration flexibility and operation efficiency, and improve the interpretability and faithfulness of the identified patterns. Case studies and quantitative experiments on multiple open datasets demonstrate the general applicability and effectiveness of our approach.

This study aimed to explore the effect of performing remote health education via WeChat to improve the pre-operative nutritional status of non-restrictive ventricular septal defects (VSD).A prospective randomised controlled study was conducted in a provincial maternity and child hospital in China. Participants were randomised regarding education to the intervention group (WeChat) and the control group (leaflets). The nutritional status and complications of the patients were compared after intervening for 1 month.Nutrient status comparison at 1 month after intervention showed that the body weight, head circumference, haemoglobin, albumin and pre-albumin of the WeChat group were significantly higher than those of the leaflet group (P 0.05). The STRONGkids score of the WeChat group was significantly lower than that of the leaflet group (P 0.05). The incidence of feeding intolerance and respiratory tract infection in the WeChat group was significantly lower than that found in the leaflet group (P 0.05). There was no significant difference in the incidence of liver insufficiency and jaundice between the two groups (P 0.05).Providing pre-operative feeding and care guidance for parents of infants with non-restrictive VSD, via remote health education through WeChat, can effectively improve nutritional status and reduce the risk of malnutrition and feeding complications.

Borna disease virus 1 (BoDV-1) is a nonsegmented, negative-strand RNA virus that infects mammals including humans. BoDV-1 strains occur globally, dominate the species Mammalian 1 bornavirus, and display highly conserved genomes and persistent infection (brain, blood). Subclinical infections prevail but the rare fatal outcomes even in people need awareness and risk assessment. Although BoDV-1 strains were successfully isolated, only limited full genomic sequences are available. In this study, the entire genomes of two natural BoDV-1 isolates (Hu-H2, Equ-Cres) and one vaccine strain (DessVac) were sequenced. They were compared with 20 genomes and 20 single-gene sequences (N and P) of worldwide human strains from psychiatric and neurologic patients and animal strains from horses with Borna disease available at GenBank. Phylogenetic analyses confirmed a low divergence not exceeding 5.55%, 5.34%, and 4.94% at the genome, P-gene, and N-gene level, respectively, characteristic of BoDV-1. Human viruses tended to cluster at the country level but appeared to be independent of hosts' diseases and/or time of isolation. Notably, our data also indicated that human viruses provided individual genetic signatures but exhibited no distinct genotypes that separated them from animal strains. Sequence similarities thus occurred between different host species and distant geographic regions, supporting global BoDV-1 prevalence. Overall low genetic divergence among BoDV-1 viruses shown here also argued against zoonotic concepts, requiring further clarification beyond sequence similarities. Finally, unlike shared sequence conservation, phenotyping of natural and laboratory variants revealed that they manipulated host cells differently, underpinning the authenticity of the human BoDV-1 strains.

Glioblastoma (GBM) is the most universal type of primary brain malignant tumour, and the prognosis of patients with GBM is poor. S100A11 plays an essential role in tumour. However, the role and molecular mechanism of S100A11 in GBM are not clear. Here, we found that S100A11 was up‐regulated in GBM tissues and higher S100A11 expression indicated poor prognosis of GBM patients. Overexpression of S100A11 promoted GBM cell growth, epithelial‐mesenchymal transition (EMT), migration, invasion and generation of glioma stem cells (GSCs), whereas its knockdown inhibited these activities. More importantly, S100A11 interacted with ANXA2 and regulated NF‐κB signalling pathway through decreasing ubiquitination and degradation of ANXA2. Additionally, NF‐κB regulated S100A11 at transcriptional level as a positive feedback. We also demonstrated the S100A11 on tumour growth in GBM using an orthotopic tumour xenografting. These data demonstrate that S100A11/ANXA2/NF‐κB positive feedback loop in GBM cells that promote the progression of GBM.

As a widely distributed species along the Irtysh River, Phoxinus phoxinus ujmonensis (Kaschtschenko, 1899) was used as a model to investigate genetic diversity and population structure as well as the influence of environmental factors on population genetics. In this study, we specifically developed 12 polymorphic microsatellite loci. The analysis of microsatellite and mtDNA markers revealed a high and a moderate genetic diversity across seven populations, respectively. Moderate differentiation was also detected among several populations, indicating the impact of habitat fragmentation and divergence. The absence of isolation by distance implied an extensive gene flow, while the presence of isolation by adaptation implied that these populations might be in the process of adapting to divergent habitats. Correlation analysis showed that abiotic factors like dissolved oxygen, pH, total dissolved solids, and conductivity in water as well as biotic factors like plankton diversity and fish species diversity had impact on genetic diversity and divergence in P. phoxinus ujmonensis populations. The results of this study will provide an insight into the effect of environmental factors on genetic diversity and contribute to the study of population genetics of sympatric species.

Recent study has reported that microRNA-628-5p (miR-628-5p) is involved in the development of epithelial ovarian cancer; however, the mechanisms of miR-628-5p in glioma remain unclear. In this study, we explored the potential biological roles of miR-628-5p in glioma. First, we found that miR-628-5p was decreased in the tissues and cells (U87 and T98) of glioma. Second, overexpressing miR-628-5p reduced the ability of glioma cells' proliferation and induced glioma cells' cycle arrest in G1. Then, we found that miR-628-5p directly bound to the 3'-untranslated region of DDX59 and decreased the protein level of DDX59. The decrease of DDX59 was found to lead to the decrease of p-AKT. Mechanistic studies revealed that restoring the expression of DDX59 alleviated miR-628-5p-induced inhibition of proliferation of glioma. These findings suggest that the miR-628-5p/DDX59 axis has a key role in the development of glioma, and miR-628-5p might be a new therapeutic target against glioma.

The pseudogene annexin A2 pseudogene 2 (ANXA2P2) is highly expressed in glioblastoma (GBM). However, its role and mechanism involved in the progression of GBM remain poorly understood. ANXA2P2 messenger RNA expression was measured by quantitative reverse transcription-polymerase chain reaction. The protein levels were detected by Western blot. Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase (LDH) release assays. Cell invasive ability was investigated by the transwell assay and by epithelial-mesenchymal transition (EMT). Cell apoptosis was examined by flow cytometry. The results showed that ANXA2P2 expression was increased in GBM tissues and cells. Silencing of ANXA2P2 inhibited the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway in GBM cells. Knockdown of ANXA2P2 decreased cell viability, promoted LDH release, suppressed cell invasive ability, and EMT, and induced cell apoptosis in GBM cells. The addition of the PI3K/PKB activator 740Y-P abrogated the effects of ANXA2P2 knockdown on cell viability, LDH release, invasive ability, and apoptosis. In conclusion, knockdown of ANXA2P2 inhibited cell viability and invasion but promoted the apoptotic rate by suppressing the PI3K/PKB pathway in GBM cells. ANXA2P2 may represent a new target for the treatment of GBM.

Aging is a critical factor affecting physical health and disease in mammals. Emerging evidence indicates that aging may affect the gut bacteriome in cynomolgus macaques, but little is known about whether or how the gut virome changes with age. Here, we compared the DNA gut viral composition of 16 female cynomolgus monkeys (Macaca fascicularis) at three life stages (young, adult, and old) using the shotgun metagenome sequencing method. We found that the DNA gut virome from these monkeys differed substantially among the three groups. The gut viruses were dominated by bacteriophages, the most abundant of which was the Caudovirales order (i.e., Siphoviridae, Myoviridae, and Podoviridae families). Additionally, the co‐occurrence analysis revealed that the age‐related bacteriophages were correlated in an extensive and complex manner with the main intestinal bacteria (i.e., Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla). Furthermore, the age‐related DNA gut viral functions were enriched for genetic information processing, nucleotide, and folate metabolism. Our gut virome analysis provides new insight into how aging influences the gut virome of non‐human primates., We characterized changes of the DNA gut virome associated with age in female crab‐eating macaques. The structural and functional profiles of the gut DNA virome differed significantly among the three age groups. The gut virome was dominated by dsDNA phages, especially the Caudovirales order, which showed strong correlations with the highly prevalent gut bacteria. Our findings suggest that modulating the intestinal virome may be beneficial for the treatment of aging.

Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α‐phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ‐free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.

The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic-pituitary-adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Aiming to further investigate the mechanisms of MDD, liquid chromatography-tandem mass spectrometry was employed to measure target metabolites in the hippocampus (HIPPO) of chronic social defeat stress model mice. Compared with control mice, stress-susceptible mice showed a reduction of 5-hydroxyindoleacetic acid and kynurenic acid in the tryptophan pathway, and an increased level of dopamine in the catecholamine pathway, while stress-resilient mice displayed a reduction of 5-hydroxytryptamine in the tryptophan pathway. The altered levels of key molecules related to the tryptophan or dopamine metabolic pathways were validated by real-time quantitative polymerase chain reaction or western blotting. Comparative analysis with previous targeted metabolomics results in the prefrontal cortex (PFC) of chronic social defeat stress mice revealed that the altered metabolites manifested in specific brain areas, and only the dopamine metabolic pathway was perturbed in both the HIPPO and PFC after stress. Additionally, correlation analysis validated that levels of kynurenic acid in the HIPPO, along with glutamic acid, L-3, 4-dihydroxyphenylalanine, and vanillylmandelic acid in the PFC, were correlated with depression-like behaviors. This study provides a unique perspective on the potential molecular mechanisms of stress susceptibility and stress resilience.

Discriminating depressive episodes of bipolar disorder (BD) from major depressive disorder (MDD) is a major clinical challenge. Recently, gut microbiome alterations are implicated in these two mood disorders; however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, using 16S ribosomal RNA (rRNA) gene sequencing, the microbial compositions of 165 subjects with MDD are compared with 217 BD, and 217 healthy controls (HCs). It is found that the microbial compositions are different between the three groups. Compared to HCs, MDD is characterized by altered covarying operational taxonomic units (OTUs) assigned to the Bacteroidaceae family, and BD shows disturbed covarying OTUs belonging to Lachnospiraceae, Prevotellaceae, and Ruminococcaceae families. Furthermore, a signature of 26 OTUs is identified that can distinguish patients with MDD from those with BD or HCs, with area under the curve (AUC) values ranging from 0.961 to 0.986 in discovery sets, and 0.702 to 0.741 in validation sets. Moreover, 4 of 26 microbial markers correlate with disease severity in MDD or BD. Together, distinct gut microbial compositions are identified in MDD compared to BD and HCs, and a novel marker panel is provided for distinguishing MDD from BD based on gut microbiome signatures., Gut microbiome alterations are implicated in major depressive disorder (MDD) and bipolar disorder (BD); however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, the distinct microbial covarying units for MDD and BD are first identified, and microbial markers for distinguishing MDD from BD based on gut microbiome signatures are provided.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis.