A NADPH-Dependent Aldo/Keto Reductase Is Responsible for Detoxifying 3-Keto-Deoxynivalenol to 3-epi-Deoxynivalenol in Pelagibacterium halotolerans ANSP101.

Deoxynivalenol (DON), primarily generated by Fusarium species, often exists in agricultural products. It can be transformed to 3-epi-deoxynivalenol (3-epi-DON), with a relatively low toxicity, via two steps. DDH in Pelagibacterium halotolerans ANSP101 was proved to convert DON to 3-keto-deoxynivalenol (3-keto-DON). In the present research, AKR4, a NADPH-dependent aldo/keto reductase from P. halotolerans ANSP101, was identified to be capable of converting 3-keto-DON into 3-epi-DON. Our results demonstrated that AKR4 is clearly a NADPH-dependent enzyme, for its utilization of NADPH is higher than that of NADH. AKR4 functions at a range of pH 5-10 and temperatures of 20-60 °C. AKR4 is able to degrade 89% of 3-keto-DON in 90 min at pH 7 and 50 °C with NADPH as the cofactor. The discovery of AKR4, serving as an enzyme involved in the final step in DON degradation, might provide an option for the final detoxification of DON in food and feed.

A lasso and random forest model using flow cytometry data identifies primary myelofibrosis.

Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical Philadelphia-Negative (Ph-negative) myeloproliferative neoplasms (MPNs). Differentiating between these types based on morphology and molecular markers is challenging. This study aims to clarify the application of flow cytometry in the diagnosis and differential diagnosis of classical MPNs. This study retrospectively analyzed the immunophenotypes, clinical characteristics, and laboratory findings of 211 Ph-negative MPN patients, including ET, PV, pre-PMF, overt PMF, and 47 controls. Compared to ET and PV, PMF differed in white blood cells, hemoglobin, blast cells in the peripheral blood, abnormal karyotype, and WT1 gene expression. PMF also differed from controls in CD34+ cells, granulocyte phenotype, monocyte phenotype, percentage of plasma cells, and dendritic cells. Notably, the PMF group had a significantly lower plasma cell percentage compared with other groups. A lasso and random forest model select five variables (CD34+CD19+cells and CD34+CD38- cells on CD34+cells, CD13dim+CD11b- cells in granulocytes, CD38str+CD19+/-plasma, and CD123+HLA-DR-basophils), which identify PMF with a sensitivity and specificity of 90%. Simultaneously, a classification and regression tree model was constructed using the percentage of CD34+CD38- on CD34+ cells and platelet counts to distinguish between ET and pre-PMF, with accuracies of 94.3% and 83.9%, respectively. Flow immunophenotyping aids in diagnosing PMF and differentiating between ET and PV. It also helps distinguish pre-PMF from ET and guides treatment decisions.

MsSPL12 is a positive regulator in alfalfa (Medicago sativa L.) salt tolerance.

KEY MESSAGE: Over expression of MsSPL12 improved alfalfa salt tolerance by reducing Na+ accumulation and increasing antioxidant enzyme activity and regulating down-stream gene expression. Improvement of salt tolerance is one of the major goals in alfalfa breeding. Here, we demonstrated that MsSPL12, an alfalfa transcription factor gene highly expressed in the stem cells, plays a positive role in alfalfa salt tolerance. MsSPL12 is localized in the nucleus and shows transcriptional activity in the presence of its C-terminus. To investigate MsSPL12 function in plant response to salt stress, we generated transgenic plants overexpressing either MsSPL12 or a chimeric MsSPL12-SRDX gene that represses the function of MsSPL12 by using the Chimeric REpressor gene-Silencing Technology (CRES-T), and observed that overexpression of MsSPL12 increased the salt tolerance of alfalfa transgenic plants associated with an increase in K+/Na+ ratio and relative water content (RWC) under salt stress treatment, but a reduction in electrolyte leakage (EL), reactive oxygen species (ROS), malondialdehyde (MDA), and proline (Pro) compared to wild type (WT) plants. However, transgenic plants overexpressing MsSPL12-SRDX showed an inhibited plant growth and a reduced salt tolerance. RNA-sequencing and quantitative real-time PCR analyses revealed that MsSPL12 affected the expression of plant abiotic resistance-related genes in multiple physiological pathways. The potential MsSPL12-mediated regulatory pathways based on the differentially expressed genes between the MsSPL12 overexpression transgenics and WT controls were predicted. In summary, our study proves that MsSPL12 is a positive regulator in alfalfa salt tolerance and can be used as a new candidate for manipulation to develop forage crops with enhanced salt tolerance.

Effective Degradation of Free Gossypol in Defatted Cottonseed Meal by Bacterial Laccases: Performance and Toxicity Analysis.

Cottonseed meal (CSM) is the major by-product of the cottonseed oil extraction process with high protein content. However, the presence of free gossypol (FG) in CSM severely restricts its utilization in the food and animal feed industries. The development of a biological strategy for the effective removal of FG in CSM has become an urgent need. In this study, three bacterial laccases including CotA from Bacillus licheniformis, CueO from Escherichia coli, and LcLac from Loigolactobacillus coryniformis were heterologously expressed and investigated for their FG degradation ability. The results showed that CotA laccase displayed the highest FG-degrading capacity among the three laccases, achieving 100% FG degradation at 37 °C and pH 7.0 in 1 h without the addition of a redox mediator. Moreover, in vitro and in vivo studies confirmed that the hepatotoxicity of FG was effectively eliminated after oxidative degradation by CotA laccase. Furthermore, the addition of CotA laccase could achieve 87% to 98% FG degradation in defatted CSM within 2 h. In conclusion, CotA laccase can be developed as an effective biocatalyst for the detoxification of FG in CSM.

Enzymatic characterization and application of soybean hull peroxidase as an efficient and renewable biocatalyst for degradation of zearalenone.

Zearalenone (ZEN) is a notorious mycotoxin commonly found in Fusarium-contaminated crops, which causes great loss in livestock farming and serious health problems to humans. In the present work, we found that crude peroxidase extraction from soybean hulls could use H2O2 as a co-substate to oxidize ZEN. Molecular docking and dynamic simulation also supported that ZEN could bind to the active site of soybean hull peroxidase (SHP). Subsequently, SHP extracted from soybean hulls was purified using a combined purification protocol involving ammonium sulfate precipitation, ion exchange chromatography and size exclusion chromatography. The purified SHP showed wide pH resistance and high thermal stability. This peroxidase could degrade 95 % of ZEN in buffer with stepwise addition of 100 µM H2O2 in 1 h. The two main ZEN degradation products were identified as 13-OH-ZEN and 13-OH-ZEN-quinone. Moreover, SHP-catalyzed ZEN degradation products displayed much less cytotoxicity to human liver cells than ZEN. The application of SHP in various food matrices obtained 54 % to 85 % ZEN degradation. The findings in this study will promote the utilization of SHP as a cheap and renewable biocatalyst for degrading ZEN in food.

Cholesterol lowering in diet-induced hypercholesterolemic mice using Lactobacillus bile salt hydrolases with different substrate specificities.

The cholesterol-lowering effect of lactic acid bacteria with high activity of bile salt hydrolase (BSH) is unclear. We believe that distinguishing BSH substrate specificity is necessary to study the effect of various BSH enzymes. We engineered a BSH mutant enzyme recombinant strain named F67A, which exclusively hydrolyzes taurocholic acid (TCA) using site-directed mutagenesis, and a previously lab-constructed BSH recombinant strain, YB81 that exclusively hydrolyzes glycocholic acid (GCA). We also constructed the recombinant strain named NB5462, which carries the empty pSIP411 plasmid and was used as a blank control strain. The intestinal flora in pseudo-germ-free (PGF) mice in which intestinal flora were eliminated via antibiotics, and F67A successfully reduced serum cholesterol levels in high-cholesterol diet-fed mice, whereas YB81 did not yield the same results. However, YB81 regained its cholesterol-lowering capacity in specific pathogen-free (SPF) mice with intact intestinal flora. The cholesterol-lowering mechanism of F67A involved modifying the bile acid pool through BSH enzyme activity. This adjustment regulated the expression of intestinal farnesoid X receptor and subsequently elevated hepatic cholesterol 7α-hydroxylase (CYP7A1), effectively reducing cholesterol levels. Conversely, GCA, the substrate of YB81, was found in minimal quantities in mice, preventing it from inducing changes in bile acid pools. In the presence of intestinal flora, the YB81 BSH enzyme induced notable alterations in bile acids by regulating changes in the intestinal flora and BSH within the flora, ultimately resulting in cholesterol reduction. This is the first study investigating the substrate specificity of BSH, demonstrating that different substrate-specific BSH enzymes exhibit cholesterol-lowering properties. Additionally, we elaborate on the mechanism of BSH-mediated enterohepatic axis regulation.

Improvement of aflatoxin B1 degradation ability by Bacillus licheniformis CotA-laccase Q441A mutant.

Aflatoxin B1 (AFB1) contamination seriously threatens nutritional safety and common health. Bacterial CotA-laccases have great potential to degrade AFB1 without redox mediators. However, CotA-laccases are limited because of the low catalytic activity as the spore-bound nature. The AFB1 degradation ability of CotA-laccase from Bacillus licheniformis ANSB821 has been reported by a previous study in our laboratory. In this study, a Q441A mutant was constructed to enhance the activity of CotA-laccase to degrade AFB1. After the site-directed mutation, the mutant Q441A showed a 1.73-fold higher catalytic efficiency (kcat/Km) towards AFB1 than the wild-type CotA-laccase did. The degradation rate of AFB1 by Q441A mutant was higher than that by wild-type CotA-laccase in the pH range from 5.0 to 9.0. In addition, the thermostability was improved after mutation. Based on the structure analysis of CotA-laccase, the higher catalytic efficiency of Q441A for AFB1 may be due to the smaller steric hindrance of Ala441 than Gln441. This is the first research to enhance the degradation efficiency of AFB1 by CotA-laccase with site-directed mutagenesis. In summary, the mutant Q441A will be a suitable candidate for highly effective detoxification of AFB1 in the future.

Prognostic significance of the frequencies of bone marrow lymphocyte subsets in adult acute myeloid leukemia at diagnosis.

INTRODUCTION: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited. METHODS: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4+ T, CD8+ T, γδT, NK, and B cell frequencies using multi-parameter flow cytometry. RESULTS: Low frequencies of lymphocytes, T, CD4+ T, and CD8+ T cells were associated with significantly lower rates of one-course complete remission (CR) (all p < 0.05). Moreover, the frequency of CD4+ T cells independently predicted one-course CR achievement (p = 0.021). Low frequencies of T and CD8+ T cells were significantly associated with lower relapse-free survival (RFS) rates (p = 0.032; 0.034), respectively, and a low frequency of CD8+ T cells was associated with a significantly lower overall survival (OS) rate (p = 0.028). Combination of frequency of CD8+ T cells and ELN risk stratification showed that patients with ELN-intermediate/adverse risk + high CD8+ T cell frequency had a similar RFS rate to those with ELN-favorable risk + high CD8+ T cell frequency and those with ELN-favorable risk + low CD8+ T cell frequency (p = 0.88; 0.76), respectively. The RFS rate of patients with ELN intermediate/adverse risk + low CD8+ T cell frequency was significantly lower than that of all aforementioned patients (p = 0.021; 0.0007; 0.028), respectively. CONCLUSION: The frequencies of BM lymphocyte subsets at diagnosis predicted clinical outcomes and could help improve risk stratification in AML.

Identification of an optimized glycolytic-related risk signature for predicting the prognosis in breast cancer using integrated bioinformatic analysis.

Aberrant metabolic disorders and significant glycolytic alterations in tumor tissues and cells are hallmarks of breast cancer (BC) progression. This study aims to elucidate the key biomarkers and pathways mediating abnormal glycolysis in breast cancer using bioinformatics analysis. Differential genes expression analysis, gene ontology analysis, Kyoto encyclopedia of genes and genomes analysis, gene set enrichment analyses, and correlation analysis were performed to explore the expression and prognostic implications of glycolysis-related genes. We effectively integrated 4 genes to construct a prognostic model of shorter survival in the high-risk versus low-risk group. The prognostic model showed promising predictive value and may be an integral part of the prognosis of BC. The survival analysis and receiver operating characteristic curves suggested that the signature showed a good predictive performance in both the The Cancer Genome Atlas training set and 2 gene expression omnibus validation sets. Multivariable analysis demonstrated that the 4-gene signature had an independent prognostic value. Furthermore, all calibration curves exhibited robust validity in prognostic prediction. We established an optimized 4-gene signature to clarify the connection between glycolysis and BC, and offered an attractive platform for risk stratification and prognosis predication of BC patients.

Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.

Yeast polysaccharide mitigated oxidative injury in broilers induced by mixed mycotoxins via regulating intestinal mucosal oxidative stress and hepatic metabolic enzymes.

This study was aimed to investigate the effects of yeast polysaccharides (YPS) on growth performance, intestinal health, and aflatoxin metabolism in livers of broilers fed diets naturally contaminated with mixed mycotoxins (MYCO). A total of 480 one-day-old Arbor Acre male broilers were randomly allocated into a 2 × 3 factorial arrangement of treatments (8 replicates with 10 birds per replicate) for 6 wk to assess the effects of 3 levels of YPS (0, 1, or 2 g/kg) on the broilers fed diets contaminated with or without MYCO (95 µg/kg aflatoxin B1, 1.5 mg/kg deoxynivalenol, and 490 µg/kg zearalenone). Results showed that mycotoxins contaminated diets led to significant increments in serum malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, mRNA expressions of TLR4 and 4EBP1 associated with oxidative stress, mRNA expressions of CYP1A1, CYP1A2, CYP2A6, and CYP3A4 associated with hepatic phase Ⅰ metabolizing enzymes, mRNA expressions of p53 associated with hepatic mitochondrial apoptosis, and AFB1 residues in the liver (P < 0.05); meanwhile dietary MYCO decreased the jejunal villus height (VH), villus height/crypt depth (VH/CD), the activity of serum total antioxidant capacity (T-AOC), mRNA expressions of jejunal HIF-1α, HMOX, and XDH associated with oxidative stress, mRNA expressions of jejunal CLDN1, ZO1, and ZO2, and mRNA expression of GST associated with hepatic phase Ⅱ metabolizing enzymes of broilers (P < 0.05). Notably, the adverse effects induced by MYCO on broilers were mitigated by supplementation with YPS. Dietary YPS supplementation reduced the concentrations of serum MDA and 8-OHdG, jejunal CD, mRNA expression of jejunal TLR2, and 4EBP1, hepatic CYP1A2, and p53, and the AFB1 residues in the liver (P < 0.05), and elevated the serum T-AOC and SOD, jejunal VH, and VH/CD, and mRNA expression of jejunal XDH, hepatic GST of broilers (P < 0.05). There were significant interactions between MYCO and YPS levels on the growth performance (BW, ADFI, ADG, and F/G) at d 1 to 21, d 22 to 42, and d 1 to 42, serum GSH-Px activity, and mRNA expression of jejunal CLDN2 and hepatic ras of broilers (P < 0.05). In contrast with MYCO group, the addition of YPS increased BW, ADFI, and ADG, the serum GSH-Px activity (14.31%-46.92%), mRNA levels of jejunal CLDN2 (94.39%-103.02%), decreased F/G, and mRNA levels of hepatic ras (57.83%-63.62%) of broilers (P < 0.05). In conclusion, dietary supplements with YPS protected broilers from mixed mycotoxins toxicities meanwhile keeping normal performance of broilers, presumably via reducing intestinal oxidative stress, protecting intestinal structural integrity, and improving hepatic metabolic enzymes to minimize the AFB1 residue in the liver and enhance the performance of broilers.

Genome-wide identification and analysis of TCP family genes in Medicago sativa reveal their critical roles in Na+/K+ homeostasis.

BACKGROUND: Medicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis. RESULTS: Seventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 µM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. CONCLUSIONS: We systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.

Effects of myonectin on porcine intramuscular adipocyte differentiation and exogenous free fatty acid utilization.

As an important factor secreted by skeletal muscle, myonectin can regulate lipid metabolism and energy metabolism, but its role in the utilization of peripheral free fatty acids (FFAs) by porcine intramuscular fat cells remains to be further investigated. In this study, porcine intramuscular adipocytes were treated with recombinant myonectin and palmitic acid (PA), either alone or in combination, and then were examined for their uptake of exogenous FFAs, intracellular lipid synthesis and catabolism, and mitochondrial oxidation of fatty acids. The results showed that myonectin decreased the area of lipid droplets in intramuscular adipocytes (p < 0.05) and significantly increased (p < 0.05) the expression levels of hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). Moreover, myonectin can up-regulate the expression of p38 mitogen-activated protein kinase (p38 MAPK). Myonectin significantly promoted the uptake of peripheral FFAs (p < 0.01), improved (p < 0.05) the expression of fatty transport protein 1 (FATP1) and fatty acid binding protein 4 (FABP4) in intramuscular adipocytes. Myonectin also significantly increased (p < 0.05) the expression levels of fatty acid oxidation markers: transcription factor (TFAM), uncoupling protein-2 (UCP2) and oxidative respiratory chain marker protein complex I (NADH-CoQ) in mitochondria of intramuscular adipocytes. In summary, myonectin promoted the absorption, transport, and oxidative metabolism of exogenous FFAs in mitochondria, thereby inhibiting lipid deposition in porcine intramuscular adipocytes.

A Robust Squarate-Cobalt Metal-Organic Framework for CO2/N2 Separation.

The separation of CO2 from the industrial post-combustion flue gas is of great importance to reduce the increasingly serious greenhouse effect, yet highly challenging due to the extremely high stability, low cost, and high separation performance requirements for adsorbents under the practical operating conditions. Herein, we report a robust squarate-cobalt metal-organic framework (MOF), FJUT-3, featuring an ultra-small 1D square channel decorated with -OH groups, for CO2/N2 separation. Remarkably, FJUT-3 not only has excellent stability under harsh chemical conditions but also presents low-cost property for scale-up synthesis. Moreover, FJUT-3 shows excellent CO2 separation performance under various humid and temperature conditions confirmed by the transient breakthrough experiments, thus enabling FJUT-3 with adequate potentials for industrial CO2 capture and removal. The distinct CO2 adsorption mechanism is well elucidated by theoretical calculations, in which the hierarchical C···OCO2, C-O···CCO2, and O-H···OCO2 interactions play a vital synergistic role in the selective CO2 adsorption process.

Effects of isolated central nervous system involvement evaluated by multiparameter flow cytometry prior to allografting on outcomes of patients with acute lymphoblastic leukemia.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major strategy to cure patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate whether isolated flow cytometry (FCM)-positive central nervous system (CNS) involvement before allo-HSCT is clinically significant. Methods: The effects of isolated FCM-positive CNS involvement prior to transplantation on the outcomes of 1406 ALL patients with complete remission (CR) were retrospectively investigated. Results: Patients were classified into isolated FCM-positive CNS involvement (n=31), cytology-positive CNS involvement (n = 43), and negative CNS involvement (n = 1332) groups. Among the three groups, the 5-year cumulative incidence of relapse (CIR) values were 42.3%, 48.8%, and 23.4%, respectively (P<0.001). The 5-year leukemia-free survival (LFS) values were 44.7%, 34.9%, and 60.8%, respectively (P<0.001). Compared with the negative CNS group (n=1332), the 5-year CIR of the pre-HSCT CNS involvement group (n=74) was higher (46.3% vs. 23.4%, P<0.001], and the 5-year LFS was inferior (39.1% vs. 60.8%, P<0.001). Multivariate analysis indicated that four variables, T-cell ALL, in second complete remission or beyond (CR2+) at HSCT, pre-HSCT measurable residual disease positivity, and pre-HSCT CNS involvement, were independently associated with a higher CIR and inferior LFS. A new scoring system was developed using the following four variables: low-risk, intermediate-risk, high-risk, and extremely high-risk groups. The 5-year CIR values were 16.9%, 27.8%, 50.9%, and 66.7%, respectively (P<0.001), while the 5-year LFS values were 67.6%, 56.9%, 31.0%, and 13.3%, respectively (P<0.001). Conclusion: Our results suggest that ALL patients with isolated FCM-positive CNS involvement are at a higher risk of recurrence after transplantation. Patients with pre-HSCT CNS involvement had higher CIR and inferior survival outcomes.

Association between the expression levels of ADAMTS16 and BMP2 and tumor budding in hepatocellular carcinoma.

Tumor budding (TB) has become a crucial factor for predicting the malignancy grade and prognostic outcome for multiple types of solid cancer. Studies have investigated the prognostic value of TB in hepatocellular carcinoma (HCC). However, its molecular mechanism in HCC remains unclear. To the best of our knowledge, the present study was the first to compare the expression of differentially expressed genes (DEGs) between TB-positive (TB-pos) and TB-negative HCC tissues. In the present study, total RNA was extracted from 40 HCC tissue specimens and then sequenced. According to Gene Ontology (GO) functional annotation, upregulated DEGs were markedly associated with embryonic kidney development-related GO terms, which suggested that the TB process may at least partly mimic the process of embryonic kidney development. Subsequently, two genes, a disintegrin and metalloproteinase domain with thrombospondin motifs 16 (ADAMTS16) and bone morphogenetic protein 2 (BMP2), were screened and verified through immunohistochemical analysis of HCC tissue microarrays. According to the immunohistochemical results, ADAMTS16 and BMP2 were upregulated in TB-pos HCC samples, and BMP2 expression was increased in budding cells compared with the tumor center. Additionally, through cell culture experiments, it was demonstrated that ADAMTS16 and BMP2 may promote TB of liver cancer, thus promoting the malignant progression of liver cancer. Further analysis revealed that ADAMTS16 expression was associated with necrosis and cholestasis, and BMP2 expression was associated with the Barcelona Clinic Liver Cancer stage and the vessels encapsulating tumor clusters. Overall, the findings of the present study provided insights into the possible mechanisms of TB in HCC and revealed potential anti-HCC therapeutic targets.

CSRP2 transcript levels after consolidation therapy increase prognostic prediction ability in B-cell acute lymphoblastic leukaemia.

Quantification of measurable residual disease (MRD) correlates with the risk of leukemia recurrence in adults with B-cell acute lymphoblastic leukemia (ALL). However, it remains unknown whether collecting data on cysteine and glycine-rich protein 2 (CSRP2) transcript levels, after completing the second course of consolidation, improves prognosis prediction accuracy. A total of 204 subjects with B-cell ALL were tested for CSPR2 transcripts after completing the second course of consolidation using quantitative real-time polymerase chain reaction (qRT-PCR) and divided into high (N = 32) and low (N = 172) CSRP2 expression cohorts. In multivariable analyses, subjects with high expression of CSRP2 had a higher 5-year cumulative incidence of relapse (CIR) (hazard ratio [HR] = 2.57, 95% confidence interval [CI] 1.38-4.76; P = 0.003), lower 5-year relapse-free survival (RFS) (HR = 3.22, 95% CI 1.75-5.93; P < 0.001), and overall survival (OS) (HR = 4.59, 95% CI 2.64-7.99; P < 0.001) in the whole cohort, as well as in the multi-parameter flow cytometry (MPFC) MRD-negative cohort (for CIR, HR = 2.70, 95% CI 1.19-6.12; for RFS, HR = 4.37, 95% CI 1.94-9.85; for OS, HR = 4.90, 95% CI 2.43-9.90; all P < 0.05). Prognostic analysis showed that allogeneic hematopoietic stem cell transplantation (allo-HSCT) could significantly improve the prognosis of patients with high CSRP2 expression (allo-HSCT vs chemotherapy: 5-year CIR, 52% vs 91%; RFS, 41% vs 9%; OS, 38% vs 20%; all P < 0.05). Our data indicate that incorporating data from CSPR2 transcript levels to the MRD-testing at the end of the second course of consolidation therapy enhances prognosis prediction accuracy in adults with B-cell ALL.

Personality traits and occupational status-evidence from China.

This paper estimates the relationship between personality traits measured by the "Big Five Model" and occupational status with a nationally representative household survey from China. I find that four of the five personality traits except extraversion are significantly associated with occupational status in terms of occupational choices, occupational prestige, and socioeconomic status. In particular, conscientiousness is the most important predictor among the five dimensions of personality traits. The findings also suggest that the returns of personality traits to occupational status are higher for females.

Enhanced Electrochemical Nitrate-to-Ammonia Performance of Cobalt Oxide by Protic Ionic Liquid Modification.

Electrochemical conversion of nitrate to ammonia is an appealing way for small-scale and decentralized ammonia synthesis and waste nitrate treatment. Currently, strategies to enhance the reaction performance through elaborate catalyst design have been well developed, but it is still of challenge to realize the promotion of reactivity and selectivity at the same time. Instead, a facile method of catalyst modification with ionic liquid to modulate the electrode surface microenvironment that mimic the role of the natural MoFe protein environment is found effective for the simultaneous improvement of NH3 yield rate and Faradaic efficiency (FE) at a low NaNO3 concentration of 500 ppm. Protic ionic liquid (PIL) N-butylimidazolium bis(trifluoromethylsulfonyl)imide ([Bim]NTf2 ) modified Co3 O4-x is fabricated and affords the NH3 yield rate and FE of 30.23±4.97 mg h-1 mgcat. -1 and 84.74±3.43 % at -1.71 and -1.41 V vs. Ag/AgCl, respectively, outperforming the pristine Co3 O4-x . Mechanistic and theoretical studies reveal that the PIL modification facilitates the adsorption and activation of NO3 - as well as the NO3 - -to-NH3 conversion and inhibits hydrogen evolution reaction competition via enhancing the Lewis acidity of the Co center, shuttling protons, and constructing a hydrogen bonded and hydrophobic electrode surface microenvironment.