SRplot: A free online platform for data visualization and graphing.

Graphics are widely used to provide summarization of complex data in scientific publications. Although there are many tools available for drawing graphics, their use is limited by programming skills, costs, and platform specificities. Here, we presented a freely accessible easy-to-use web server named SRplot that integrated more than a hundred of commonly used data visualization and graphing functions together. It can be run easily using all Web browsers and there are no strong requirements on the computing power of users' machines. With a user-friendly graphical interface, users can simply paste the contents of the input file into the text box according to the defined file format. Modification operations can be easily performed, and graphs can be generated in real-time. The resulting graphs can be easily downloaded in bitmap (PNG or TIFF) or vector (PDF or SVG) format in publication quality. The website is updated promptly and continuously. Functions in SRplot have been improved, optimized and updated depend on feedback and suggestions from users. The graphs prepared with SRplot have been featured in more than five hundred peer-reviewed publications. The SRplot web server is now freely available at http://www.bioinformatics.com.cn/SRplot.

LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia.

Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1 is found to contribute to carcinogenesis, but its role in acute promyelocytic leukemia (APL) is unclear. In this study, by analyzing data from Gene Expression Omnibus, The Cancer Genome Atlas database and our clinical samples, we found that KCNQ1OT1 was selectively highly expressed in APL. Functional assays demonstrated that knockdown of KCNQ1OT1 reduced APL cell proliferation and increased apoptosis. Further evidence showed that KCNQ1OT1 was mainly located in the cytoplasm of APL patient-derived NB4 cells and APL patient bone marrow samples. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA. Whereas KCNQ1OT1 and FUS did not affect each other. Importantly, knockdown of MAP3K1 impaired APL cell proliferation. Finally, c-Myc transactivated KCNQ1OT1 in APL cells through binding to its promoter while knockdown of c-Myc decreased KCNQ1OT1 expression. Our results not only revealed that c-Myc transactivated KCNQ1OT1 and upregulated KCNQ1OT1 promoted APL cell proliferation, but also demonstrated that KCNQ1OT1 bound to FUS to synergistically stabilize MAP3K1 mRNA, thus facilitating APL cell proliferation. This study established a previously unidentified role of KCNQ1OT1 in the development of APL, and KCNQ1OT1 may serve as a potential therapeutic target for APL.

Acute leukemia in pregnancy: a single institutional experience with 21 cases at 10 years and a review of the literature.

INTRODUCTION: Acute leukemia (AL) occurring in pregnancy is extremely rare, and its treatment is a clinical dilemma. METHODS: We retrospectively reviewed the medical records of our hospital from 2010 to 2019. RESULTS: Twenty-one patients were diagnosed with AL during pregnancy. Of whom, eighteen had acute myeloid leukemia, and 3 had acute lymphoblastic leukemia. Six, eight and seven patients were diagnosed during the first, second, and third trimester, respectively. Six of the 21 patients experienced therapeutic abortion and 1 had spontaneous abortion, whereas 9 gave birth to healthy babies (4 through vaginal deliveries and 5 with Caesarean sections). Four babies had been exposed to chemotherapeutic agents, but no congenital malformations were observed. Sixteen patients received chemotherapy, while 4 patients died before chemotherapy and one was discharged after refusing chemotherapy. The complete remission rate of the 10 patients who began chemotherapy immediately after diagnosis was 80%, compared with 66.7% in the 6 patients who started chemotherapy after abortion or delivery. Three remain alive. CONCLUSIONS: In general, initiation of chemotherapy as early as possible may increase the CR rate. Combined with literature data, we proposed that, for patients diagnosed in early and late stages of pregnancy (>30 weeks), elective termination or induced delivery before chemotherapy may be a good choice for better maternal (and fetal) outcome.KEY MESSAGESAcute leukaemia diagnosed in pregnancy is extremely rare, and its treatment is a clinical dilemma.In general, initiation of chemotherapy as early as possible may increase the CR rate.For patients who are diagnosed in the first trimester or late stage of pregnancy (>30 weeks), elective termination or induced delivery before starting chemotherapy may be a good choice for better maternal (and fetal) outcome.

C/EBPα is indispensable for PML/RARα-mediated suppression of long non-coding RNA NEAT1 in acute promyelocytic leukemia cells.

Better understanding of the transcriptional regulatory network in acute promyelocytic leukemia (APL) cells is critical to illustrate the pathogenesis of other types of acute myeloid leukemia. Previous studies have primarily focused on the retinoic acid signaling pathway and how it is interfered with by promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) fusion protein. However, this hardly explains how APL cells are blocked at the promyelocytic stage. Here, we demonstrated that C/EBPα bound and transactivated the promoter of long non-coding RNA NEAT1, an essential element for terminal differentiation of APL cells, through C/EBP binding sites. More importantly, PML/RARα repressed C/EBPα-mediated transactivation of NEAT1 through binding to NEAT1 promoter. Consistently, mutation of the C/EBP sites or deletion of retinoic acid responsive elements (RAREs) and RARE half motifs abrogated the PML/RARα-mediated repression. Moreover, silencing of C/EBPα attenuated ATRA-induced NEAT1 upregulation and APL cell differentiation. Finally, simultaneous knockdown of C/EBPα and C/EBPß reduces ATRA-induced upregulation of C/EBPε and dramatically impaired NEAT1 activation and APL cell differentiation. In sum, C/EBPα binds and transactivates NEAT1 whereas PML/RARα represses this process. This study describes an essential role for C/EBPα in PML/RARα-mediated repression of NEAT1 and suggests that PML/RARα could contribute to the pathogenesis of APL through suppressing C/EBPα targets.

Recent progress in study of circRNAs and its role in leukemia.

Circular RNAs (circRNAs) are a class of newly identified noncoding RNA and are considered as a new feature of eukaryotic gene expression. Hundreds of thousands of endogenous circRNAs have been found in mammalian cells, which we knew little before. CircRNAs are covalently closed, circular RNA molecules that typically comprise exonic sequences and are spliced at canonical splice sites. Researchers with RNA-Seq technology have identified that the expression of circRNAs is developmentally regulated, tissue- and cell-type specific. Like long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the RNA field, and aberrant expression of circRNAs could contribute to carcinogenesis. Recent studies have demonstrated that circRNAs play important roles in the development, maintenance, and progression of leukemia. Herein, we describe the biologic characteristics and functions of circRNAs, with a focus on circRNAs that play essential roles in leukemia.

Effect of amendments on soil Cd sorption and trophic transfer of Cd and mineral nutrition along the food chain.

Phytotoxicity of cadmium (Cd) and its trophic transfer along a terrestrial food chain have been extensively investigated. However, few studies focused on the role of amendments on the trophic transfer of Cd and related mineral nutrients. In a 60-day pot experiment, soil Cd availability, accumulation of Cd, mineral nutrients (Ca and Si) in lettuce, and subsequent trophic transfer along the lettuce-snail system were investigated with or without 3% (w/w) soil amendment (biochar or micro-hydroxyapatite, µHAP). Soil CaCl2 extractable Cd (CdCaCl2) contents decreased by both amendments. µHAP amended soil increased the Freundlich sorption capacity of Cd2+ to a greater extent (15.9 mmol/kg) than biochar (12.6 mmol/kg). Cd, Ca and Si accumulation in lettuce tissues (roots and shoots) varied with amendment species and soil Cd levels. Linear regression analysis showed that root Cd contents are negatively correlated with root Ca and Si contents (r2 = 0.96, p < 0.05). But no significant correlation between shoot Cd and lettuce Ca and Si contents was found (p > 0.05). After 15 days snail feeding, nearly 90% content of Cd was found in snail viscera, while nearly 95% content of Ca was found in snail shells. Contents of Si distributed equally in snail tissues. Biomagnification of Cd, Ca and Si (TF > 1) was found in lettuce shoot - snail viscera system. Opposite tendency of TF variation between Cd and nutrient elements (Ca and Si) from shoots to snail tissues indicated that µHAP, rather than biochar, amendment is applicable to remediate soil Cd contamination in our study.

Effects of soil amendments on cadmium transfer along the lettuce-snail food chain: Influence of chemical speciation.

Cadmium (Cd) trophic transfer along the soil-lettuce-snail food chain was investigated using the root bags-based pot experiments. Two amendments (corn straw biochar and micro-hydroxyapatite (µHAP)) were investigated on Cd (0, 2.5, and 5 mg/kg soil) availability in soils, chemical distribution in plant cells and accumulation in snails. After 60 days, both the CaCl2 extractable Cd in rhizosphere soil (CdCaCl2,rhizo) and Cd accumulation in lettuce decreased with amendments addition. Biochar had a great capacity to reduce both Cd contents and toxicity-sensitive associated Cd (CdFi+Fii) percentages in lettuce roots at 2.5 mg/kg Cd contaminated soil; while µHAP generates a higher reduction in both Cd contents and chain transfer associated Cd (CdFi+Fii+Fiii) percentages in lettuce shoots at 5 mg/kg Cd contaminated soil. Linear regression showed that both contents of root CdFi+Fii and shoot CdFi+Fii+Fiii are better correlated with the CdCaCl2,rhizo (R2 > 0.70, p < 0.01). After 15 days feeding, almost 90% content of Cd accumulated in snail viscera. µHAP had a higher reduction in snail soft tissues Cd accumulation than biochar. Distributions of Cd in snail tissues are significantly correlated with CdFi+Fii+Fiii in shoots (viscera R2 = 0.835; soft tissue R2 = 0.771). Established quantitative relationships could be used to predict the bioavailability and transfer of Cd in terrestrial food chain in the presence of amendments.

Distribution and Phytoavailability of Potentially Toxic Metals in Different Fe/Mg Mine Tailings.

The environmental risk of potentially toxic metals in tailing soils is of universal concern. We conducted a 3-month pot experiment to research the distribution and variations of potentially toxic metals (PTMs), and the translocation and accumulation capability of these metals (Cr, Ni, Mn, Cu, Zu) in natural plants for three Fe/Mg tailing soils (serpentine-type, olivine-type and magnetite-type) with growth of a grass plant-Imperata cylindrica. We used comparative analysis, regression analysis and correlation analysis to process relevant experimental data. Results showed the rhizosphere tailing soils decreased from 3.70% to 16.8%, compared to the bulk soils, after growth of Imperata cylindrica, and the acid soluble fraction of Mn, Cu and Zn increased significantly. Cu and Zn were more bioavailable than other PTMs, especially for serpentine-type tailing soils. Linear regression analysis indicated that non-residual fractions showed different effects on metal concentrations of Imperata cylindrica. The non-residual metal fractions of serpentine-type and olivine-type tailing soils showed better correlations with metal concentrations in grass plants than those of magnetite-type tailing soils. We found that the chemical compositions of tailing soils showed remarkable effects on Ni and Mn compared with other elements, especially Mg and Al. Overall, the grass plant can alter the metal distribution, enhance metal bioavailability and promote land use of Fe/Mg tailing soils.

[Spatial Distributions of Transferable Nitrogen Forms and Influencing Factors in Sediments from Inflow Rivers in Different Lake Basins].

It is necessary to investigate the distribution of nitrogen forms in river sediments to recognize the water environment quality. In this study, ion exchangeable form nitrogen(IEF-N), weak acid extractable form nitrogen (WAEF-N), strong alkali extractable form nitrogen (SAEF-N) and strong oxidation extractable form nitrogen (SOEF-N) in sediments were obtained by means of sequential extraction procedures.We analyzed the spatial variations of nitrogen forms in sediments from Taihu watershed (Dongtiaoxi River and Xitiaoxi River) and Hongzehu watershed (Anhe River and Suihe River), and expounded the influence factors of nitrogen form distribution. The results showed that the physicochemical properties of sediments from different watersheds varied in space. The concentrations of total nitrogen and nitrogen fractions also showed obvious changes in river sediments. As a whole, the concentrations of total nitrogen and transferable nitrogen in Taihu rivers were higher than those in Hongzehu rivers, but the former showed smaller spatial changes. Sediments from Taihu rivers showed the different concentration order of total nitrogen and transferable nitrogen comparing with those from Hongzehu rivers. The former followed the order of SOEF-N > SAEF-N > IEF-N > WAEF-N, and the latter followed the order of SOEF-N > SAEF-N > WAEF-N > IEF-N.The spatial varitions of transferable nitrogen fractions in Hongzehu rivers were prominent, which was associated with nitrogen sources. The spatial distributions of transferable nitrogen in sediments were obviously affected by their physicochemical properties, especially for organic matter and grain size.

Targeting the RhoA-ROCK pathway to regulate T-cell homeostasis in hypoxia-induced pulmonary arterial hypertension.

BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a crippling disease with limited therapeutic methods. The imbalance of T helper 17 cell (Th17)/regulatory T cell (Treg) plays an important role in the development of Hypoxic PAH. However, whether targeting the ras homolog family member A-Rho kinase (RhoA-ROCK) pathway (activation and inhibition) by lysophosphatidic acid (LPA) and fasudil (FSD) regulate T-cell homeostasis in Hypoxic PAH remain unknown. OBJECTIVE: To examine the effects of LPA and FSD on hypoxic pulmonary vascular remodeling and homeostasis of Th17/Treg cells in Hypoxic PAH. METHODS: Rats were exposed to hypoxia (10 ±â€¯0.5% O2) to induce Hypoxic PAH. The experiments consists of two parts. Forty rats were randomly divided into four groups (n = 10): normoxia group, normoxia + LPA group, hypoxia group and hypoxia + LPA group. Thirty rats were randomly divided into another three groups (n = 10): normoxia group, hypoxia group, and hypoxia + FSD group. Rats in normoxia + LPA group and hypoxia + LPA group were intraperitoneally injected 40 µg/kg LPA daily. Rats in hypoxia + FSD group were intraperitoneally injected 30 mg/kg fasudil daily. The effects of LPA and FSD on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, and on changes of Th17/Treg cells and levels of interleukin-17 (IL-17) and IL-10 were examined. RESULTS: PAH and RV hypertrophy occurred in rats exposed to hypoxia. LPA exacerbated hypoxic pulmonary vascular remodeling and FSD inhibited it. LPA increased Th17/Treg imbalance in peripheral blood and spleen. However, after treatment with FSD, hypoxic PAH rats showed an obvious reduction of Th17 cells as well as an increase of Treg cells. LPA increased the expression of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) and reduced the p-STAT5 in peripheral blood and spleen in hypoxic PAH rats. The expression of p-STAT3 and p-STAT5 in hypoxic PAH rats treated with FSD showed opposite changes. LPA increased the expression of IL-17 and reduced the IL-10 in small intrapulmonary arteries and serum in hypoxic PAH. However, the expression of IL-17 and IL-10 in hypoxic PAH rats treated with FSD showed opposite changes. CONCLUSIONS: Activation and inhibition of RhoA-ROCK pathway by LPA and FSD modulated the homeostasis of Th17/Treg cells via regulating STAT3/STAT5 phosphorylation in hypoxic PAH. Thus, Apart from influence of pulmonary vascular remodeling, regulation of Th17/Treg homeostasis by RhoA-ROCK pathway play a key role in hypoxic PAH.

C/EBPß contributes to transcriptional activation of long non-coding RNA NEAT1 during APL cell differentiation.

Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPß bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPß binding sites both around -54 bp and -1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPß was increased after ATRA treatment, and the binding of C/EBPß in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPß significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPß directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPß impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPß contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPß in APL cell differentiation.

[Investigation and analysis for current situation and pathogenesis relevant to pulmonary hypertension].

OBJECTIVE: To investigate the demographic characteristics and the causes for pulmonary hypertension (PH) in adult patients.
 Methods: A total of 2 508 adult patients diagnosed as PH, who came from the Second Xiangya Hospital of Central South University from January 2010 to December 2014, were retrospectively investigated. All subjects underwent the clinical diagnosis, or the echocardiographic diagnosis, or thetraditional hemodynamic criteria by right heart catheterization (RHC). The patient's data including hospital numbers, gender, ages, primary diseases, etc, are collected and analyzed.
 Results: In this study, the number of patients diagnosed as PH was increased year by year. The median age of 2 508 patients was 47 (18-93) years old, and there were 933 males (37.2%), the ratio of male to female was 1:1.69 (P<0.05). Female was more common in Class I PH (pulmonary arterial hypertension) and Class II PH (pulmonary hypertension due to left heart disease)(>70%), but there were more male patients (74.5%) in Class III PH (pulmonary hypertension due to lung diseases and/or hypoxia). In our study, 896 cases (35.73%) were the Class I PH, 1 163 cases was the Class II PH (46.37%), 411 cases was the Class III PH (16.39%), and the Class IV PH (chronic thromboembolic pulmonary hypertension) and the Class V PH (PH with unclear and/or multifactorial mechanisms) were diagnosed in 32(1.27%) and 6 patients (0.24%), respectively.The diseases with largest number of patients for the top 7 primary PH were rheumatic heart disease (1 090, 43.48%), congenital heart disease (692, 27.60%), chronic obstructive pulmonary disease (358, 14.28%), connective tissue related disease(156, 6.22%), valvular heart disease (66, 2.63%), idiopathic PH (46, 1.83%) and pulmonary embolism (27, 1.08%).
 Conclusion: Adult PH patients' peak incidence age is 41-50 years old. This disease is more common among women, and the Class I/II PH are common in women while the Class III is more common in men. Rheumatic heart disease and congenital heart disease may be the most common cause for pulmonary hypertension in China, and chronic obstructive pulmonary disease is the most common cause for the Class III PH, in which the patients are old.

Risk assessment using the species sensitivity distribution method: data quality versus data quantity.

Species sensitivity distributions (SSDs) are cumulative distributions of measures of species sensitivity to a stressor or toxicant, and are used to estimate concentrations that will protect p% of a community (PCp ). There is conflict between the desire to use high-quality sensitivity data in SSDs, and to construct them with a large number of species forming a representative sample. Trade-offs between data quality and quantity were investigated using the effects of increasing salinity on the macroinvertebrate community from the Hunter River catchment, in eastern Australia. Five SSDs were constructed, representing five points along a continuum of data quality versus data quantity and representativeness. This continuum was achieved by the various inclusion/exclusion of censored data, nonmodeled data, and extrapolation from related species. Protective concentrations were estimated using the Burr type III distribution, Kaplan-Meier survival function, and two Bayesian statistical models. The dominant taxonomic group was the prime determinant of protective concentrations, with an increase in PC95 values resulting from a decrease in the proportion of Ephemeropteran species included in the SSD. In addition, decreases in data quantity in a SSD decreased community representativeness. The authors suggest, at least for salinity, that the inclusion of right censored data provides a more representative sample of species that reflects the natural biotic assemblage of an area to be protected, and will therefore improve risk assessment.