Pathogenic spectrum and drug resistance of bloodstream infection in patients with acute myeloid leukaemia: a single centre retrospective study.

Background: Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. Methods: From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. Results: A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. Conclusions: In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes.

scRNASequest: an ecosystem of scRNA-seq analysis, visualization, and publishing.

BACKGROUND: Single-cell RNA sequencing is a state-of-the-art technology to understand gene expression in complex tissues. With the growing amount of data being generated, the standardization and automation of data analysis are critical to generating hypotheses and discovering biological insights. RESULTS: Here, we present scRNASequest, a semi-automated single-cell RNA-seq (scRNA-seq) data analysis workflow which allows (1) preprocessing from raw UMI count data, (2) harmonization by one or multiple methods, (3) reference-dataset-based cell type label transfer and embedding projection, (4) multi-sample, multi-condition single-cell level differential gene expression analysis, and (5) seamless integration with cellxgene VIP for visualization and with CellDepot for data hosting and sharing by generating compatible h5ad files. CONCLUSIONS: We developed scRNASequest, an end-to-end pipeline for single-cell RNA-seq data analysis, visualization, and publishing. The source code under MIT open-source license is provided at https://github.com/interactivereport/scRNASequest . We also prepared a bookdown tutorial for the installation and detailed usage of the pipeline: https://interactivereport.github.io/scRNAsequest/tutorial/docs/ . Users have the option to run it on a local computer with a Linux/Unix system including MacOS, or interact with SGE/Slurm schedulers on high-performance computing (HPC) clusters.

Synthesis of poly (L-cysteine)/g-C3N4 modified glassy carbon electrodes for electrochemical detection of methotrexate as a medicine for treatment of breast cancer in pharmaceutical fluid samples.

Analyzing the levels of anticancer medications in biological samples and body fluids reveals important details on the course and effects of chemotherapy. p (L-Cys)/graphitic-carbon nitride (g-C3N4)/GCE, a modified glassy carbon electrode, was created for the current study's electrochemical detection of methotrexate (MTX), a drug used to treat breast cancer, in pharmaceutical fluid samples. l-Cysteine was electro-polymerized on the surface of the g-C3N4/GCE after the g-C3N4 was first modified to prepare the p (L-Cys)/g-C3N4/GCE. Analyses of morphology and structure showed that well-crystalline p (L-Cys) on g-C3N4/GCE was successfully electropolymerized. Studying the electrochemical characteristics of p (L-Cys)/g-C3N4/GCE using CV and DPV techniques revealed a synergistic impact between g-C3N4 and l-cysteine that improved the stability and selectivity of the electrochemical oxidation of MTX while enhancing the electrochemical signal. Results showed that 7.5-780 µM was the linear range, and that 0.11841 µA/µM and 6 nM, respectively, were the sensitivity and limit of detection. The applicability of the suggested sensors was assessed using real pharmaceutical preparations, and the results showed that p (L-Cys)/g-C3N4/GCE had a high degree of precision. Five breast cancer patients who volunteered and provided prepared blood serum samples between the ages of 35 and 50 were used to examine the validity and accuracy of the proposed sensor in the current work for the determination of MTX. The results showed good recovery values (greater than 97.20%), appropriate accuracy (RSD less than 5.11%), and good agreement between the ELISA and DPV analysis results. These findings showed that p (L-Cys)/g-C3N4/GCE can be applied as a trustworthy MTX sensor for MTX level monitoring in blood samples and pharmaceutical samples.

Dysbiosis and primary B-cell immunodeficiencies: current knowledge and future perspective.

According to Elie Metchnikoff, an originator of modern immunology, several pivotal functions for disease and health are provided by indigenous microbiota. Nonetheless, important mechanistic insights have been elucidated more recently, owing to the growing availability of DNA sequencing technology. There are 10 to 100 trillion symbiotic microbes (such as viruses, bacteria, and yeast) in each human gut microbiota. Both locally and systemically, the gut microbiota has been demonstrated to impact immune homeostasis. Primary B-cell immunodeficiencies (PBIDs) are a group of primary immunodeficiency diseases (PIDs) referring to the dysregulated antibody production due to either intrinsic genetic defects or failures in functions of B cells. Recent studies have found that PBIDs cause disruptions in the gut's typical homeostatic systems, resulting in inadequate immune surveillance in the gastrointestinal (GI) tract, which is linked to increased dysbiosis, which is characterized by a disruption in the microbial homeostasis. This study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the crosstalk between the gut microbiome and PBID, the factors shaping the gut microbiota in PBID, as well as the potential clinical approaches for restoring a normal microbial community.

RNASequest: An End-to-End Reproducible RNAseq Data Analysis and Publishing Framework.

We present RNASequest, a customizable RNA sequencing (RNAseq) analysis, app management, and result publishing framework. Its three-in-one RNAseq data analysis ecosystem consists of (1) a reproducible, configurable expression analysis (EA) module, (2) multi-faceted result presentation in R Shiny, a Bookdown document and an online slide deck, and (3) a centralized data management system. In principle, following up our well-received omics data visualization tool Quickomics, RNASequest automates the differential gene expression analysis step, eases statistical model design by built-in covariates testing module, and further provides a web-based tool, ShinyOne, to manage apps powered by Quickomics and reports generated by running the pipeline on multiple projects in one place. Researchers can experience the functionalities by exploring demo data sets hosted at http://shinyone.bxgenomics.com or following the tutorial, https://interactivereport.github.io/RNASequest/tutorial/docs/introduction.html to set up the framework locally to process private RNAseq datasets. The source code released under MIT open-source license is provided at https://github.com/interactivereport/RNASequest.

Emotion recognition with residual network driven by spatial-frequency characteristics of EEG recorded from hearing-impaired adults in response to video clips.

In recent years, emotion recognition based on electroencephalography (EEG) signals has attracted plenty of attention. Most of the existing works focused on normal or depressed people. Due to the lack of hearing ability, it is difficult for hearing-impaired people to express their emotions through language in their social activities. In this work, we collected the EEG signals of hearing-impaired subjects when they were watching six kinds of emotional video clips (happiness, inspiration, neutral, anger, fear, and sadness) for emotion recognition. The biharmonic spline interpolation method was utilized to convert the traditional frequency domain features, Differential Entropy (DE), Power Spectral Density (PSD), and Wavelet Entropy (WE) into the spatial domain. The patch embedding (PE) method was used to segment the feature map into the same patch to obtain the differences in the distribution of emotional information among brain regions. For feature classification, a compact residual network with Depthwise convolution (DC) and Pointwise convolution (PC) is proposed to separate spatial and channel mixing dimensions to better extract information between channels. Dependent subject experiments based on 70% training sets and 30% testing sets were performed. The results showed that the average classification accuracies by PE (DE), PE (PSD), and PE (WE) were 91.75%, 85.53%, and 75.68%, respectively which were improved by 11.77%, 23.54%, and 16.61% compared with DE, PSD, and WE. Moreover, the comparison experiments were carried out on the SEED and DEAP datasets with PE (DE), which achieved average accuracies of 90.04% (positive, neutral, and negative) and 88.75% (high valence and low valence). By exploring the emotional brain regions, we found that the frontal, parietal, and temporal lobes of hearing-impaired people were associated with emotional activity compared to normal people whose main emotional brain area was the frontal lobe.

Spiral wave chimeras in nonlocally coupled bicomponent oscillators.

Chimera states in nonidentical oscillators have received extensive attention in recent years. Previous studies have demonstrated that chimera states can exist in a ring of nonlocally coupled bicomponent oscillators even in the presence of strong parameter heterogeneity. In this study, we investigate spiral wave chimeras in two-dimensional nonlocally coupled bicomponent oscillators where oscillators are randomly divided into two groups, with identical oscillators in the same group. Using phase oscillators and FitzHugh-Nagumo oscillators as examples, we numerically demonstrate that each group of oscillators supports its own spiral wave chimera and two spiral wave chimeras coexist with each other. We find that there exist three heterogeneity regimes: the synchronous regime at weak heterogeneity, the asynchronous regime at strong heterogeneity, and the transition regime in between. In the synchronous regime, spiral wave chimeras supported by different groups are synchronized with each other by sharing a same rotating frequency and a same incoherent core. In the asynchronous regime, the two spiral wave chimeras rotate at different frequencies and their incoherent cores are far away from each other. These phenomena are also observed in a nonrandom distribution of the two group oscillators and the continuum limit of infinitely many phase oscillators. The transition from synchronous to asynchronous spiral wave chimeras depends on the component oscillators. Specifically, it is a discontinuous transition for phase oscillators but a continuous one for FitzHugh-Nagumo oscillators. We also find that, in the asynchronous regime, increasing heterogeneity leads irregularly meandering spiral wave chimeras to rigidly rotating ones.

Mathematical modeling of mechanosensitive reversal control in Myxococcus xanthus.

Adjusting motility patterns according to environmental cues is important for bacterial survival. Myxococcus xanthus, a bacterium moving on surfaces by gliding and twitching mechanisms, modulates the reversal frequency of its front-back polarity in response to mechanical cues like substrate stiffness and cell-cell contact. In this study, we propose that M. xanthus's gliding machinery senses environmental mechanical cues during force generation and modulates cell reversal accordingly. To examine our hypothesis, we expand an existing mathematical model for periodic polarity reversal in M. xanthus, incorporating the experimental data on the intracellular dynamics of the gliding machinery and the interaction between the gliding machinery and a key polarity regulator. The model successfully reproduces the dependence of cell reversal frequency on substrate stiffness observed in M. xanthus gliding. We further propose reversal control networks between the gliding and twitching motility machineries to explain the opposite reversal responses observed in wild type M. xanthus cells that possess both motility mechanisms. These results provide testable predictions for future experimental investigations. In conclusion, our model suggests that the gliding machinery in M. xanthus can function as a mechanosensor, which transduces mechanical cues into a cell reversal signal.

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis.

Objective: Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML. Methods: Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish in vitro models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot. Results: The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells. Conclusion: PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis.

Gastric Cancer Subtypes in Tumour and Nontumour Tissues by Immunologic and Hallmark Gene Sets.

A previous research study on differentiating gastric cancer (GC) into distinct subtypes or prognostic models was mostly based on GC tissues, which neglected the role of nontumour tissues in GC subtypes. The purpose of the research was to identify GC subtypes on the basis of tumour and adjacent nontumour tissues to assess the prognosis of GC patients. We characterized three GC subtypes on the basis of the immunologic and hallmark gene sets in GC and adjacent nontumour tissues: among them, the GC patients with subtype I had the longest survival time compared to patients with other subtypes. The classification was closely associated with T stage and pathological stage of GC patients. A prognostic model containing two gene sets was constructed by LASSO analysis. Kaplan-Meier analysis showed that patients in the high-risk group survived longer than those in the low-risk group and the two prognostic genes sets in the model were strongly correlated with survival status. Then, GO and KEGG analyses and PPI network show that nontumour and tumour tissues are influencing the prognosis of GC patients in separate manners. In summary, we emphasized the prognostic value of nontumour tissue in GC patients and proposed a novel insight that both changes in tumour and nontumour tissues should be taken into account when selecting a treatment strategy for GC.

Therapeutic applications of toll-like receptors (TLRs) agonists in AML.

Acute myeloid leukemia (AML) is an aggressive type of blood cancer affecting bone marrow (BM). In AML, hematopoietic precursors are arrested in the early stages of development and are defined as the presence of ≥ 20% blasts (leukemia cells) in the BM. Toll-like receptors (TLR) are major groups of pattern recognition receptors expressed by almost all innate immune cells that enable them to detect a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns to prime immune responses toward adaptive immunity. Because TLRs are commonly expressed on transformed immune system cells (ranging from blasts to memory cells), they can be a potential option for developing efficient clinical alternatives in hematologic tumors. This is because several in vitro and in vivo investigations have demonstrated that TLR signaling increased the immunogenicity of AML cells, making them more vulnerable to T cell-mediated invasion. This study aimed to review the current knowledge in this field and provide some insight into the therapeutic potentials of TLRs in AML.

The Regulation of Micro-Organisms' Extra-Cellular Polysaccharides on Immunity: A Meta-Analysis.

Extra-cellular polysaccharides (EPSs) have excellent immunomodulatory functions. In order to further promote their application, we studied the ability of extra-cellular polysaccharides from different sources to regulate immunity. We studied the association of extra-cellular polysaccharides with immune factors (Interleukin (IL-2, IL-4, IL-10), Interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), Immunoglobulin A (IgA), and Immunoglobulin G (IgG)) and different concentrations of EPSs and interfering media on experimental results by using a forest plot under fixed-effect or random-effects models. Through Google, PubMed, Embase, ScienceDirect, and Medline, from 2000 to 2021, 12 articles were included. We found that exopolysaccharides (from bacteria or fungi) could significantly increase the immune index of spleen and thymus, spleen index (SMD: 2.11, '95%CI: [1.15, 3.08]'; p < 0.01), and thymus index (SMD: 1.62, '95%CI: [0.93, 2.32]'; p = 0.01 < 0.05). In addition, exopolysaccharides had a significant effect on TNF-α (SMD: 0.94, '95%CI: [0.29, 1.59]'; p = 0.01 < 0.05). For IL-4 (SMD: 0.49, '95%CI: [0.01, 0.98]'; p = 0.046 < 0.05), extra-cellular polysaccharides had a statistically significant effect on immunity. Although the data of other immune factors were not ideal, the comprehensive analysis showed that exopolysaccharides also had an effect on the release of these five immune factors. In the sub-group analysis, different concentrations of EPSs affected the results of experiments on the spleen and thymus, and the CY intervention had a relatively significant effect on immune regulation. Taken together, our study highlighted that EPSs have a significant impact on immune regulation.

Rh-Catalyzed Highly Enantioselective Hydrogenation of Functionalized Olefins with Chiral Ferrocenylphosphine-Spiro Phosphonamidite Ligands.

A highly efficient Rh-catalyzed hydrogenation of functionalized olefins has been realized by a new family of highly rigid chiral ferrocenylphosphine-spiro phosphonamidite ligands. Excellent enantiocontrol (>99% ee in most cases) was achieved with a wide range of α-dehydroamino acid esters and α-enamides. This practicable catalytic system was further applied in the scalable synthesis of highly optically pure key intermediates of cinacalcet and d-phenylalanine.

Arsenic trioxide induces proteasome dependent TBLR1-RARα degradation to improve leukemia eradication through cell differentiation enhancement.

BACKGROUND: Acute promyelocytic leukemia (APL) mainly harbors PML-RARα fusion gene, which is sensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) treatment. However, APL harboring other RARα fusion genes exhibit different drug sensitivity. Here, we investigated the role and mechanism of TBLR1-RARα, a rare RARα fusion gene, on ATO treatment in leukemia cells. METHODS: By constructing two cell models of leukemia cell line HL-60 and U937 with overexpressed TBLR1-RARα, we detected the cell differentiation in the two cell models after ATO treatment by flow cytometry and Wright staining. Meanwhile, cell viability, colony formation and apoptosis were also determined after ATO treatment. RESULTS: We found that TBLR1-RARα enhanced ATO-induced apoptosis and cell proliferation inhibition. Besides, TBLR1-RARα also promoted ATO-induced cell differentiation. Furthermore, we found that the mitochondrial caspase pathway was involved in the apoptosis induced by ATO treatment in TBLR1-RARα positive leukemia cells. Moreover, ATO mediated TBLR1-RARα protein degradation via proteasome pathway, which accounts for the transcriptional activation of RARα target gene and is further involved in cell differentiation of TBLR1-RARα positive leukemia cells. CONCLUSIONS: Our study provides evidence that TBLR1-RARα positive APL patients may benefit from ATO treatment, thereby improving the appropriate management in TBLR1-RARα positive APL.

Tetramethyl bisphenol a inhibits leydig cell function in late puberty by inducing ferroptosis.

Tetramethyl bisphenol A (TMBPA) is a commonly used bisphenol analog, used as a fire retardant. However, whether it inhibits the function of Leydig cells in late puberty remains unclear. In this study, 35-day-old male Sprague-Dawley rats were gavaged with 0, 10, 100, and 200 mg/kg body weight TMBPA for 21 days. TMBPA significantly reduced serum testosterone levels at 10 mg/kg and higher doses without altering serum luteinizing hormone and follicle-stimulating hormone levels. TMBPA significantly increased serum iron concentraion while reducing the ratio of serum glutathione (GSH) and GSH/GSSG (oxidized glutathione disulfide). In addition, TMBPA significantly increased testicular iron amount at 10 mg/kg and higher doses and malondialdehyde level at 200 mg/kg. TMBPA down-regulated the expression of Leydig cell genes, including Nr5a1, Star, Scarb1, Insl3, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd11b1, and their proteins. In addition, TMBPA markedly down-regulated the expression of genes in the ferroptosis pathway (Tp53, Slc7a11, Sod1, Sod2, Cat, Sqstm1, Keap1, and Hmox1). TMBPA significantly reduced the levels of ferroptosis pathway proteins (TP53, SLC7A11, GPX4, SQSTM1, KEAP1, NRF2, and HMOX1) in Leydig cells in vivo. Immature and adult Leydig cell culture in vitro also showed that TMBPA significantly reduced testosterone concentrations in the medium, which can be reversed by a ferroptosis inhibitor. After 24 h of culture in primary Leydig cells at 10 and 50 µM, TMBPA significantly induced reactive oxygen species and lowered the mitochondrial membrane potential. TMBPA also altered protein levels in the ferroptosis pathway in Leydig cells in vitro. In conclusion, TMBPA directly inhibits the activity of rat Leydig cell steroidogenic enzymes and induces the ferroptosis of Leydig cells, thereby inhibiting the testosterone synthesis of Leydig cells in the late puberty.

CellDepot: A Unified Repository for scRNA-seq Data and Visual Exploration.

CellDepot containing over 270 datasets from 8 species and many tissues serves as an integrated web application to empower scientists in exploring single-cell RNA-seq (scRNA-seq) datasets and comparing the datasets among various studies through a user-friendly interface with advanced visualization and analytical capabilities. To begin with, it provides an efficient data management system that users can upload single cell datasets and query the database by multiple attributes such as species and cell types. In addition, the graphical multi-logic, multi-condition query builder and convenient filtering tool backed by MySQL database system, allows users to quickly find the datasets of interest and compare the expression of gene(s) across these. Moreover, by embedding the cellxgene VIP tool, CellDepot enables fast exploration of individual dataset in the manner of interactivity and scalability to gain more refined insights such as cell composition, gene expression profiles, and differentially expressed genes among cell types by leveraging more than 20 frequently applied plotting functions and high-level analysis methods in single cell research. In summary, the web portal available at http://celldepot.bxgenomics.com, prompts large scale single cell data sharing, facilitates meta-analysis and visualization, and encourages scientists to contribute to the single-cell community in a tractable and collaborative way. Finally, CellDepot is released as open-source software under MIT license to motivate crowd contribution, broad adoption, and local deployment for private datasets.

Effect of slurry ice during storage on myofibrillar protein of Pseudosciaena crocea.

In order to explore the effect of slurry ice on myofibrillar protein of Pseudosciaena crocea, the changes in myofibrillar protein and muscle microstructure during storage were studied with crushed ice as a control. During the storage period, the rate of decrease in myofibrillar protein content, Ca2+-ATPase activity, and total sulfhydryl groups in the slurry ice group was lower than in the control group (p < .05). There was a significant linear correlation between the hydrophobicity and the storage time (R crushed ice (4℃) = 0.9881, R slurry ice (4℃) = 0.9878, R slurry ice (-1℃) = 0.9674), and trichloroacetic acid (TCA) soluble peptide content was lower than in the control group at the same time. Slurry ice (-1℃) was optimal in maintaining protein content in P. crocea; the arrangement of myofibrils in P. crocea treated by slurry ice was compact and the gaps were small. Slurry ice can delay the denaturation and degradation of fish myofibrillar protein and maintain its quality.

A novel fusion protein TBLR1-RARα acts as an oncogene to induce murine promyelocytic leukemia: identification and treatment strategies.

Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARα and its fusion partners. For decades, the advent of all-trans retinoic acid (ATRA) synergized with arsenic trioxide (As2O3) has turned most APL from highly fatal to highly curable. TBLR1-RARα (TR) is the tenth fusion gene of APL identified in our previous study, with its oncogenic role in the pathogenesis of APL not wholly unraveled. In this study, we found the expression of TR in mouse hematopoietic progenitors induces blockade of differentiation with enhanced proliferative capacity in vitro. A novel murine transplantable leukemia model was then established by expressing TR fusion gene in lineage-negative bone marrow mononuclear cells. Characteristics of primary TR mice revealed a rapid onset of aggressive leukemia with bleeding diathesis, which recapitulates human APL more accurately than other models. Despite the in vitro sensitivity to ATRA-induced cell differentiation, neither ATRA monotherapy nor combination with As2O3 confers survival benefit to TR mice, consistent with poor clinical outcome of APL patients with TR fusion gene. Based on histone deacetylation phenotypes implied by bioinformatic analysis, HDAC inhibitors demonstrated significant survival superiority in the survival of TR mice, yielding insights into clinical efficacy against rare types of APL.

New developments in anti-biofilm intervention towards effective management of orthopedic device related infections (ODRI's).

Orthopedic device related infections (ODRI's) represent a difficult to treat situation owing to their biofilm based nature. Biofilm infections once established are difficult to eradicate even with an aggressive treatment regimen due to their recalcitrance towards antibiotics and immune attack. The involvement of antibiotic resistant pathogens as the etiological agent further worsens the overall clinical picture, pressing on the need to look into alternative treatment strategies. The present review highlightes the microbiological challenges associated with treatment of ODRI's due to biofilm formation on the implant surface. Further, it details the newer anti-infective modalities that work either by preventing biofilm formation and/or through effective disruption of the mature biofilms formed on the medical implant. The study, therefore aims to provide a comprehensive insight into the newer anti-biofilm interventions (non-antibiotic approaches) and a better understanding of their mechanism of action essential for improved management of orthopedic implant infections.

Hollow porous BiOCl microspheres assembled with single layer of nanocrystals: spray solution combustion synthesis and the enhanced photocatalytic properties.

The hollow porous microspheres assembled with BiOCl nanocrystals were successfully synthesized via a facile spray solution combustion synthesis method. The microstructure, morphology, absorbance, optical properties of the samples were investigated in detail. The results show that hollow porous BiOCl microspheres have narrow band gaps (2.66-2.71 eV), and the degradation rate of rhodamine B (RhB) can reach 98% under visible light irradiation for 60 min. Furthermore, the mechanism of the photocatalytic degradation of RhB was proposed through the experiment of trapping active species. This excellent photocatalytic property can be ascribed to the larger specific surface area and the special microstructure.