Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical ...resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.
Scant understanding of the glioblastoma microenvironment and molecular bases hampers development of efficient treatment strategies. Analyses of gene signatures of human gliomas demonstrate that the ...SETD2 mutation is correlated with poor prognosis of IDH1/2 wild-type (IDH-WT) adult glioblastoma patients. To better understand the crosstalk between SETD2 mutant (SETD2-mut) glioblastoma cells and the tumor microenvironment, we leverage single-cell transcriptomics to comprehensively map cellular populations in glioblastoma. In this study, we identify a specific subtype of high-grade glioma-associated microglia (HGG-AM). Further analysis shows that transforming growth factor (TGF)-β1 derived from SETD2-mut/IDH-WT tumor cells activates HGG-AM, exhibiting pro-inflammation and proliferation signatures. Particularly, HGG-AM secretes interleukin (IL)-1β via the apolipoprotein E (ApoE)-mediated NLRP1 inflammasome, thereby promoting tumor progression. HGG-AM present extensive proliferation and infiltration to supplement the activated microglia pool. Notably, TGF-β1/TβRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.
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•A subset of high-grade glioma-associated microglia (HGG-AM) is identified by scRNA-seq•TGF-β1 activated from SETD2-mut/IDH-WT GBM cells promotes activation of HGG-AM•HGG-AM exhibits pro-inflammation and proliferation features, promoting tumor progression
Liu et al. find that high-grade glioma-associated microglia exhibit inflammasome-mediated pro-inflammatory and proliferative signatures shaping the cytokine microenvironment to promote oncogenesis.
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe ...resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints.
The intrinsic stability issues of organo-metal halide perovskite materials induced by moisture, heat, light and the presence of an electric field constitute big obstacles that are preventing ...perovskite solar cells (PSCs) from industrial application. Herein, we have demonstrated that when a hydrophobic organic acid molecule, 4-dimethylaminobenzoic acid, is introduced to modify the top surface of a CH3NH3PbI3 thin film, it is a facile way to simultaneously enhance the stability and efficiency of the corresponding PSCs. This surface modification can not only improve the perovskite film’s electronic quality but also provide it with a certain waterproofing capability. Accordingly, the efficiency of the inverted PSC is improved from 17.43% to 19.87%. More encouragingly, after 1 sun light soaking, 85 °C thermal aging, and high humidity (70%) aging for 1000 hours, the modified CH3NH3PbI3 based PSCs can retain 91%, 81% and 98% efficiency, respectively.
Tetragonal-to-monoclinic Bi4Ti3O12 (BIT) exhibits complicated domain patterns thanks to its two independently switchable spontaneous polarizations that lie in the ac plane of the monoclinic unit ...cell. Utilizing the nonlinear theory of ferroelectric phase transformation based on the deformation gradient tensor and spontaneous polarization, we systematically analyzed domain patterns in BIT, classifying its domain walls (DWs) into five different classes. Three-dimensional piezoresponse force microscopy (3D PFM) was then adopted to characterize the ceramic BIT, revealing intriguing domain patterns in planar, lateral, as well as tilted grains. Guided by the nonlinear theoretical analysis, 3D polarization distributions were successfully reconstructed, wherein 9°-, 90°-, 91°-, and 180°-DWs were observed along with 171°-charged DWs. The nonlinear analysis is thus confirmed by 3D PFM characterizations, and the combined theoretical analysis and experimental investigation contribute to our understanding on the 3D tetragonal-to-monoclinic ferroelectric domain patterns.
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Processing schedules for grain boundary engineering involving different types of cold deformation (tension, compression, and rolling) and annealing were designed and carried out for 18Mn18Cr0.6N high ...nitrogen austenitic stainless steel. The grain boundary characteristic distribution was obtained and characterized by electron backscatter diffraction (EBSD) analysis. The corrosion resistance of the specimens with different grain boundary characteristic distribution was examined by using potentiodynamic polarization test. The corrosion behavior of different types of boundaries after sensitization was also studied. The fraction of low-Σ boundaries decreased with increasing strain, and it was insensitive to the type of cold deformation when the engineering strain was lower than 20%. At the strain of 30%, the largest and smallest fractions of low-Σ boundaries were achieved in cold-tensioned and rolled specimens, respectively. The fraction of low-Σ boundaries increased exponentially with the increase of grain size. The proportion of low-angle grain boundaries increased with decreasing grain size. Increasing the fraction of low-Σ boundaries could improve the pitting corrosion resistance for the steels with the same grain size. After sensitization, the relative corrosion resistances of low-angle grain boundaries, Σ3 boundaries, and Σ9 boundaries were 100%, 95%, and 25%, respectively, while Σ27 boundaries, other low-Σ boundaries and random high-angle grain boundaries had no resistance to corrosion.
Abstract
Ever-increasing hardware capabilities and computation powers have enabled acquisition and analysis of big scientific data at the nanoscale routine, though much of the data acquired often ...turn out to be redundant, noisy and/or irrelevant to the problems of interest, and it remains nontrivial to draw clear mechanistic insights from pure data analytics. In this work, we use scanning probe microscopy (SPM) as an example to demonstrate deep data methodology for nanosciences, transitioning from brute-force analytics such as data mining, correlation analysis and unsupervised classification to informed and/or targeted causative data analytics built on sound physical understanding. Three key ingredients of such deep data analytics are presented. A sequential excitation scanning probe microscopy (SE-SPM) technique is first developed to acquire high-quality, efficient and physically relevant data, which can be easily implemented on any standard atomic force microscope (AFM). Brute-force physical analysis is then carried out using a simple harmonic oscillator (SHO) model, enabling us to derive intrinsic electromechanical coupling of interest. Finally, principal component analysis (PCA) is carried out, which not only speeds up the analysis by four orders of magnitude, but also allows a clear physical interpretation of its modes in combination with SHO analysis. A rough piezoelectric material has been probed using such a strategy, enabling us to map its intrinsic electromechanical properties at the nanoscale with high fidelity, where conventional methods fail. The SE in combination with deep data methodology can be easily adapted for other SPM techniques to probe a wide range of functional phenomena at the nanoscale.
Glioblastoma (GBM) is the most common and lethal malignant tumor of the central nervous system in adults. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited ...success in ameliorating patient survival. The immunosuppressive tumor microenvironment, which is infiltrated by a variety of myeloid cells, has been considered a crucial obstacle to current treatment. Recently, immunotherapy, which has achieved great success in hematological malignancies and some solid cancers, has garnered extensive attention for the treatment of GBM. In this review, we will present evidence on the features and functions of different populations of myeloid cells, and on current clinical advances in immunotherapies for glioblastoma.
It was discovered the application of Al
2
O
3
nanofluid as lubricant for steel hot rolling could synchronously achieve oxidation protection of strips surface. The underlying mechanism was ...investigated through hot rolling tests and molecular dynamics (MD) simulations. The employment of Al
2
O
3
nanoparticles contributed to significant enhancement in the lubrication performance of lubricant. The rolled strip exhibited the best surface topography that the roughness reached lowest with the sparsest surface defects. Besides, the oxide scale generated on steel surface was also thinner, and the ratio of Fe
2
O
3
among various iron oxides became lower. It was revealed the above oxidation protection effect of Al
2
O
3
nanofluid was attributed to the deposition of nanoparticles on metal surface during hot rolling. A protective layer in the thickness of about 193 nm was formed to prevent the direct contact between steel matrix and atmosphere, which was mainly composed of Al
2
O
3
and sintered organic molecules. MD simulations confirmed the diffusion of O
2
and H
2
O could be blocked by the Al
2
O
3
layer through physical absorption and penetration barrier effect.
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