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Objective To investigate the value of serum 5-hydroxytryptamine （5-HT） and interleukin-6 （IL-6） levels in predicting depression in patients with Alzheimer’s disease （AD）. Methods Ninety-six AD patients without depression were prospectively recruited and followed-up for 2 years. During follow-up， all patients were divided into the AD complicated with depression group （depression group） and AD without depression group （non-depression group） according to whether they were complicated by depression. Baseline data and serum 5-HT， IL-6， brain-derived neurotrophic factor （BDNF） and glucocorticoid （GC） levels at baseline were compared between two groups. The correlation between serum 5-HT and IL-6 levels and HAMD score was assessed by Pearson correlation analysis. The effect of serum 5-HT and IL-6 levels on depression in AD patients was evaluated by logistic regression analysis， and the receiver operating characteristic （ROC） curve was drawn. Results A total of 87 patients were included after 9 patients were excluded. The baseline data were comparable between two groups （all P > 0.05）. In the depression group（n = 37）， serum 5-HT level was significantly lower， whereas serum IL-6 level was significantly higher compared with those in the non-depression group （n = 50）（both P < 0.01）. Serum 5-HT level was negatively correlated with HAMD score （r = -0.572， P < 0.01）， whereas serum IL-6 level was positively correlated with HAMD score （r = 0.609， P < 0.01）. Serum 5-HT level was a protective factor， whereas serum IL-6 level was a risk factor for depression in AD patients （both P < 0.05）. The area under the ROC curve （AUC） for serum 5-HT level was 0.747， the sensitivity was 64.00%， and the specificity was 86.49%， respectively. The AUC of serum IL-6 level was 0.732， the sensitivity was 78.42%， and the specificity was 67.57%， respectively. The AUC constructed by combining serum 5-HT and IL-6 levels was 0.790， the sensitivity was 76.75%， and the specificity was 87.71%， respectively. Conclusions Abnormal serum 5-HT and IL-6 levels are correlated with depression in AD patients. These two combined can be used to predict the occurrence of depression in AD patients.

Cervical cancer (CC) is the most common malignant tumor in women, and its prognosis is poor. The key genes and pathways of CC need to be further discovered. GEO2R was used to identify differentially expressed genes (DEG), GO and KEGG enrichment were analyzed by DAVID. Then, the PPI network is constructed with STRINGS. The HUB gene and module of DEGS were obtained by Cytoscape. Finally, GEPIA also analyzed the differential expression and survival of key genes. 234 DEG were extracted from GSE9750. The uterus is the fourth organ highlighted in the concentrated analysis. The functional changes of DEGS are mainly related to cell cycle progression, cell cycle, helicase activity, DNA helicase activity, exosome and p53 signal pathway. In addition, five HUB genes and one key module were identified. Survival analysis showed that MCM2 and GINS2 were significantly correlated with overall survival. Expression analysis showed that MCM2 and GINS2 were highly expressed in cancer tissues, but low in normal tissues, which was consistent with the results of GEO analysis. Correlation analysis showed that there was a significant positive correlation between MCM2 and GINS2. This study suggests that MCM2 and GINS2 may be new biomarkers to predict the prognosis of CC. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, but there is currently no effective treatment method. Probiotics have been used as an adjunct therapy for NAFLD, but the mechanism is not clear. This study used Bifidobacterium longum BL19 (BL‐19) to treat the NAFLD mice induced by a high‐fat diet, and explored the treatment mechanism through gut microbiota and serum metabolomics techniques. We found that BL‐19 effectively prevented rapid weight gain in NAFLD mice and reduced their overall food and energy intake, decreased liver inflammatory factors expressions, and increased the bile acid synthetase enzyme CYP7A1 and superoxide dismutase. After BL‐19 treatment, the abundances of butyric acid bacteria (Oscillospira and Coprococcus) in the feces of mice increased significantly, and the concentration of butyric acid also increased significantly. We believe that BL‐19 promotes the production of butyrate in the intestines, which in turn regulates the activity of CYP7A1 in the liver and bile acid synthesis, ultimately treating liver inflammation and lipid accumulation in NAFLD mice. Serum metabolomics results indicated that BL‐19 affected multiple pathways related to inflammation and lipid metabolism in NAFLD mice. These findings suggest that BL‐19 shows promise as an adjunct therapy for NAFLD, as it can significantly improve oxidative stress, reduce inflammation in the liver, and decrease lipid accumulation. [ABSTRACT FROM AUTHOR]

Magnetic MnFe2O4 nanoparticles were successfully prepared by the rapid combustion method at 500 °C for 2 h with 30 mL absolute ethanol, and were characterized by SEM, TEM, XRD, VSM, and XPS techniques, their average particle size and the saturation magnetization were about 25.3 nm and 79.53 A·m2/kg, respectively. The magnetic MnFe2O4 nanoparticles were employed in a fixed bed experimental system to investigate the adsorption capacity of Hg0 from air. The MnFe2O4 nanoparticles exhibited the large adsorption performance on Hg0 with the adsorption capacity of 16.27 μg/g at the adsorption temperature of 50 °C with the space velocity of 4.8×104 h-1. The VSM and EDS results illustrated that the prepared MnFe2O4 nanoparticles were stable before and after adsorption and successfully adsorbed Hg0. The TG curves demonstrated that the mercury compound formed after adsorption was HgO, and both physical and chemical adsorption processes were observed. Magnetic MnFe2O4 nanoparticles revealed excellent adsorbance of Hg0 in air, which suggested that MnFe2O4 nanoparticles be promising for the removal of Hg0. [ABSTRACT FROM AUTHOR]

Magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods were successfully prepared via calcination reduction process using glucose as reductant, and they were characterized by SEM, TEM, XRD and VSM techniques. The influences of additive concentration, solution volume, reaction temperature and reaction time on morphology and the properties of Fe3O4/α-Fe2O3 heterogeneous nanorods were investigated. Firstly, α-Fe2O3 nanorods were prepared by the hydrothermal approach, and the FeCl3 concentration of 20 mM, the NH4H2PO4 concentration of 0.96 mM, the hydrothermal volume of 60 mL, the hydrothermal temperature of 180 °C, and hydrothermal time of 12 h were selected as the optimum conditions. Secondly, magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods calcined at 600 °C for 3 h with the mass ratio of 1:20 for α-Fe2O3 nanorods and glucose were constructed with largest saturation magnetization of 78.2 emu/g, their average length and average diameter were about 215.0 nm and 79.2 nm, respectively. An optimization process for the fabrication of magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods was introduced in this paper. Thereinto, α-Fe2O3 nanorods as a precursor were fabricated by hydrothermal method, and using glucose as a reduction agent to prepare the results products by high-temperature calcination. The influences of FeCl3 concentrations, NH4H2PO4 concentration, solution volume, hydrothermal temperature, hydrothermal time and the ratio of the precursors and glucose on the morphologies and magnetic properties of α-Fe2O3 and magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods were investigated, and their influence rules were revealed. [ABSTRACT FROM AUTHOR]

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole‐organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self‐fertilized and cultured in the same chamber. Despite the tremendous progress made in single‐cell proteomic analysis, there is few single‐worm proteomics studies about aging. Here, we apply single‐worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast‐aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter‐individual proteomic variation during aging and revealed contributing factors that distinguish fast‐aging individuals from their siblings. [ABSTRACT FROM AUTHOR]

Cryptotanshinone (CT), a lipophilic compound extracted from roots of Salvia miltiorrhiza Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear. This study examines the effect of CT on ischaemic stroke. We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, n = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group. The 50% inhibitory concentration (IC50) of CT on CD4+ cell damage was 485.1 μg/mL, and median effective concentration (EC50) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4+CD25+ Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4+ T cells of the MCAO model. Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignant tumors in the world. As far as we know, no biomarker has been widely accepted for early diagnosis and prognosis prediction of GC. The purpose of this study is to find potential biomarkers to predict the prognosis of GC. The differentially expressed gene (DEG) was analyzed from GSE93774. Enrichr was used to analyze the gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the enrichment of transcription factors (TF), miRNA, and kinase. GO analysis showed DEGs was enriched in the process of amino acid metabolism. Pathway results showed DEGs was mainly enriched in cell cycle. Propionyl CoA carboxylase alpha (PCCA), Enoyl coenzyme A hydratase short chain 1 (ECHS1), and 3-hydroxyacyl-CoA dehydrogenase (HADH) have prognostic value in patients with GC. ECHS1 and HADH genes were significantly associated with disease-free survival. There was a significant correlation between PCCA and overall survival rate. The results of this study suggest that PCCA, ECHS1, and HADH may be new biomarkers for predicting the prognosis of GC. [ABSTRACT FROM AUTHOR]

Zinc (Zn) deficiency is a widespread agricultural problem in arable soils of the whole world. However, the molecular mechanisms underlying Zn‐deficiency response are largely unknown. Here, we analyzed the transcriptomic profilings of soybean leaves and roots in response to Zn deficiency through Illumina's high‐throughput RNA sequencing in order to understand the molecular basis of Zn‐deficiency response in the plants. A total of 614 and 1011 gene loci were found to be differentially expressed in leaves and roots, respectively, and 88 loci were commonly found in both leaves and roots. Twelve differentially expressed genes (DEGs) were randomly selected for validation by quantitative reverse transcription polymerase chain reaction, and their fold changes were similar to those of RNA‐seq. Gene ontology enrichment analysis showed that ion transport, nicotianamine (NA) biosynthetic process and queuosine biosynthetic process were enriched in the upregulated genes, while oxidation–reduction process and defense response were enriched in the downregulated genes. Among the DEGs, 20 DEGs are potentially involved in Zn homeostasis, including seven ZRT, IRT‐related protein (ZIP) transporter genes, three NA synthase genes, and seven metallothionein genes; 40 DEGs are possibly involved in diverse hormonal signals such as auxin, cytokinin, ethylene and gibberellin; nine DEGs are putatively involved in calcium signaling; 85 DEGs are putative transcription factor genes. Nine DEGs were found to contain zinc‐deficiency‐response element in their promoter regions. These results could provide comprehensive insights into the soybean response to Zn deficiency and will be helpful for further elucidation of the molecular mechanisms of Zn‐deficiency response and Zn‐deficiency tolerance in plants. [ABSTRACT FROM AUTHOR]

Microcystin-leucine-arginine (MC-LR) is a cyclic heptapeptide compound produced by cyanobacteria with strong cytotoxicity. Previous studies have confirmed that MC-LR could exert toxic effects on the genitourinary system, but there are few reports about its toxicity to the bladder. In this study, we investigated the effects of MC-LR on mouse bladder and human bladder epithelial cells (SV-HUC-1 cells). We observed that the bladder weight and the number of bladder epithelial cells were markedly increased in mice following chronic low-dose exposure to MC-LR. Further investigation showed that MC-LR activates AKT/NF-kB signaling pathway to induce the production of proinflammatory cytokines TNF-α and IL-6. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in bladder tissue was increased and the relative migration and invasion capacities of SV-HUC-1 cells were enhanced upon exposure to MC-LR. In conclusion, these results suggest that chronic exposure to MC-LR induced epithelial hyperplasia and inflammation, upregulated the expression of matrix metalloproteinases (MMPs) and promoted the migration and invasion of bladder epithelial cells, which provides a basis for further exploring the potential mechanism by which environmental factors increasing the risk of bladder cancer. • Chronic exposure to MC-LR can lead to hyperplasia of bladder epithelial in mice. • MC-LR induces bladder inflammation by activating AKT/NF-kB signaling pathway. • MC-LR upregulates the expression of MMP-9/MMP-2 in the mouse bladder. • MC-LR promotes the migration and invasion of bladder epithelial cells. [ABSTRACT FROM AUTHOR]

High-mobility group box1 (HMGB1) exerts effects on inflammation by binding to receptor for advanced glycation end products (RAGE) or Toll-like receptor 4. Considering that inflammation is involved in pressure overload-induced cardiac hypertrophy, we herein attempted to investigate whether HMGB1 plays a role in myocardial hypertrophy in RAGE knockout mice as well as in the growth and apoptosis of cardiomyocytes. The myocardial expression of RAGE was not significantly changed while TLR4 mRNA was upregulated in response to transverse aortic constriction (TAC) for 1 week. The myocardial expression of HMGB1 protein was markedly increased in TAC group when compared to the sham group. Heart weight to body weight ratio (HW/BW) and lung weight to body weight ratio (LW/BW) were evaluated in RAGE knockout (KO) and wild-type (WT) mice 1 week after TAC. Significant larger HW/BW and LW/BW ratios were found in TAC groups than the corresponding sham groups, but no significant difference was found between KO and WT TAC mice. Similar results were also found when TAC duration was extended to 4 weeks. Cultured neonatal rat cardiomyocytes were treated with different concentrations of recombinant HMGB1, then cell viability was determined using MTT and CCK8 assays and cell apoptosis was determined by Hoechst staining and TUNEL assay. The results came out that HMGB1 exerted no influence on viability or apoptosis of cardiomyocytes. Besides, the protein expression levels of Bax and Bcl2 in response to different concentrations of HMGB1 were similar. These findings indicate that HMGB1 neither exerts influence on cardiac remodeling by binding to RAGE nor induces apoptosis of cardiomyocytes under physiological condition. [ABSTRACT FROM AUTHOR]

Low phosphate (Pi) availability is an important limiting factor affecting soybean production. However, the underlying molecular mechanisms responsible for low Pi stress response and tolerance remain largely unknown, especially for the early signaling events under low Pi stress. Here, a genome-wide transcriptomic analysis in soybean leaves treated with a short-term Pi-deprivation (24 h) was performed through high-throughput RNA sequencing (RNA-seq) technology. A total of 533 loci were found to be differentially expressed in response to Pi deprivation, including 36 mis-annotated loci and 32 novel loci. Among the differentially expressed genes (DEGs), 303 were induced and 230 were repressed by Pi deprivation. To validate the reliability of the RNA-seq data, 18 DEGs were randomly selected and analyzed by quantitative RT-PCR (reverse transcription polymerase chain reaction), which exhibited similar fold changes with RNA-seq. Enrichment analyses showed that 29 GO (Gene Ontology) terms and 8 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were significantly enriched in the up-regulated DEGs and 25 GO terms and 16 KEGG pathways were significantly enriched in the down-regulated DEGs. Some DEGs potentially involved in Pi sensing and signaling were up-regulated by short-term Pi deprivation, including five SPX-containing genes. Some DEGs possibly associated with water and nutrient uptake, hormonal and calcium signaling, protein phosphorylation and dephosphorylation and cell wall modification were affected at the early stage of Pi deprivation. The cis-elements of PHO (phosphatase) element, PHO-like element and P responsive element were present more frequently in promoter regions of up-regulated DEGs compared to that of randomly-selected genes in the soybean genome. Our transcriptomic data showed an intricate network containing transporters, transcription factors, kinases and phosphatases, hormone and calcium signaling components is involved in plant responses to early Pi deprivation. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition. [ABSTRACT FROM AUTHOR]

Early growth response-1 (EGR1) is a multi-domain protein and an immediate early transcription factor that is induced during liver injury and controls the expression of a variety of genes implicated in metabolism, cell proliferation, and tumorigenesis. Liver cancer (LC) is a highly malignant disease with high mortality worldwide. This study focused on the function of EGR1 in LC development and the mechanism of action. Two LC-related datasets GSE101728 and GSE138178 downloaded from the Gene Expression Omnibus (GEO) database were used for identification of key genes involved in cancer progression. A microarray analysis was conducted to identify differentially expressed microRNAs (miRNAs) after EGR1 knockdown. The target gene of miR-675 was identified by integrated analysis. EGR1 and miR-675 were highly expressed, whereas sestrin 3 (SESN3) was poorly expressed in LC tissues and cells. High EGR1 expression was associated with poor liver function and disease severity in patients with LC. Knockdown of EGR1 weakened proliferation and invasiveness of LC cells. EGR1 bound to the miR-675 promoter and increased its transcription, and miR-675 bound to SESN3 mRNA to induce its downregulation. miR-675 upregulation promoted the malignance of LC cells, but further upregulation of SESN3 reduced invasiveness of cells. SESN3 was enriched in the Wnt/β-catenin signaling. EGR1 and miR-675 activated the Wnt/β-catenin through downregulating SESN3. This study demonstrated that EGR1 promotes the malignant behaviors of LC cells through mediating the miRNA-675/SESN3/Wnt/β-catenin axis.

Calcium ion (Ca 2+ ) is a universal second messenger that plays a critical role in plant responses to diverse physiological and environmental stimuli. The stimulus-specific signals are perceived and decoded by a series of Ca 2+ binding proteins serving as Ca 2+ sensors. The majority of Ca 2+ sensors possess the EF-hand motif, a helix-loop-helix structure which forms a turn-loop structure. Although EF-hand proteins in model plant such as Arabidopsis have been well described, the identification, classification, and the physiological functions of EF-hand-containing proteins from soybean are not systemically reported. In this study, a total of at least 262 genes possibly encoding proteins containing one to six EF-hand motifs were identified in soybean genome. These genes include 6 calmodulins (CaMs), 144 calmodulin-like proteins (CMLs), 15 calcineurin B-like proteins, 50 calcium-dependent protein kinases (CDPKs), 13 CDPK-related protein kinases, 2 Ca 2+ - and CaM-dependent protein kinases, 17 respiratory burst oxidase homologs, and 15 unclassified EF-hand proteins. Most of these genes (87.8%) contain at least one kind of hormonal signaling- and/or stress response-related cis -elements in their -1500 bp promoter regions. Expression analyses by exploring the published microarray and Illumina transcriptome sequencing data revealed that the expression of these EF-hand genes were widely detected in different organs of soybean, and nearly half of the total EF-hand genes were responsive to various environmental or nutritional stresses. Quantitative RT-PCR was used to confirm their responsiveness to several stress treatments. To confirm the Ca 2+ -binding ability of these EF-hand proteins, four CMLs (CML1, CML13, CML39, and CML95) were randomly selected for SDS-PAGE mobility-shift assay in the presence and absence of Ca 2+ . Results showed that all of them have the ability to bind Ca 2+ . This study provided the first comprehensive analyses of genes encoding for EF-hand proteins in soybean. Information on the classification, phylogenetic relationships and expression profiles of soybean EF-hand genes in different tissues and under various environmental and nutritional stresses will be helpful for identifying candidates with potential roles in Ca 2+ signal-mediated physiological processes including growth and development, plant-microbe interactions and responses to biotic and abiotic stresses.

Objective: To investigate the clinical value of serum anti-Ku86 in early detection of hepatocellular carcinoma (HCC)., Methods: Expression levels of Ku86 protein in HCC and adjacent normal liver tissues were detected by Western blotting. Serum anti-Ku86 level in 83 patients with early HCC and 124 patients with liver cirrhosis were detected by enzyme-linked immunosorbent assay (ELISA). Chemiluminescence was used to measure the serum level of α-fetoprotein (AFP)., Results: Expression of Ku86 protein in HCC was increased when compared with the adjacent normal liver tissues (0.21 ± 0.05 vs. 0.08 ± 0.02, P < 0.01). Serum anti-Ku86 level was significantly elevated in HCC patients compared with that in liver cirrhosis patients (0.47 ± 0.22 vs. 0.22 ± 0.06 Abs at 450 nm, P < 0.01), but there was no significant difference between HBV infection and HCV infection in HCC patients (0.51 ± 0.19 vs. 0.47 ± 0.24, P = 0.267). Of note, serum anti-Ku86 level was significantly decreased after surgical resection of the tumors in the 30 HCC cases tested (P < 0.01). The results of ROC analysis indicated a better performance of anti-Ku86 (0.857) than AFP (0.739) for early detection of HCC. In 83 HCC patients, the positive rate of anti-Ku86 was 61.4% (51/83), significantly higher than that of the AFP positive rate (27.7%, 23/83). The anti-Ku86 level was positive in 37 of 60 HCC cases with negative AFP. Combination assay of AFP and anti-Ku86 could detect 60 of 83 HCC cases (72.3%, 60/83). There was no significant correlation of anti-Ku86 and AFP (r = 0.156, P = 0.161)., Conclusions: Serum anti-Ku86 level is significantly elevated and is not related to HBV and HCV infection in HCC patients. Serum anti-Ku86 antibody may be a potential biomarker for early detection of HCC, and can be used in combination with AFP in clinics.