Optimal combination of MYCN differential gene and cellular senescence gene predicts adverse outcomes in patients with neuroblastoma

IntroductionNeuroblastoma (NB) is a common extracranial tumor in children and is highly heterogeneous. The factors influencing the prognosis of NB are not simple.MethodsTo investigate the effect of cell senescence on the prognosis of NB and tumor immune microenvironment, 498 samples of NB patients and 307 cellular senescence-related genes were used to construct a prediction signature.ResultsA signature based on six optimal candidate genes (TP53, IL-7, PDGFRA, S100B, DLL3, and TP63) was successfully constructed and proved to have good prognostic ability. Through verification, the signature had more advantages than the gene expression level alone in evaluating prognosis was found. Further T cell phenotype analysis displayed that exhausted phenotype PD-1 and senescence-related phenotype CD244 were highly expressed in CD8+ T cell in MYCN-amplified group with higher risk-score.ConclusionA signature constructed the six MYCN-amplified differential genes and aging-related genes can be used to predict the prognosis of NB better than using each high-risk gene individually and to evaluate immunosuppressed and aging tumor microenvironment

Immune checkpoint alterations and their blockade in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a highly contagious disease that seriously affects people’s lives. Immune dysfunction, which is characterized by abnormal expression of multiple immune checkpoint proteins (ICs) on immune cells, is associated with progression and poor prognosis for tumors and chronic infections. Immunotherapy targeting ICs has been well established in modulating immune function and improving clinical outcome for solid tumors and hematological malignancies. The role of ICs in different populations or COVID-19 stages and the impact of IC blockade remains unclear. In this review, we summarized current studies of alterations in ICs in COVID-19 to better understand immune changes and provide strategies for treating COVID-19 patients, particularly those with cancer

Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy

Abstract In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave of immunotherapy targets that show great promise for use in the treatment of solid tumors and leukemia. To promote the research and clinical application of ICBs directed at these targets, we summarize their discovery, immunotherapy mechanism, preclinical efficiency, and clinical trial results in this review

Novel Spiral Silicon Drift Detector with Equal Cathode Ring Gap and Given Surface Electric Fields

Since the advent of semiconductor detectors, they have been developed for several generations, and their performance has been continuously improved. In this paper, we propose a new silicon drift detector structure that is different from the traditional spiral SDD structure that has a gap between the cathode ring and the width of cathode ring, increasing gradually with the increase of the radius of the cathode ring. Our new structure of spiral SDD structure has equal cathode ring gap and a given surface electric field, which has many advantages compared with the traditional structure. The novel SDD structure controllably reduces the area of silicon oxide between the spiral rings, which in turn reduces the surface leakage current due to the reduction of total oxide charge in the silicon oxide and electronic states on the silicon/silicon oxide interface. Moreover, it has better controllability to adjust this spiral ring cathode gap to achieve better surface electric field distribution, thus realizing the optimal carrier drift electric field and achieving the optimal detector performance. In order to verify this theory, we have modeled this new structure and simulated its electrical properties using the Sentaurus TCAD tool. We have also analyzed and compared different spiral ring cathode gap structures (from 10 µm to 25 µm for the gap). According to the simulation results of potential, electric field, and electron concentration, we have obtained that a spiral ring cathode gap of 10 µm has the best electrical characteristics, more uniform distribution of potential and surface electric field, and a more smooth and straight electron drift channel

Preparation and characterization of the hydrogen storage activated carbon from coffee shell by microwave irradiation and KOH activation

Coffee shell is an environmental concern to china along with steady growth of coffee production. This study attempt to characterize high specific surface area activated carbon (HSSA-AC). HSSA-AC was prepared from carbonized material which obtained from coffee shell by microwave irradiation. Textural properties and surface chemistry of HSSA-AC were found to be strongly depending on the activation time, KOH/C ratio and particle size. The textural properties of the samples were investigated by means of scanning electron microscope analyzer (SEM), cryogenic N2 adsorption, whereas, surface chemistry was probed through Fourier Transform Infrared (FTIR) spectrometer (Maldhure and Ekhe, 2011) and Hydrogen storage performance was tested by H2 adsorption. Maximum surface area of 3149 m2 g−1, Iodine adsorption value 2566 mg/g, Methylene Blue adsorption value 47.5 mL 0.1 g−1, the hydrogen adsorption value 0.91 wt% at 14 MPa and yield 39% was observed in case of microwave treated sample at activation time 9 min, KOH/C ratio 5 and particle size 0.25–0.71 mm. Results revealed usefulness of microwave treatment in influencing surface area of HSSA-AC which could be used in a hydrogen storage material research application

Memory T cells skew toward terminal differentiation in the CD8+ T cell population in patients with acute myeloid leukemia

Abstract Stem cell memory T (TSCM) and central memory T (TCM) cells can rapidly differentiate into effector memory (TEM) and terminal effector (TEF) T cells, and have the most potential for immunotherapy. In this study, we found that the frequency of TSCM and TCM cells in the CD8+ population dramatically decreased together with increases in TEM and TEF cells, particularly in younger patients with acute myeloid leukemia (AML) (< 60 years). These alterations persisted in patients who achieved complete remission after chemotherapy. The decrease in TSCM and TCM together with the increase in differentiated TEM and TEF subsets in CD8+ T cells may explain the reduced T cell response and subdued anti-leukemia capacity in AML patients

Image_3_Single-cell profiling of T cells uncovers a tissue-resident memory-like T-cell subset associated with bidirectional prognosis for B-cell acute lymphoblastic leukemia.tif

IntroductionThe character and composition of leukemia-related T cells are closely related to the treatment response and prognosis for patients. Though B cell-acute lymphoblastic leukemia (B-ALL) patients have benefited from immune-based approaches, such as chimeric antigen receptor T cells therapy, some of them still end with poor prognosis, especially for adult patients. Therefore, deep understanding of the developmental relationship between T cell subtypes in relation to B-ALL patient prognosis is urgently needed.MethodsWe analyzed the peripheral blood T cell single-cell RNA sequencing data of three B-ALL patients, using data from 11 healthy individuals as controls. In total, 16,143 and 53,701 T cells from B-ALL patients and healthy adults, respectively, were objectively analyzed for detailed delineation of 13 distinct T cell clusters. Cluster-specific genes were used as marker genes to annotate each T cell subtype.ResultsUnbiased analysis enabled the discovery of circulating CD103+ T cell (CD3+CD103+MKI67+), also defined as tissue-resident memory-like T (Trm-like) cell, populations were elevated in B-ALL patients, which expressed high level of cell proliferation and exhaustion related genes. In addition, cell fate trajectory analysis showed these Trm-like cells, which shared T-cell receptor (TCR) clonotypes with exhausted T (Tex) cells and effector T (Teff) cells, were supposed to transition into Teff cells; however, mainly transformed into Tex cells in leukemia environment. More importantly, Trm-like cells transformation into Teff cells and Tex cells potentially led to favorable or poor prognosis for B-ALL patients, respectively.ConclusionIn sum, a circulating Trm-like cell subset with high level expression of cell proliferation and exhaustion related genes was elevated in B-ALL patients. The bidirectional developmental potential of these T cells into Teff or Tex is closely associated with favorable or poor prognosis, respectively. Together, our study provided a unique insight of alteration of leukemia related T cells, also showed a potential immunotherapy direction and prognosis assessment model for B-ALL patients.</p