Insights into the hierarchical structure and digestion rate of alkali-modulated starches with different amylose contents

Combined analytical techniques were used to explore the effects of alkali treatment on the multi-scale structure and digestion behavior of starches with different amylose/amylopectin ratios. Alkali treatment disrupted the amorphous matrix, and partial lamellae and crystallites, which weakened starch molecular packing and eventually enhanced the susceptibility of starch to alkali. Stronger alkali treatment (0.5% w/w) made this effect more prominent and even transformed the dual-phase digestion of starch into a triple-phase pattern. Compared with high-amylose starch, regular maize starch, which possesses some unique structure characteristics typically as pores and crystallite weak points, showed evident changes of hierarchical structure and in digestion rate. Thus, alkali treatment has been demonstrated as a simple method to modulate starch hierarchical structure and thus to realize the rational development of starch-based food products with desired digestibility

Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC

Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML

Long-time behavior of numerical solutions to nonlinear fractional ODEs

In this work, we study the long time behavior, including asymptotic contractivity and dissipativity, of the solutions to several numerical methods for fractional ordinary differential equations (F-ODEs). The existing algebraic contractivity and dissipativity rates of the solutions to the scalar F-ODEs are first improved. In order to study the long time behavior of numerical solutions to fractional backward differential formulas (F-BDFs), two crucial analytical techniques are developed, with the first one for the discrete version of the fractional generalization of the traditional Leibniz rule, and the other for the algebraic decay rate of the solution to a linear Volterra difference equation. By means of these auxiliary tools and some natural conditions, the solutions to F-BDFs are shown to be contractive and dissipative, and also preserve the exact contractivity rate of the continuous solutions. Two typical F-BDFs, based on the Grünwald–Letnikov formula and L1 method respectively, are studied. For high order F-BDFs, including convolution quadrature schemes based on classical second order BDF and product integration schemes based on quadratic interpolation approximation, their numerical contractivity and dissipativity are also developed under some slightly stronger conditions. Numerical experiments are presented to validate the long time qualitative characteristics of the solutions to F-BDFs, revealing very different decay rates of the numerical solutions in terms of the the initial values between F-ODEs and integer ODEs and demonstrating the superiority of the structure-preserving numerical methods

Correlation between subsets of tumor-infiltrating immune cells and risk stratification in patients with cervical cancer

Aim To investigate the correlation between clinicopathological features and risk stratification in cervical cancer patients, and evaluate the feasibility of tumor-infiltrating immune cells as prognostic biomarkers in clinical practice. Methods CD3+ tumor infiltrating T cells (TILs), CD45RO+ TILs, CD4+ TILs, CD8+ TILs, FOXP3+ TILs (regulatory T cells, Tregs), CD68+ tumor associated macrophages (TAMs), CD163+ TAMs, and PD-L1+ tumor cells were immunostained in formalin-fixed paraffin-embedded (PPFE) tissues from 96 cervical cancer patients. Immunostaining density and other clinicopathological features such as age, FIGO stage, histopathologic type, Ki67 index, HPV status, lymhovasular invasion status (LVI), lymph node metastasis, tumor size, stromal invasion status, surgical margin status, and parametrial invasion, were evaluated for their roles in risk stratification of cervical cancer patients. Results The results showed that significant differences of lymph node metastasis (p = 0.003), surgical margin status (p = 0.020), and stromal invasion status (p = 0.004) existed between lVI(−) and LVI(+) patients. CD3+ TILs in the central tumor area (p = 0.010), CD4+ TILs in the central tumor area (p = 0.045), CD8 + TILs in the central tumor area (p = 0.033), and CD8+ TILs in the invasive margin area (p = 0.004) showed significant differences between lVI(−) and LVI(+) patients. When patients were grouped by status of lymph node metastasis, significant differences of FIGO stage (p = 0.005), LVI status (p = 0.003), CD3+ TILs in the central tumor area (p = 0.045), CD45RO+ TILs in the central tumor area (p = 0.033), and CD45RO+ TILs in the invasive margin area (p = 0.028) were also observed. After the patients were stratified into low-, intermediate-, and high risk groups, significant differences of FIGO stage (p = 0.018), status of lymph node metastasis (p = 0.000), LVI status (p = 0.000), parametrial invasion status (p=0.012), stromal invasion status (p = 0.000), tumor growth pattern (p = 0.015) and tumor size (p = 0.000) were identified among 3 groups of patients, while only CD45RO+ TILs in the invasive margin area (p = 0.018) and FOXP3+ TILs in the central tumor area (p = 0.009) were statistically different among three groups of patients. Spearman’s correlation analysis demonstrated that FIGO stage, LVI status, status of lymph node metastasis, parametrial invasion, stromal invasion status, and tumor size positively correlated with risk stratification (P = 0.005, 0.020, 0.000, 0.022, 0.000, and 0.000 respectively), while CD45RO+ TILs in the invasive margin area and FOXP3+ TILs in the central tumor area showed statistically negative correlation with risk stratification (P = 0.031, 0.009 respectively). Conclusion Our study suggested that CD45RO+ TILs in the invasive margin area and FOXP3+ TILs in the central tumor area might be useful biomarkers for risk stratification in cervical cancer patients. Large cohort studies of cervical cancer patients are required to validate our hypothesis

Accounting entities in culture

The bachelor thesis on Accounting entities in culture deals with the accounting entities in the field of culture, especially with theatres. Its intention is to describe the historical development of these entities and their effective legislation in 2014, to determine their main resources of financing and to answer the question: What is the situation of private theatres in the Czech Republic? The theoretical part is focused on defining entities (theatres) in the field of culture and their historical development. It further describes legal conditions for doing business in the field of culture under commercial law and defines the types of legal forms of business in the Czech Republic. The following section analyses the specifics of the companies operating in the field of culture in terms of sales for tickets and financing of these entities in the form of grants. The practical part is focused on analysis of financial statements of 10 theatres in the Czech Republic in terms of quality reporting. In particular financial statements is analysed financial position and financial management of private theatres. In conclusion there is a brief assessment of the fulfilment of the objectives of the thesis

A further understanding of the multi-scale supramolecular structure and digestion rate of waxy starch

This work concerns how the multi-scale supramolecular structure of starch relates to its digestion rate from a view of structural heterogeneity. The untreated granule starch displayed a dual-phase digestion pattern, ascribed to two digestible fractions within the heterogeneous multi-scale structure of starch, which had prominently different digestion rates. Not only amorphous starch but also part of molecular orders (crystallites with flaws) were digested at a same rate k1 at the first phase; densely-assembled starch including orders with fewer flaws was digested at a rather slow rate k2 (ca. 2/5 of k1) at the second phase. When alkali altered the heterogeneous supramolecular structure of starch, the digestion behaviors were also changed. The 0.1% (w/v) alkali solution slightly disrupted the starch multi-scale structure, which reduced the molecular orders, disrupted the lamellae, weakened the molecular organization within growth rings, and enlarged the granule pores. Then, part of resistant starch was transformed into slowly-digestible fraction with a digestion rate close to k2. In contrast, when stronger (0.5% w/v) alkali was used, the starch multi-scale structure was more apparently disrupted, causing even granule swelling. This structural change resulted in a triple-phase digestion with three different digestion rates. Moreover, especially with stronger alkali, along with the structural disruption, some orders with a higher thermal stability emerged and reduced the accessibility of starch molecules to the enzyme. In this case, the digestion rate decreased with the treatment time

Validation of the 2018 FIGO Staging System for Predicting the Prognosis of Patients With Stage IIIC Cervical Cancer

Background: Risk stratification of patients with cervical cancer accompanied by positive lymph nodes (stage IIIC) (the 2018 International Federation of Gynecology and Obstetrics [FIGO] new staging system) yields a clinically heterogeneous group. In this study, we investigated the prognostic performance of the 2018 FIGO staging system for stage IIIC cervical cancer. Methods: The study included patients with stage III cervical cancer based on the 2018 FIGO staging system, who visited Chongqing University Cancer Hospital between January 2011 and December 2014. Kaplan-Meier curves were generated to evaluate overall survival (OS), which was compared using the log-rank test. The Cox proportional hazard regression model was used for multivariable analysis. Results: A total of 418 patients were eligible for analysis. The 5-year OS was 54.1% for stage IIIC1, 43.3% for stage IIIA, 40.6% for stage IIIB, and 23.1% for stage IIIC2 ( P 2 than in patients with stage IIIC1pN1-2 (HR 2.753, 95% CI 1.527-4.965, P = .001). Conclusions: Patients with stage IIIC1 cervical cancer showed heterogeneous clinical characteristics that reflected variable prognoses, depending on the T stage and the extent of pelvic lymph node metastases