46 research outputs found

    A new mathematical model for radiation cell killing mechanism: Target cumulating model

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    There are numerous mathematical or statistical models have been given out for radiation cell killing mechanism. Unfortunately, none of the model could explain the mechanism perfectly. The more advanced model for it is still necessary to be researched. Following common assumption, a new theoretical model named "target cumulating" model is induced from the molecular and particle physics level. The result of theoretical calculation gives the equation of cell survival rate corresponding to delivered dose and other sensitivity parameters. In addition to fit the cell survival curve well, the new model showed advantages with comparing to previous models. Also, the new model predicts or explains some phenomenon that had been observed in laboratory (e.g. dose rate effect and low dose hypersensitivity)

    Single-cell sequencing reveals CD133+CD44--originating evolution and novel stemness related variants in human colorectal cancer

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    BACKGROUND: Tumor heterogeneity of human colorectal cancer (CRC)-initiating cells (CRCICs) in cancer tissues often represents aggressive features of cancer progression. For high-resolution examination of CRCICs, we performed single-cell whole-exome sequencing (scWES) and bulk cell targeted exome sequencing (TES) of CRCICs to investigate stemness-specific somatic alterations or clonal evolution. METHODS: Single cells of three subpopulations of CRCICs (CD133+CD44+, CD133-CD44+, and CD133+CD44- cells), CRC cells (CRCCs), and control cells from one CRC tissue were sorted for scWES. Then, we set up a mutation panel from scWES data and TES was used to validate mutation distribution and clonal evolution in additional 96 samples (20 patients) those were also sorted into the same three groups of CRCICs and CRCCs. The knock-down experiments were used to analyze stemness-related mutant genes. Neoantigens of these mutant genes and their MHC binding affinity were also analyzed. FINDINGS: Clonal evolution analysis of scWES and TES showed that the CD133+CD44- CRCICs were the likely origin of CRC before evolving into other groups of CRCICs/CRCCs. We revealed that AHNAK2, PLIN4, HLA-B, ALK, CCDC92 and ALMS1 genes were specifically mutated in CRCICs followed by the validation of their functions. Furthermore, four predicted neoantigens of AHNAK2 were identified and validated, which might have applications in immunotherapy for CRC patients. INTERPRETATION: All the integrative analyses above revealed clonal evolution of CRC and new markers for CRCICs and demonstrate the important roles of CRCICs in tumorigenesis and progression of CRCs. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

    System-wide transcriptome damage and tissue identity loss in COVID-19 patients

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    The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung

    Microbialproperty improvement of saline-alkali soil for vegetable cultivation in Shanghai coastal area and its evaluation

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    In order to improve the fertility of saline-alkali soil in Shanghai coastal area,and make it suitable for vegetable cultiration,in the study,the saline-alkali soil was mixed with organic fertilizer,and then sprayed with composite microbes,which have the ability of the synergistically degrading organic substrate.The results showed that the saline-alkali soil added with 5∶1 organic fertilizer can rapidly increase the utilization ability soil organic matter.The soil microbial populations and microbial diversity index were significantly improved when applied with the 0.5% composite microbial liquid which containeds 1∶3∶3∶1 of Bacillus licheniformis,Pseudomonas sp., Flavobacterium sp.and Sphingomonas sp..At the same time,the enzymology indicators of soil urease,phosphatase,cellulase and catalase increased significantly.The vegetable cultivation experiments showed that:the biomass of Brassica chinensis nearly doubled in the original saline-alkali soil,while the yield of organic fertilizer increased 30.2% after 50 days.The research result on of the biological improvement for saline-alkali soil will have good application value in vegetable planting in coastal saline-alkali soil

    High-dose versus conventional-dose irradiation in cisplatin-based definitive concurrent chemoradiotherapy for esophageal cancer: a systematic review and pooled analysis

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    <div><p>We investigate whether high-dose (HD, ≥60 Gy) radiotherapy in definitive concurrent chemoradiotherapy (CCRT) based on cisplatin could yield benefits compared to conventional-dose (CD) CCRT. PubMed, Embase and Google Scholar were searched and data were pooled and analyzed for response rate, survival, failure patterns and toxicity. Results showed advantages in response rate, 5-year overall survival rate, local regional recurrence and distant failure rate compared to the CD arm with no difference in Grade ≥3 acute and late esophagitis, other toxicities were rare with moderate tolerance, subgroup analysis of squamous cell carcinoma also showed advantages for HD arm. We concluded that ≥60 Gy CCRT improved clinical outcomes compared to the CD arm, especially for esophageal squamous cell carcinoma. Our findings may provide a basis for future trials.</p></div

    SR-XRF analysis of Polytrichum in the Fildes Peninsula, Antarctica

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    In order to study the element contents and distribution of various mosses collected in the Antarctica, we analyzed the heavy elements of 3 species of Polytrichum in the Fildes Peninsula, P. alpinum, P. juniperinum and P. alpestre, by synchrotron radiation X-ray fluorescence (SR-XRF). The result shows that the elements, such as K, Ca, Mn, Fe, Cu, Zn and Sr, are nearly the same in Polytrichum. The peak intensity of K is higher than that of Ca, and the peak intensity of Ca is higher than that of Fe in P. alpinum. In P. juniperinum, the peak intensity of K is higher than that of Ca, and the peak intensity of Ca is close to that of Fe. The peak intensity of K is nearly equal to those of Ca and Fe in P. alpestre. Therefore, the habitats of 3 species of Polytrichum are similar in the Fildes Peninsula. By XRF analyzing of different parts of P. alpestre, we found that the peak intensities of relative concentration of elements are obviously different. The peak intensity of K in apical-bud is the highest in organism. The peak intensity ratio of K/Ca is 1.30, but they are below 1.0 in all the other parts. The peak intensity of Mn in pseudo-root is the highest in organism, and the peak intensity ration of Mn/Fe is 0.21, the biggest. In the parts of older leaf and pseudo-root, the ratios of Cu/Zn are 1.20 and 1.84 respectively, whereas they are less than 1 in the other parts. The element Br is seen specially in the older leaf and pseudo-root, that may result from the organs aged, and enhance the ability of anti-rottenness itself

    Genetic and epigenetic heterogeneity and the impact on cancer relapse.

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    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with an exceedingly poor prognosis: a 5-year overall survival rate of 40%-45% in the young and a 5-year survival rate of less than 10% in the elderly (\u3e60 years of age). Although a high percentage of patients enters complete remission after chemotherapeutic intervention, the majority of patients relapse within 3 years. Such stark prognostic outcomes highlight the need for additional clinical research, basic discovery, and molecular delineation of the etiologies and mechanisms behind responses to therapy that lead to relapse. Here, we summarize recent discoveries in tumor heterogeneity at the genetic and epigenetic levels and their independent molecular trajectories and dynamics in response to therapy. These new discoveries may have significant implications for understanding, monitoring, and treating leukemia and other cancers. Exp Hematol 2017 Oct; 54:26-30
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