CircZBTB46 predicts poor prognosis and promotes disease progression of myelodysplastic syndromes and acute myeloid leukemia.

Circular RNAs (circRNAs) have been recently identified as important regulators of various diseases, especially cancer. However, the roles of circRNAs in hematologic malignancies have been rarely reported. This study aimed to identify a specific circRNA expression profile in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to evaluate the biological roles of circRNA in MDS and AML for understanding their clinical significance. Reverse transcription-quantitative PCR was performed to validate the expression of circZBTB46. Kruskal-Wallis test, Kaplan-Meier curves, and the Cox regression model were employed to analyze the clinical significance of circZBTB46. Two specific shRNAs as well as an expression lentiviral vector of circZBTB46 were constructed to identify the biological function of circZBTB46. The impact of circZBTB46 on leukemia cell proliferation, cell cycle distribution, and apoptosis was confirmed using cell viability assay and flow cytometry analysis. The expression of circZBTB46 gradually increased in patients with higher-risk MDS and AML, as compared to controls. CircZBTB46 expression was significantly correlated with important clinical parameters of MDS, including WHO classification, absolute neutrophil count (ANC), marrow blast, IPSS karyotype, IPSS/IPSS-R risk groups, and AML transformation. CircZBTB46 expression was also associated with ANC, marrow blast, cytogenetic risk groups, FLT3-ITD mutation, and treatment response in AML patients. Furthermore, circZBTB46 overexpression was significantly correlated with shorter overall survival (OS, P = 0.0342, median survival time 18.5 vs. 45.4 months) and leukemia-free survival (LFS, P = 0.0421) in MDS, also with the shorter OS in AML (P = 0.0293, median survival time 11.6 vs. 16.9 months). Functional studies revealed that silencing circZBTB46 expression significantly inhibited proliferation and induced apoptosis in SKM-1, THP-1, and K562 cell lines, while rescue experiments alleviated the siRNA-mediated growth inhibition and apoptosis in these leukemic cells. The present data suggested the essential oncogenic role of circZBTB46, as a progression and survival indicator in both MDS and AML.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence.

Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.

Dielectric barrier discharge plasma for the remediation of microplastic-contaminated soil from landfill.

The huge amount of plastic waste accumulated in landfills has caused serious microplastic (MP) pollution to the soil environment, which has become an urgent issue in recent years. It is challenging to deal with the non-biodegradable MP pollutants in actual soil from landfills. In this study, a coaxial dielectric barrier discharge (DBD) system was proposed to remediate actual MP-contaminated landfill soil due to its strong oxidation capacity. The influence of carrier gas type, applied voltage, and air flow rate was investigated, and the possible degradation pathways of MP pollutants were suggested. Results showed the landfill soil samples contained four common MP pollutants, including polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyvinyl chloride (PVC) with sizes ranging from 50 to 1500 µm. The MP pollutants in the soil were rapidly removed under the action of reactive oxygen species (ROS) generated by DBD plasma. Under the air flow rate of 1500 mL min-1, the maximum remediation efficiency represented by mass loss reached 96.5% after 30 min treatment. Compared with nitrogen, when air was used as the carrier gas, the remediation efficiency increased from 41.4% to 81.6%. The increased applied voltage from 17.5 to 24.1 kV could also promote the removal of MP contaminants. Sufficient air supply was conducive to thorough removal. However, when the air flow rate reached 1500 mL min-1 and continued to rise, the final remediation efficiency would be reduced due to the shortened residence time of ROS. The DBD plasma treatment proposed in this study showed high energy efficiency (19.03 mg kJ-1) and remediation performance (96.5%). The results are instructive for solving MP pollution in the soil environment.

[Corrigendum] Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

Subsequently to the publication of the above article, and a Corrigendum that has already been published with the intention of showing corrected versions of Figs. 1 and 8 (DOI: 10.3892/or.2022.8348; published online on June 14, 2022), the authors have belatedly realized that the revisions made to Fig. 8 necessitated changes that should have been introduced into Fig. 9, although these were not attended to in the first corrigendum. Essentially, Fig. 8 was revised as the cell apoptosis and cell proliferation assays therein were poorly presented, which made the interpretation of the data difficult; Fig. 9 showed the fractions of apoptotic cells in the SKM­1 and THP­1 cell lines with lncENST00000444102 overexpression as this pertained to Fig. 8. A revised version of Fig. 9, presenting the analysis of the data shown in the revised version of Fig. 8, is shown opposite. In addition to the revision of Fig. 9, the sentence starting on p. 517, left­hand column, line 12 ["The flow cytometric apoptosis assay revealed that lncENST00000444102 overexpression promoted tumor cells to undergo apoptosis compared to control cells (P<0.001, Fig. 9)"] should be replaced with the following text, to reflect the change in the level of statistical significance: 'The flow cytometric apoptosis assay revealed that lncENST00000444102 overexpression promoted tumor cells to undergo apoptosis compared to control cells (P<0.01, Fig. 9)". Note that the revisions made to Figs. 8 and 9 in this paper have not had a major impact on the reported results, and do not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this additional Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 42: 509­520, 2019; DOI: 10.3892/or.2019.7175].

Effect of iron supplementation on platelet count in adult patients with iron deficiency anemia.

Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis.The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 109/L. With baseline platelet counts>450 × 109 /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 109/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 109/L).Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (P < .05). From baseline to 8 weeks of continuous iron supplementation treatment, the mean platelet counts in both groups were decreased at 2-week treatment intervals. And in the IDA with thrombocytosis group, half of the patients resolved thrombocytosis after 2 weeks of iron supplementation, and the counts of all patients with thrombocytosis decreased below 450 × 109 /L within 6 weeks.In conclusion, the rate of reactive thrombocytosis in patients with IDA was 8.1%. IDA patients with thrombocytosis showed more severe anemia, lower ferritin, and more advanced iron deficiency than those without thrombocytosis. Platelet counts of half of the patients with thrombocytosis reduced below cut off of 450 × 109/L for thrombocytosis after 2 weeks of treatment, and all patients resolved thrombocytosis after 6 weeks. Our study provided clinical evidence for more effective and individualized iron management in the future. IDA patients with thrombocytosis should take active iron treatment and increase follow-up frequency to prevent thrombotic events. For patients with persistent thrombocytosis, a concomitant clonal process should be considered.

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling.

The factors that affect hypomethylating agents (HMAs) sensitivity in myelodysplastic syndrome (MDS) are complex and multifaceted. They include DNA methylation, gene expression, mutation, etc. However, the underlying mechanisms are still not clearly illustrated. In the present work, ABAT gene expression was associated with HMAs sensitivity. It was found that ABAT gene interference increased the sensitivity of HL-60 and THP-1 cells to HMAs treatment, while ABAT overexpression decreased its sensitivity. RNA-sequencing analysis showed that ABAT knockdown activated both interferon I and interferon-gamma signaling while inhibiting the secondary metabolic synthesis and arginine metabolic process. Gas chromatography-mass spectrometry (GC-MS) based metabolic profiling also demonstrated that ABAT gene knockdown affected arginine, alanine, aspartate, and glutamate metabolism, in addition to the biosynthesis of valine, leucine, and isoleucine, and the metabolism of beta-alanine. The ABAT gene expression downregulation could activate the CXCR4/mTOR signaling pathway, which was related to HMAs sensitivity. CXCR4 expression was regulated by mTOR activity and vice versa. In vivo, mice injected with ABAT gene knockdown cells lived longer than control mice after HMAs treatment. Overall, this study elucidates the novel regulatory mechanisms of HMAs sensitivity and provides a potential therapeutic target in MDS.

[Corrigendum] Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

Following the publication of the above paper, the authors have realized that the cell apoptosis and cell proliferation assays in Fig. 8 were poorly presented, which made the interpretation of the data difficult. Furthermore, a change was also required to the text concerning the description of Fig. 8: The sentence starting on p. 517, left­hand column, line 7 ('The fraction of apoptotic cells was 22.41±2.596 in the lncENST00000444102-overexpressing SKM­1 cells, and 8.650±0.889 in the negative control; the fraction of apoptotic cells was 20.58±2.190 in the lncENST00000444102­overexpressing THP­1 cells and 8.192±0.997 in the negative control group (P<0.001, Fig. 8B)' should be replaced with the following text: 'Flow cytometry showed that the fraction of apoptotic cells increased in the lncENST00000444102­overexpressing SKM­1 and THP­1 cells, as determined by Annexin V­APC/7-AAD staining at 48 h (P<0.05; Fig. 8B)'. A revised version of Fig. 8, presenting the results of the flow cytometric analysis more clearly, is shown on the next page. Note that the revisions made to this figure have not had a major impact on the reported results, and do not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 42: 509­520, 2019; DOI: 10.3892/or.2019.7175].

Synthesis of Microporosity Dominant Wood-Based Activated Carbon Fiber for Removal of Copper Ions.

Steam activation treatments were introduced in the preparation of activated carbon fiber from liquefied wood (LWACF), to enlarge its specific surface area and develop the pore size distribution. With increasing activation time, the average fiber diameter of LWACF decreased from 27.2 µm to 13.2 µm, while the specific surface area increased from 1025 to 2478 m2/g. Steam activation predominantly enhanced the development of microporosity, without significant pore widening. Prolonging the steam activation time exponentially increased the removal efficiency of Cu2+ at a constant adsorbent dose, as a result of an increase in the number of micropores and acidic-oxygenated groups. Moreover, for LWACF activated for 220 min at 800 °C, the removal efficiency of Cu2+ increased from 55.2% to 99.4%, when the porous carbon fiber dose went from 0.1 to 0.5 g/L. The synthesized LWACF was proven to be a highly efficient adsorbent for the treatment of Cu2+ ion-contaminated wastewater.

Computed Tomography-Based Radiomic Analysis for Preoperatively Predicting the Macrovesicular Steatosis Grade in Cadaveric Donor Liver Transplantation.

This study is aimed at determining the ability of computed tomography- (CT-) based radiomic analysis to distinguish between grade 0/1 and grade 2/3 macrovesicular steatosis (MaS) in cadaveric donor liver transplantation cases. Preoperative noncontrast-enhanced CT images of 150 patients with biopsy-confirmed MaS were analyzed retrospectively; these patients were classified into the low-grade MaS (n = 100, grade 0 or 1) and high-grade MaS (n = 50, grade 2 or 3) groups. Three-dimensional spherical regions of interest of 40 pixel (2.5 cm) in diameter were placed in the right anterior and left lateral segments of the liver. Thereafter, 300 regions of interest (ROIs) were segmented and randomly assigned to the training and testing groups at a ratio of 7 : 3. A total of 402 radiomic features were extracted from each ROI. For MaS classification, a radiomic model was established using multivariate logistic regression analysis. Clinical data, including age, sex, and liver function, were collected to establish the clinical model at the patient level. The performances of the radiomic and clinical models, i.e., the diagnostic discrimination, calibration, and clinical utilities, were evaluated. The radiomic model, with seven selected features, depicted a good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.907 (95% confidence interval (CI): 0.869-0.940) in the training cohort and 0.906 (95% CI: 0.843-0.959) in the testing cohort. The calibration curve revealed good agreement between the predicted and observed probabilities in the training and testing cohorts (both P > 0.05 in the H-L test). Decision curve analysis revealed that the radiomic model was more beneficial than the treat-all or treat-none schemes for predicting the MaS grade. Alanine transaminase and gamma-glutamyl transferase were used for building the clinical model, and the AUC was 0.784 in the total cohort. The CT-based radiomic model outperforming the conventional clinical model could provide an important reference for MaS grading in cadaveric liver donors.

Causes of PM2.5 pollution in an air pollution transport channel city of northern China.

To develop effective mitigation policies, a comprehensive understanding of the evolution of the chemical composition, formation mechanisms, and the contribution of sources at different pollution levels is required. PM2.5 samples were collected for 1 year from August 2016 to August 2017 at an urban site in Zibo, then chemical compositions were analyzed. Secondary inorganic aerosols (SNA), anthropogenic minerals (MIN), and organic matter (OM) were the most abundant components of PM2.5, but only the mass fraction of SNA increased as the pollution evolved, implying that PM2.5 pollution was caused by the formation of secondary aerosols, especially nitrate. A more intense secondary transformation was found in the heating season (from November 15, 2016, to March 14, 2017), and a faster secondary conversion of nitrate than sulfate was discovered as the pollution level increased. The formation of sulfate was dominated by heterogeneous reactions. High relative humidity (RH) in polluted periods accelerated the formation of sulfate, and high temperature in the non-heating season also promoted the formation of sulfate. Zibo city was under ammonium-rich conditions during polluted periods in both seasons; therefore, nitrate was mainly formed through homogeneous reactions. The liquid water content increased significantly as the pollution levels increased when the RH was above 80%, indicating that the hygroscopic growth of aerosol aggravated the PM2.5 pollution. Source apportionment showed that PM2.5 was mainly from secondary aerosol formation, road dust, coal combustion, and vehicle emissions, contributing 36.6%, 16.5%, 14.7%, and 13.1% of PM2.5 mass, respectively. The contribution of secondary aerosol formation increased remarkably with the deterioration of air quality, especially in the heating season.

Resistance to Hypomethylating Agents in Myelodysplastic Syndrome and Acute Myeloid Leukemia From Clinical Data and Molecular Mechanism.

The nucleoside analogs decitabine (5-AZA-dC) and azacitidine (5-AZA) have been developed as targeted therapies to reverse DNA methylation in different cancer types, and they significantly improve the survival of patients who are not suitable for traditional intensive chemotherapies or other treatment regimens. However, approximately 50% of patients have a response to hypomethylating agents (HMAs), and many patients have no response originally or in the process of treatment. Even though new combination regimens have been tested to overcome the resistance to 5-AZA-dC or 5-AZA, only a small proportion of patients benefited from these strategies, and the outcome was very poor. However, the mechanisms of the resistance remain unknown. Some studies only partially described management after failure and the mechanisms of resistance. Herein, we will review the clinical and molecular signatures of the HMA response, alternative treatment after failure, and the causes of resistance in hematological malignancies.

Pollution Assessment of Potentially Toxic Elements (PTEs) in Soils around the Yanzhuang Gold Mine Tailings Pond, Pinggu County, Beijing, China.

The accumulation of tailings from gold mining and smelting may result in PTE pollution. We investigated PTE contamination from a large amalgamated gold mine tailings pond in Pinggu County, Beijing. In November 2017, 30 soil samples were collected around the tailings pond. The concentrations and pollution degree of PTEs in the samples and the sources of Sb, As, Cd, Cu, Pb, Zn and Hg were analyzed. The average concentration of these elements in soil samples near the tailings pond (16.24, 28.29, 0.99, 171.04, 263.25, 99.73, 0.72 mg/kg, respectively) were higher than their corresponding standard values and background values of the study area. The geoaccumulation index showed that the pollution degree of As, Pb and Hg was moderate, while Sb and Cu present non-pollution to moderate pollution. The average EF values of the elements were Sb (38.31), As (4.23), Cd (0.71), Cu (3.68), Pb (21.24), Zn (0.82) and Hg (5.29), respectively. The environmental risk assessment developed throughout the PERI method indicated that Sb, As, Hg and Pb were the main pollutants in the study area. The three quantitative risk indicators (RI, Igeo and EF) were positively correlated, and all of them indicated that PTEs had significant pollution to the local area. Thus, Sb, As, Pb, Cu, and Hg pollution should be highly concerning. Multivariate statistical analysis shows that the pollution of PTEs was mainly caused by the accumulation of tailings ponds after gold mining and smelting. The research result is of great significance for the prevention and control of soil pollution of PTEs near the tailings pond.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

Fabrication and Characterization of Activated Carbon Fibers from Oil Palm Trunk.

To develop more valuable application, oil palm trunk was successfully converted into activated carbon fibers (ACFs). An effective process of chemical treatment with dilute sulfuric acid was conducted to improve the thermal stability of primary fibers for further heating treatment. Carbon dioxide (CO2) was used as activator to produce much porous structure with various pore diameter. The specific surface area (SBET) and total pore volume (Vtotal) of resultant ACFs showed increasing trend as rise of activation temperature and time. The ACFs obtained under the temperature of 900 °C and time of 90 min exhibited highest SBET and Vtotal, which were more than 1800 m2/g and 0.7 mL/g, respectively. Meanwhile, more graphic carbon on the surface of ACFs were destroyed with prolonging activation time, resulting in the oxygen-containing functional groups formed during activation process with CO2. Due to the abundant pores and surface functional groups, the ACFs exhibited excellent adsorption capacity of chromium and would be an alternative material for industrial adsorption utilization.

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Importance: It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective: To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants: This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions: Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures: The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results: Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance: Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration: ClinicalTrials.gov Identifier: NCT02631668.

LOC101928834, a novel lncRNA in Wnt/ß-catenin signaling pathway, promotes cell proliferation and predicts poor clinical outcome in myelodysplastic syndromes.

Long non-coding RNAs (lncRNAs) play important roles in hematological malignancies. We have previously identified several differentially expressed lncRNAs in myelodysplastic syndromes (MDS) by microarray analysis. In the present study, we explored the regulatory circuitry, potential functions, clinical and prognostic relevance of these lncRNAs in MDS by developing a lncRNA regulation network. We identified a novel lncRNA, LOC101928834, which was significantly up-regulated in the bone marrow of patients with MDS and acute myeloid leukemia (AML). We further evaluated the clinical relevance of LOC101928834 in 89 MDS and 110 AML patients and found that higher level of LOC101928834 expression was associated with higher white blood cell count, higher blast percentage, the subtype of refractory cytopenia with excess blasts (RAEB) and shorter overall survival in MDS patients. Receiver operating characteristic (ROC) curve analysis showed that LOC101928834 expression could discriminate MDS-RAEB patients from control with an area under the receiver-operating curve (AUC) of 0.9048. Moreover, functional analysis showed that LOC101928834 promoted cell proliferation and cell cycle progression, and activated Wnt/ß-catenin signaling pathway in vitro. In conclusion, LOC101928834 expression is correlated with clinical and biological features of MDS and may serve as a novel diagnostic and prognostic biomarker.

Hematopoietic Stem and Progenitor Cells Exhibit Stage-Specific Translational Programs via mTOR- and CDK1-Dependent Mechanisms.

Hematopoietic stem cells (HSCs) require highly regulated rates of protein synthesis, but it is unclear if they or lineage-committed progenitors preferentially recruit transcripts to translating ribosomes. We utilized polysome profiling, RNA sequencing, and whole-proteomic approaches to examine the translatome in LSK (Lin-Sca-1+c-Kit+) and myeloid progenitor (MP; Lin-Sca-1-c-Kit+) cells. Our studies show that LSKs exhibit low global translation but high translational efficiencies (TEs) of mRNAs required for HSC maintenance. In contrast, MPs activate translation in an mTOR-independent manner due, at least in part, to proteasomal degradation of mTOR by the E3 ubiquitin ligase c-Cbl. In the near absence of mTOR, CDK1 activates eIF4E-dependent translation in MPs through phosphorylation of 4E-BP1. Aberrant activation of mTOR expression and signaling in c-Cbl-deficient MPs results in increased mature myeloid lineage output. Overall, our data demonstrate that hematopoietic stem and progenitor cells (HSPCs) undergo translational reprogramming mediated by previously uncharacterized mechanisms of translational regulation.

Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

IncRNAs play an important role in the regulation of gene expression. The present study profiled differentially expressed lncRNAs (DELs) and mRNAs (DEMs) in myelodysplastic syndrome (MDS) to construct a 4­aminobutyrate aminotransferase (ABAT)­DEL­DEM co­expression network in MDS development using the Agilent human BeadChips and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses. Compared with controls, there were 543 DELs and 2,705 DEMs in MDS patients, among which 285 (52.5%) DELs were downregulated and 258 (47.5%) DELs were upregulated, whereas 1,521 (56.2%) DEMs were downregulated and 1,184 (43.70%) DEMs were upregulated in MDS patients. The ABAT­DEL­DEM co­expression network contained six DELs that were co­expressed with ABAT in MDS. The GO analysis revealed that the co­expression network mainly participated in response to organic cyclic compound, cell proliferation, cell part morphogenesis, regulation of cell proliferation and enzyme­linked receptor protein signaling pathways, while the KEGG database showed that the co­expression network was involved in various pathways, such as phagosome and metabolic pathways. Furthermore, the expression of a selected DEL (lncENST00000444102) and ABAT was shown to be significantly downregulated in MDS patients, and in SKM­1 and THP­1 cells. The selected lncENST00000444102 was then overexpressed and ABAT expression was knocked down in the MDS cell lines using lentiviral transfection. In addition, lncENST00000444102 overexpression reduced the viability and increased the apoptosis of MDS cells, ABAT expression was upregulated by lncENST00000444102.

A GC-MS Protocol for Separating Endangered and Non-endangered Pterocarpus Wood Species.

Pterocarpus santalinus and Pterocarpus tincorius are commonly used traded timber species of the genus Pterocarpus. P. santalinus has been listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). As a non-CITES species, P. tincorius is also indiscriminately labeled as P. santalinus due to the similar macroscopic and microscopic features with P. santalinus. In order to understand the molecular discrimination between these easily confused species, xylarium heartwoods of these two species were extracted by three different kinds of solvents and analyzed using gas chromatography⁻mass spectrometry (GC-MS). Multivariate analyses were also applied for the selection of marker compounds that are distinctive between P. santalinus and P. tincorius. A total of twenty volatile compounds were detected and tentatively identified in three kinds of extracts, and these compounds included alcohols, stilbenoids, esters, aromatic hydrocarbons, ketones, miscellaneous, phenols, and flavonoids. GC-MS analyses also revealed that extraction solvents including ethanol and water (EW), ethyl acetate (EA), and benzene⁻ethanol (BE) gave the best chemotaxonomical discrimination in the chemical components and relative contents of the two Pterocarpus species. After chemometric analyses, EW displayed higher predictive accuracy (100%) than those of EA extract (83.33%) and BE extract (83.33%). Furthermore, spathulenol (17.58 min) and pterostilbene (23.65 min) were elucidated as the critical compounds for the separation of the EW extracts of P. santalinus and P. tinctorius. Thus, a protocol of GC-MS and multivariate analyses was developed to use for successfully distinguishing P. santalinus from P. tinctorius.

High methylation of the 4-aminobutyrate aminotransferase gene predicts a poor prognosis in patients with myelodysplastic syndrome.

In our previous study, the 4­aminobutyrate aminotransferase (ABAT) gene was screened and selected as a target gene that may affect the prognosis of myelodysplastic syndrome (MDS). The present study aimed to determine the prognostic value of ABAT in 152 patients with MDS, 29 patients with acute myeloid leukemia (AML) and 40 controls, by detecting the expression and methylation levels of the ABAT gene. In patients with MDS, the expression levels of ABAT were significantly reduced compared with in the controls (P<0.0001), and the degree of DNA methylation was increased in MDS subjects (P<0.0001). Age, hemoglobin level, marrow blasts, International Prognostic Scoring System karyotype, and the expression and methylation levels of ABAT were associated with overall survival (OS), as determined by univariate analysis. Multivariate analysis revealed that older age, higher marrow blasts and higher methylation percentage were independent risk factors for OS. In addition, a functional study demonstrated that ABAT gene silencing increased cell apoptosis and blocked the G1/S phase in SKM­1 and THP­1 human leukemia cells. A γ­aminobutyrate aminotransferase inhibitor also blocked the G1/S phase; however, it had no effect on cell apoptosis. In conclusion, the present study demonstrated that ABAT methylation served an essential role in the progression of MDS and therefore may be considered an indicator of poor prognosis for hematological malignancies.