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.

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.

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.

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.

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.

Effect of combined Bacillomycin D and chitosan on growth of Rhizopus stolonifer and Botrytis cinerea and cherry tomato preservation.

BACKGROUND: Synthetic fungicides are most commonly used for controlling postharvest disease of fruit, although they can cause the emergence of drug-resistant strains, environmental pollution and fruit safety issues. Bacillomycin D (BD), a novel antifungal lipopeptide, and chitosan (CTS) are applied for the preservation of cherry tomato. RESULTS: The combination of BD and CTS showed an additive inhibition on the growth of Rhizopus stolonifer and Botrytis cinerea compared to that of its individual compound. In addition, BD + CTS reduced the incidence of soft rot and gray mold in cherry tomato caused by R. stolonifer and B. cinerea, respectively. Tomato treated with BD + CTS exhibited a lower weight loss and higher firmness and higher contents of total soluble solids, titratable acidity and ascorbic acid compared to those treated with sterile water (control). The kinetics models demonstrated that the shelf life of cherry tomato treated with BD + CTS could be extended by approximately 15 days longer than the control. CONCLUSION: The utilization of BD + CTS provided a novel strategy for reducing postharvest fungal rot and maintaining the storage quality of cherry tomato. © 2020 Society of Chemical Industry.

Phylogenetic signature of lateral exchange of genes for antibiotic production and resistance among bacteria highlights a pattern of global transmission of pathogens between humans and livestock.

The exchange of bacterial virulence factors driven by lateral gene transfer (LGT) can help indicate possible bacterial transmission among different hosts. Specifically, overlaying the phylogenetic signal of LGT among bacteria onto the distribution of respective isolation sources (hosts) can indicate patterns of transmission among these hosts. Here, we apply this approach towards a better understanding of patterns of bacterial transmission between humans and livestock. We utilize comparative genomics to trace patterns of LGT for an 11-gene operon responsible for the production of the antibiotic nisin and infer transmission of bacteria among respective host species. A total of 147 bacterial genomes obtained from NCBI were determined to contain the complete operon. Isolated from human, porcine and bovine hosts, these genomes represented six Streptococcus and one Staphylococcus species. Phylogenetic analyses of the operon sequences revealed a signature of frequent and recent lateral gene transfer that indicated extensive bacterial transmission between humans and pigs. For 11 isolates, we detected a Tn916-like transposon inserted into the operon. The transposon contained the tetM gene (tetracycline resistance) and additional phylogenetic analyses indicated transmission among human and animal hosts. The bacteria possessing the nisin operon and transposon were isolated from hosts distributed globally. These findings possibly reflect both the globalization of the food industry and an increasingly mobile and expanding human population. In addition to concerns regarding zoonosis, these findings also highlight the potential threat to livestock worldwide due to reverse zoonosis.

Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001-2013.

BACKGROUND/AIM: As the knowledgebase of acute myeloid leukemia (AML) has grown, classification systems have moved to incorporate these new findings. METHODS: We assessed 32,941 patients with AML whose records are contained in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Half of all patients diagnosed between 2001 and 2013 did not have a World Health Organization (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with myelofibrosis were associated with the longest leukemia-specific survival (110 and 115 months, respectively), and AML with minimal differentiation and acute megakaryoblastic leukemia with the shortest (30 and 28 months, respectively). For patients in the WHO groups AML not otherwise specified (AML-NOS) and AML with recurrent genetic abnormalities (AML-RGA), the risk of death was greater for older patients and less for married patients. Black patients with any type of AML-NOS also had a higher risk of death. Patients whose case of AML did not receive a WHO classification were older and this group had a higher risk of death when compared to patients with a WHO type of AML-NOS. CONCLUSION: Our findings highlight the divergent outcomes of patients with AML and the importance of using the WHO classification system and demographic factors to gauge their prognosis.

Nano-sized graphene flakes: insights from experimental synthesis and first principles calculations.

In this study, we proposed a cost-effective method for preparing graphene nano-flakes (GNFs) derived from carbon nanotubes (CNTs) via three steps (pressing, homogenization and sonication exfoliation processes). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), laser scattering, as well as ultraviolet-visible and photoluminescence (PL) measurements were carried out. The results indicated that the size of as-synthesized GNFs was approximately 40-50 nm. Furthermore, we also used first principles calculations to understand the transformation from CNTs to GNFs from the viewpoints of the edge formation energies of GNFs in different shapes and sizes. The corresponding photoluminescence measurements of GNFs were carried out in this work.

TBLR1 fuses to retinoid acid receptor α in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia.

The majority of acute promyelocytic leukemia (APL) cases are characterized by the PML-RARα fusion gene. Although the PML-RARα fusion gene can be detected in >98% of APL cases, RARα is also found to be fused with other partner genes, which are also related to all-trans retinoic acid (ATRA)-dependent transcriptional activity and cell differentiation. In this study, we identified a novel RARα fusion gene, TBLR1-RARα (GenBank KF589333), in a rare case of APL with a t(3;17)(q26;q21),t(7;17)(q11.2;q21) complex chromosomal rearrangement. To our knowledge, TBLR1-RARα is the 10th RARα chimeric gene that has been reported up to now. TBLR1-RARα contained the B-F domains of RARα and exhibited a distinct subcellular localization. It could form homodimers and also heterodimers with retinoid X receptor α. As a result, TBLR1-RARα exhibited diminished transcriptional activity by recruitment of more transcriptional corepressors compared with RARα. In the presence of pharmacologic doses of ATRA, TBLR1-RARα could be degraded, and its homodimerization was abrogated. Moreover, when treated with ATRA, TBLR1-RARα could mediate the dissociation and degradation of transcriptional corepressors, consequent transactivation of RARα target genes, and cell differentiation induction in a dose- and time-dependent manner.

Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.

iASPP is a member of the apoptosis-stimulating proteins of p53 (ASPP) family and negatively regulates the apoptotic function of p53. In a hematopoietic system, overexpression of iASPP results in blockage of apoptosis, which may play a role in regulating hematopoietic stem cell (HSC) numbers. To address this, we first analyzed the expression of iASPP in patients with acute leukemia (AL) and found it was highly expressed in patients with AL. We further established a transgenic mouse model in which human iASPP was specifically expressed in hematopoietic cells. Overexpression of iASPP led to an increase in the proportion of long-term HSCs, short-term HSCs, multipotent progenitors, and common myeloid progenitor. HSCs from iASPP transgenic mice had an advantage in long-term reconstitution potential. In addition, the hematopoietic cells from iASPP transgenic mice exhibited a significantly lower level of p53 dependent apoptosis. After irradiation damage, hematopoietic cells of iASPP transgenic mice had a higher level of γ-H2AX expression, which lasted for a longer time. These results provide the first evidence that the iASPP can increase HSC populations and reconstitution capacity. Interestingly, in response to cell damage stimuli, hematopoietic cells can be protected against apoptosis by iASPP; meanwhile these apoptosis-resistant cells would have more mutation accumulation, which might be the potential risk for malignant transformation.-Jia, Y., Peng, L., Rao, Q., Xing, H., Huai, L., Yu, P., Chen, Y., Wang, C., Wang, M., Mi, Y., Wang, J. Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.

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.

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.

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.

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.

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.

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.

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.

Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway.

Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

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.