APAview: A Web-Based Platform for Alternative Polyadenylation Analyses in Hematological Cancers

Background: Hematologic malignancies, such as acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), are cancers that start in blood-forming tissues and can affect the blood, bone marrow, and lymph nodes. They are often caused by genetic and molecular alterations such as mutations and gene expression changes. Alternative polyadenylation (APA) is a post-transcriptional process that regulates gene expression, and dysregulation of APA contributes to hematological malignancies. RNA-sequencing-based bioinformatic methods can identify APA sites and quantify APA usages as molecular indexes to study APA roles in disease development, diagnosis, and treatment. Unfortunately, APA data pre-processing, analysis, and visualization are time-consuming, inconsistent, and laborious. A comprehensive, user-friendly tool will greatly simplify processes for APA feature screening and mining. Results: Here, we present APAview, a web-based platform to explore APA features in hematological cancers and perform APA statistical analysis. APAview server runs on Python3 with a Flask framework and a Jinja2 templating engine. For visualization, APAview client is built on Bootstrap and Plotly. Multimodal data, such as APA quantified by QAPA/DaPars, gene expression data, and clinical information, can be uploaded to APAview and analyzed interactively. Correlation, survival, and differential analyses among user-defined groups can be performed via the web interface. Using APAview, we explored APA features in two hematological cancers, APL and AML. APAview can also be applied to other diseases by uploading different experimental data

Unveiling the molecular landscape of δ-thalassemia and δ-globin variants in southern China: novel mutations, gene spectrum, and implications for thalassemia diagnosis

Objectivesδ-thalassemia and δ-globin variants are rare hemoglobinopathies. However, co-inheritance of β-thalassemia and δ-globin gene mutations may affect the diagnosis of β-thalassemia carriers when based on the elevated Hb A2. This study aimed to identify and characterize δ-thalassemia and δ-globin variants in Southern China.MethodsNinety samples with suspected δ-globin gene mutations from 15,642 participants were selected for further molecular analysis based on their Hb A2 level (≦1.8%) and hematological parameters. Additionally, 37 samples with suspected δ-globin gene mutations were sent from other hospital to our laboratory for identification. GAP-PCR and PCR-reverse dot blot (PCR-RDB) were used to detect common α- and β-thalassemia in the Chinese population, and Sanger sequencing was used to identify δ-globin gene mutations.ResultsAmong 15,642 samples examined, samples with δ-globin gene mutations were identified in 127 (0.81%) cases with as many as 28 different genotypes, including 81 (0.52%) cases of δ-thalassemia and 46 (0.29%) cases of δ-globin variants. The most prevalent δ-thalassemia and δ-globin variants of this study were HBD:c.−127T>C (75.3%, 61/81) and Hb A2-Melbourne (54.3%, 25/46). Most of the samples were heterozygous (87.4%, 111/127), and only two cases of homozygous were detected. There were three double heterozygotes and 11 cases of combined α/β-globin mutations. Notably, we also identified eight cases of novel mutations in the δ-globin gene. In both heterozygous and homozygous cases, δ-globin mutations maintained hematological parameters within normal ranges, while their co-occurrence with α- or β-thalassemia manifested as a thalassemia phenotype characterized by significantly reduced MCV and MCH values.ConclusionThe study reveals that δ-globin gene mutations are prevalence in the South China and necessitates integration of δ-globin screening into existing thalassemia prevention protocols

Rising Powers and Order Contestation: Disaggregating the Normative from the Representational

One of the central themes of the current literature on rising powers is that new aspirants to great power status pose a challenge to the underlying principles and norms that underpin the existing, Western-led order. However, in much of the literature, the nature and significance of rising powers for international order is imprecisely debated, in particular the concept and practice of ‘contestation’. In this article we aim to establish a distinction between normative contestation and what can be thought of as ‘contestation over representation’: that is, contestation over who is setting and overseeing the rules of the game rather than the content of the rules themselves and the kind of order that they underpin. This distinction is important for providing a more nuanced understanding of the nature of the current power transition and therefore for guiding attempts at accommodation on the part of the established powers. Theoretically, the paper engages with debates on international order and international society. Its empirical basis is provided by a thorough analysis of the discourse of rising power summitry, in particular at meetings of the BRICS and Shanghai Cooperation Organization groupings

Antiviral activity of nitazoxanide against pseudorabies virus infection in vitro

Pseudorabies (PR), an infectious disease caused by pseudorabies virus (PRV), has been responsible for substantial economic losses within the global swine industry. However, effective control measures and vaccines against PRV remain limited, thereby underscoring the necessity for the development of innovative antiviral agents targeting PRV. Nitazoxanide (NTZ) is an FDA-approved anthelminthic drug, has shown efficacy in inhibiting a variety of viral infections. This study aims to evaluate the antiviral properties of NTZ against PRV infection in vitro. The findings demonstrated that NTZ treatment significantly inhibited PRV infection in a dose-dependent manner in both PK15 and Vero cell lines, with the primary inhibitory effect occurring during the viral replication phase, rather than during the attachment, entry, or release phases of the virus. Subsequent RNA-Seq analysis revealed that cellular signaling pathways related to oxidative stress were implicated in the antiviral efficacy of NTZ against PRV infection. In conclusion, our findings implicate that NTZ effectively suppress PRV infection in vitro, suggesting its potential as a promising antiviral candidate for the clinical interventions in Alphaherpesvirinae infections

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