SUMMARY Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration.

Novel flowerlike VO 2 (B) micro-nanostructures assembled by single-crystalline nanosheets have been successfully synthesized via a hydrothermal route using polymer polyvinyl pyrrolidone (PVP, K30) as capping reagent. Detailed proofs indicated that the process of crystal growth was dominated by a nucleation and growth, self-assembly, and then Ostwald ripening growth mechanism. For the first time, the flowerlike micronanostructures VO 2 (B) was applied as the active material into aqueous lithium ion battery applications, which showed improved electrochemical properties with the first discharge capacity reaching 74.9 mAhg -1 , a quite outstanding value for aqueous lithium ion battery systems in light of previous reports (usually <65 mAhg -1 ). In addition, corresponding VO 2 (B) nanostructures with better crystallinity were obtained by calcining the precursor of flowerlike VO 2 (B) structures. The post-treated flowerlike VO 2 (B) electrode shows fascinating advantages in electrochemical properties with the first discharge capacity reaching 81.3 mAhg -1 , which is higher than that of the flowerlike VO 2 (B) sample before annealing. Furthermore, we have investigated the electrochemical intercalation and deintercalation properties with Li + the synthesized VO 2 (B) nanobelts and carambola-like VO 2 (B) structure. The unique flowerlike structure plays a basic role in the morphology requirement to serve as transport paths for lithium ion in aqueous lithium ion batteries. It was observed that the morphologies and crystallinity of the synthesized products had an evident influence on the electrochemical intercalation and deintercalation properties with lithium ions.

Using the stopped-flow circular dichroism (SFCD) technique, we investigate the kinetics of the pH-induced folding and unfolding process of the DNA i-motif. The results show that the molecule can fold or unfold on a time scale of 100 ms when the solution pH is changed. It is also found that the folding and unfolding rates strongly depend on the solution pH. On the basis of quantitative data, we propose theoretical models to decipher the folding and unfolding kinetics. Our models suggest that the cooperativity of protons is crucial for both the folding and unfolding process. In the unfolding process, the cooperative neutralization of two protons (out of the total six protons in the i-motif molecule) is the only rate-limiting step. In the folding process, there exists a critical step in which three protons bind cooperatively to the DNA strand. These results offer an in-depth understanding of the folding and unfolding kinetics of the DNA i-motif and may give precise guidance for constructing novel nanodevices based on the DNA i-motif.

This communication reports a DNA tetrahedron whose self-assembly is triggered by an acidic environment. The key element is the formation/dissociation of a short, cytosine (C)-containing, DNA triplex. As the solution pH value oscillates between 5.0 and 8.0, the DNA triplex will form and dissociate that, in turn, leads to assembly or disassembly of the DNA tetrahedron, which has been demonstrated by native polyacrylamide gel electrophoresis (PAGE). We believe that such environment-responsive behavior will be important for potential applications of DNA nanocages such as on-demand drug release.

These findings indicated that increased uric acid levels probably associated with obesity and type 2 diabetes, and more definite research is needed to define any role for uric acid in relation to these diseases.

Background: In this study, we retrospectively summarized the differences of molecular gene mutations between MDS and AML patients, as well as the young and older age groups of MDS and AML patients. We also analyzed the response of newly diagnosed AML patients to standard DA or IA induction chemotherapy and the relationship between the chemotherapy outcome and the frequency of different gene mutation abnormalities. Methods: NGS assay covering 43 genes was studied in 93 de novo MDS and 325 non-M3 AML patients. Bone marrow samples from all patients underwent gene mutational analysis by NGS. Results: At least one non-synonymous gene mutation was detected in 279 AML patients (85.8%) and 85 MDS patients (91.4%). Contrary to 59 years and younger AML patients, there was a significantly higher incidence of gene mutation in 60 years and older AML patients (2.37 vs 1.94, p = 0.034). Gene mutation incidence in 60 years and older MDS patients increased, but no statistical significance was present (1.95 vs 1.64, p = 0.216). AML patients had a significantly higher gene mutation incidence compared with MDS-MLD patients (2.02 vs 1.63, p = 0.046). Gene mutation incidence was higher in patients with MDS-EB1/EB2 compared with patients with MDS-MLD but there was no statistical significance present (2.14 vs 1.63, p = 0.081). AML patients had significantly higher incidences of CEBPA, FLT3-ITD, DNMT3A, NPM1 and IDH1/2 gene mutations (p = 0.0043, 0.000, 0.030962, 0.002752, and 0.000628, respectively) and a lower incidence of TET2 and U2AF1 gene mutations (p = 0.000004 and 0.000, respectively) compared with MDS patients. Among the individual genes in different age groups, there were significantly higher incidences of RUNX1, IDH2, TP53 and SF3B1 gene mutations (p = 0.0478, 0.0028, 0.0024 and 0.005, respectively) as well as a trend of higher ASXL gene mutation (p = 0.057) in 60 years and older AML patients compared to 59 years and younger patients. There was no statistically significant difference in MDS patients with the different age groups and among the individual genes. Between AML patients and MDS patients among the different gene functional groups, AML patients had a significantly higher incidence of transcriptional deregulation (27.4% vs 15.1%, p = 0.014963), activated signalling (36.3% vs 10.8%, p = 0.000002) related gene mutations as well as a significantly lower incidence of RNA spliceosome (6.15% vs 60.1%, p = 0.000) related gene mutations. Furthermore, among the patients who received either IA or DA regimen

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Background Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. Methods Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts. Results We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets. Conclusion Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.