Clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma

Objective·To analyze the clinical characteristics and prognostic risk factors of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the prognostic effects of autologous stem cell transplantation (ASCT) and rituximab maintenance therapy on DLBCL patients.Methods·The clinical data of 160 patients with DLBCL who were first diagnosed by pathology and immunotyping were collected from the Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020, and the risk factors affecting the efficacy and prognosis of patients were analyzed. Moreover, the clinical characteristics of patients with relapsed/refractory DLBCL and the effect of salvage ASCT on overall survival (OS) were assessed. For those high-risk patients who achieved complete remission (CR) in the interim assessment, the impact of ASCT and rituximab maintenance therapy on survival outcomes was further assessed.Results·Patients with initial age of treatment >60 years (P=0.005), International Prognostic Index (IPI) 3‒5 scores (P=0.032), low albumin level (P=0.001) and anemia (P=0.007) had poor efficacy. Multivariate analysis showed that the initial age of treatment >60 years (HR=2.788, 95%CI 1.575‒4.936, P=0.000), non-GCB subtype (HR=2.230, 95%CI 1.150‒4.324, P=0.018), elevated lactate dehydrogenase level (HR=2.064, 95%CI 1.006‒4.234, P=0.048) and low albumin level (HR=2.052, 95% CI 1.169‒3.602, P=0.012) were the independent risk factors for progression-free survival (PFS). The initial age of treatment >60 years (HR=2.269, 95% CI 1.060‒4.860, P=0.035) and IPI scores of 3 to 5 (HR=2.557, 95%CI 1.132‒5.778, P=0.024) were independent factors affecting OS. For patients with relapsed/refractory DLBCL, salvage ASCT was found to significantly improve the prognosis of these patients and was a protective factor for the death event of patients (P=0.030). For patients in the high-risk group who achieved CR in the interim evaluation after chemotherapy, there were no deaths in patients on maintenance therapy with consolidation ASCT and rituximab to the end point of follow-up; however, it did not prolong the OS of the patients (P>0.05).Conclusion·In patients with relapsed/refractory DLBCL, salvage ASCT can significantly prolong the OS, whereas in the high-risk patients of DLBCL, consolidation ASCT and rituximab maintenance therapy can't prolong the OS

Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum

<p>Abstract</p> <p>Background</p> <p>Biochemical conversion of lignocellulose hydrolysates remains challenging, largely because most microbial processes have markedly reduced efficiency in the presence of both hexoses and pentoses. Thus, identification of microorganisms capable of efficient and simultaneous utilization of both glucose and xylose is pivotal to improving this process.</p> <p>Results</p> <p>In this study, we found that the oleaginous yeast strain <it>Trichosporon cutaneum </it>AS 2.571 assimilated glucose and xylose simultaneously, and accumulated intracellular lipid up to 59 wt% with a lipid coefficient up to 0.17 g/g sugar, upon cultivation on a 2:1 glucose/xylose mixture in a 3-liter stirred-tank bioreactor. In addition, no classic pattern of diauxic growth behavior was seen; the microbial cell mass increased during the whole culture process without any lag periods. In shake-flask cultures with different initial glucose:xylose ratios, glucose and xylose were consumed simultaneously at rates roughly proportional to their individual concentrations in the medium, leading to complete utilization of both sugars at the same time. Simultaneous utilization of glucose and xylose was also seen during fermentation of corn-stover hydrolysate with a lipid content and coefficient of 39.2% and 0.15 g/g sugar, respectively. The lipid produced had a fatty-acid compositional profile similar to those of conventional vegetable oil, indicating that it could have potential as a raw material for biodiesel production.</p> <p>Conclusion</p> <p>Efficient lipid production with simultaneous consumption of glucose and xylose was achieved in this study. This process provides an exciting opportunity to transform lignocellulosic materials into biofuel molecules, and should also encourage further study to elucidate this unique sugar-assimilation mechanism.</p

A CRISPR/Cas12a-assisted rapid detection platform by biosensing the apxIVA of Actinobacillus pleuropneumoniae

Actinobacillus pleuropneumoniae is an important respiratory pig pathogen that causes substantial losses in the worldwide swine industry. Chronic or subclinical infection with no apparent clinical symptoms poses a challenge for preventing transmission between herds. Rapid diagnostics is important for the control of epidemic diseases. In this study, we formulated an A. pleuropneumoniae species-specific apxIVA-based CRISPR/Cas12a-assisted rapid detection platform (Card) that combines recombinase polymerase amplification (RPA) of target DNA and subsequent Cas12a ssDNase activation. Card has a detection limit of 10 CFUs of A. pleuropneumoniae, and there is no cross-reactivity with other common swine pathogens. The detection process can be completed in 1 h, and there was 100% agreement between the conventional apxIVA-based PCR and Card in detecting A. pleuropneumoniae in lung samples. Microplate fluorescence readout enables high-throughput use in diagnostic laboratories, and naked eye and lateral flow test readouts enable use at the point of care. We conclude that Card is a versatile, rapid, accurate molecular diagnostic platform suitable for use in both laboratory and low-resource settings

Mesenchymal stem cell-derived exosomes can alleviate GVHD and preserve the GVL effect in allogeneic stem cell transplantation animal models

BackgroundMesenchymal stem cells (MSCs) can alleviate graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). MSCs-derived exosomes (MEXs) can mirror the biological function of their parent cells. Whether MEXs can alleviate GVHD like their parent cells or not is unclear. In this study, we investigate the effects of MEXs on GVHD and graft-versus-leukemia (GVL) effect in vitro and in HSCT animal models.MethodMSCs were produced using bone marrow mononuclear cells (MNCs), and MEXs were separated from the supernatants of MSCs. Electron microscopy, western blot, and nanoparticle tracking analysis (NTA) were used to determine the characteristics of MEXs. The immunomodulatory function of MEXs and their effects on GVHD and GVL were examined in vitro and in vivo.ResultLike other cell-type derived exosomes, our data revealed that MEXs were also disc-shaped vesicles with a diameter of 100–200 nm under electron microscopy and were positive for the exosomal hallmark proteins. MEXs can notably inhibit the expression of costimulatory molecules and functional cytokine secretion of dendritic cells (DCs). Meanwhile, MEXs can exert suppressive effects on T lymphocyte proliferation and activation. Moreover, MEXs can also encourage the polarization of macrophages toward the M2 type. In animal HSCT models, MEXs can promote the differentiation of Treg cells in spleens, decrease the GVHD score, increase the survival rate of mice, and preserve the cytotoxic antileukemia effects of CD8+ T lymphocytes from recipient mice.ConclusionThese findings showed that MEXs exert their effects by inhibiting the immunomodulatory function of DCs, macrophages, and T lymphocytes. In the animal model, MEXs ameliorate the clinical symptoms of GVHD, while maintaining the antitumor effects of CD8+ T lymphocytes. Therefore, it can be inferred that MEXs can separate GVHD from GVL in HSCT. Our study suggests that MEXs have broad clinical application potential in the prevention and treatment of GVHD in HSCT in the near future

Nucleotide-level prediction of CircRNA-protein binding based on fully convolutional neural network

Introduction: CircRNA-protein binding plays a critical role in complex biological activity and disease. Various deep learning-based algorithms have been proposed to identify CircRNA-protein binding sites. These methods predict whether the CircRNA sequence includes protein binding sites from the sequence level, and primarily concentrate on analysing the sequence specificity of CircRNA-protein binding. For model performance, these methods are unsatisfactory in accurately predicting motif sites that have special functions in gene expression.Methods: In this study, based on the deep learning models that implement pixel-level binary classification prediction in computer vision, we viewed the CircRNA-protein binding sites prediction as a nucleotide-level binary classification task, and use a fully convolutional neural networks to identify CircRNA-protein binding motif sites (CPBFCN).Results: CPBFCN provides a new path to predict CircRNA motifs. Based on the MEME tool, the existing CircRNA-related and protein-related database, we analysed the motif functions discovered by CPBFCN. We also investigated the correlation between CircRNA sponge and motif distribution. Furthermore, by comparing the motif distribution with different input sequence lengths, we found that some motifs in the flanking sequences of CircRNA-protein binding region may contribute to CircRNA-protein binding.Conclusion: This study contributes to identify circRNA-protein binding and provides help in understanding the role of circRNA-protein binding in gene expression regulation

Production of lipid from N-acetylglucosamine by Cryptococcus curvatus

N-Acetylglucosamine (GlcNAc), the monomeric constituent of chitin, is rarely used as a carbon source for fermentation technology. In this study, we demonstrate that the oleaginous yeast Cryptococcus curvatus ATCC 20509 can produce intracellular lipid during the cultivation process and total lipid content can reach 54% on a GlcNAc-based medium. Culture of C. curvatus under various conditions indicated that lipid accumulation also occurred at a relatively broad range of temperatures as well as relatively high initial GlcNAc concentrations. Fatty acid analysis indicated that the product was rich in palmitic acid, stearic acid, and oleic acid, closely resembling the composition of palm oil. More importantly, the lipid sample produced at 22 degrees C had a total saturated fatty acid content of 54.2 wt%, suggesting that it may be explored as cocoa-butter equivalent. Our data suggested that GlcNAc could be used as a feedstock for industrial biotechnology and that C. curvatus ATCC 20509 is a strain capable of accumulating high intracellular lipid using this nitrogen-rich renewable material

Lipid production by Rhodosporidium toruloides Y4 using different substrate feeding strategies

Lipid production by Rhodosporidium toruloides Y4 using different substrate feeding strategiesMicrobial lipid is a potential alternative feedstock for the biodiesel industry. New culture strategies remain to be developed to improve the economics of microbial lipid technology. This work describes lipid production by the oleaginous yeast Rhodosporidium toruloides Y4 using a 15-l bioreactor with different substrate feeding strategies. Among these strategies, the intermittent feeding mode gave a lipid productivity of 0.36 g l(-1) h(-1), whereas the constant glucose concentration II (CC-II) mode gave the highest lipid productivity of 0.57 g l(-1) h(-1). The repeated fed-batch mode according to the CC-II mode was performed with a duration time of 358 h, and the overall lipid productivity was 0.55 g l(-1) h(-1). Our results suggested that substrate feeding modes had a great impact on lipid productivity and that the repeated fed-batch process was the most appealing method by which to enhance microbial lipid production

Lipid production by Lipomyces starkeyi cells in glucose solution without auxiliary nutrients

Lipid production by Lipomyces starkeyi cells in glucose solution without auxiliary nutrientsTwo-stage fermentation process was used for lipid production by Lipomyces starkeyi AS 2.1560 in glucose solution without auxiliary nutrients. In the first stage, cells were cultivated in a nutrient-rich medium for propagation. In the second stage, cells were resuspended in glucose solution to achieve high cellular lipid contents. The effects of the inocula age, cell density and initial glucose concentration on lipid production were briefly studied. When high cell density fermentation was performed in a 7-L stirred-tank bioreactor for 40h using non-sterile glucose solution as carbon source, the biomass, lipid and lipid content reached 104.6 g/L, 67.9 g/L and 64.9%, respectively. More significantly, lipid productivity reached 2.0 g/L h during the initial 16 h-period and 1.6 g/L h for the entire culture. Our results demonstrated that cell propagation and lipid accumulation processes can be spatially separated, allowing further optimization to improve both processes. The two-stage fermentation method should have a great potential to develop more efficient processes to convert renewable materials into biofuel and related products. (C) 2011 Elsevier B.V. All rights reserved