A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells

Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5′-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model

Size effect investigation of indentation response of stifffilm/compliant substrate composite structure

The stifffilm/compliant substrate composite structure with a high modulus ratio finds a wide range of applications in production and in scientific research, and its indentation behavior cannot be described by the traditional theory when the film thickness is reduced from the millimeter scale to the micrometer or nanometer scale. In order to better understand the trans-scale indentation response of the composite structure caused by the reduction in the film thickness, this problem is solved analytically with the strain gradient theory and integral transformation. The gradient effect on the indentation response of the system is assessed in detailed from three aspects: load-displacement relationship, surface topography and distribution of bending moment on the film. In addition, the influences of film thickness, modulus ratio of the film to the substrate, contact radius and Poisson's ratio on the gradient effect are investigated. It is found that the gradient effect on the indentation response of the system, which is not sensitive to the contact radius and Poisson's ratio, is related not only to the film thickness but also to the modulus ratio of the film to the substrate. Based on the above analysis, a dimensionless number (g/l) is proposed to evaluate the gradient effect on the indentation behaviors of the system. And with the help of the dimensionless number, a new simple and accurate method for measuring the material length scale is proposed. Our research provides a theoretical basis for an in-depth understanding of the gradient effects on the indentation response of the stifffilm/compliant substrate system and for the measurement of the material length scale. (C) 2020 Elsevier Ltd. All rights reserved

Prediction of the initial thickness of shear band localization based on a reduced strain gradient theory

AbstractPlastic flow localization in ductile materials subjected to pure shear loading and uniaxial tension is investigated respectively in this paper using a reduced strain gradient theory, which consists of the couple-stress (CS) strain gradient theory proposed by Fleck and Hutchinson (1993) and the strain gradient hardening (softening) law (C–W) proposed by Chen and Wang (2000). Unlike the classical plasticity framework, the initial thickness of the shear band and the strain rate distribution in both cases are predicted analytically using a bifurcation analysis. It shows that the strain rate is obviously non-uniform inside the shear band and reaches a maximum at the center of the shear band. The initial thickness of the shear band depends on not only the material intrinsic length lcs but also the material constants, such as the yield strength, ultimate tension strength, the linear hardening and softening shear moduli. Specially, in the uniaxial tension case, the most possible tilt angle of shear band localization is consistent qualitatively with the existing experimental observations. The results in this paper should be useful for engineers to predict the details of material failures due to plastic flow localization

Prediction of the initial thickness of shear band localization based on a reduced strain gradient theory

a b s t r a c t Plastic flow localization in ductile materials subjected to pure shear loading and uniaxial tension is investigated respectively in this paper using a reduced strain gradient theory, which consists of the couplestress (CS) strain gradient theory proposed by Fleck and Hutchinson (1993) and the strain gradient hardening (softening) law (C-W) proposed by Chen and Wang (2000). Unlike the classical plasticity framework, the initial thickness of the shear band and the strain rate distribution in both cases are predicted analytically using a bifurcation analysis. It shows that the strain rate is obviously non-uniform inside the shear band and reaches a maximum at the center of the shear band. The initial thickness of the shear band depends on not only the material intrinsic length l cs but also the material constants, such as the yield strength, ultimate tension strength, the linear hardening and softening shear moduli. Specially, in the uniaxial tension case, the most possible tilt angle of shear band localization is consistent qualitatively with the existing experimental observations. The results in this paper should be useful for engineers to predict the details of material failures due to plastic flow localization

Author Correction: Improved ethanol electrooxidation performance by shortening Pd-Ni active site distance in Pd-Ni-P nanocatalysts.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Distinct associations between hypertension and obstructive sleep apnea in male and female patients.

Obstructive sleep apnea (OSA) is highly associated with hypertension. However, the correlation between hypertension and OSA at different levels of severity and the influence of gender on that correlation are unclear. A total of 996 patients (776 males and 190 females) with OSA were recruited. The influence of gender on the correlation between hypertension and OSA at different stratifications of severity, based on the apnea-hypopnea index (AHI), was fully evaluated together with the major health risk factors obesity, age, and diabetes. Females with OSA were significantly older on average than males with OSA. Moreover, females had milder degrees of OSA on average than the extent of severity seen in males. The proportion of females with diabetes or hypertension was higher than that of males. The proportion of males with hypertension and obesity increased significantly with OSA, and age also increased with OSA. The percentage of females with hypertension at different degrees of OSA severity was stable at about 26% in the mild, moderate, and severe OSA groups. Among females, age was increased significantly in the moderate relative to the mild OSA group. Moreover, the proportion of obese subjects was increased significantly in the severe compared with the moderate OSA group. The proportions of males and females with diabetes were not significantly different among all OSA severity groups. An ordinal multivariate logistic regression analysis confirmed that hypertension, age, and obesity were associated with OSA severity in males, whereas only age and obesity were associated with OSA severity in females. Although the proportion of subjects with hypertension was higher in females with OSA than in males with OSA, the proportion of subjects with hypertension increased as the severity of OSA increased in males but not in females

Role of Epidermal Growth Factor Receptor-Specific CAR-T Cells in the Suppression of Esophageal Squamous Cell Carcinoma

ESCC is a highly malignant tumor, and its morbidity and mortality in China account for more than 50% of the world’s total rates. As effective treatments are lacking, the 5-year survival rate of patients does not exceed 30%. CAR-T-cell-based immunotherapy has emerged as one of the most promising cancer treatments; however, there are relatively fewer reports regarding its application for ESCC. In this study, we conducted large-sample whole-genome sequencing (WGS) and RNA-seq analysis of patients with ESCC from China to examine the feasibility of EGFR-targeting CAR-T cells in the treatment of ESCC. We found much higher levels of EGFR gene amplification and overexpression in tumors than in the normal tissues, indicating that EGFR could be a promising target of CAR-T-cell-based immunotherapy in ESCC. Therefore, we tested EGFR-targeting CAR-T cells for lytic activity against ESCC cells as a model to establish cellular immunotherapy for ESCC. Five types of CAR-T cells targeting EGFR were constructed, two of which, CAR1-T and CAR2-T, showed a strong cytotoxicity against ESCC in in vitro and in vivo experiments. The results of this study suggest that CAR1-T and CAR2-T have the potential to be used for anti-ESCC immunotherapy in clinics

Embedding Nanocluster in MOF via Crystalline Ion-Triggered Growth Strategy for Improved Emission and Selective Sensing

Metal–organic frameworks (MOFs) containing metal nanoclusters (NCs) display great potentials, but the fabrication faces challenges because of the serious agglomeration of NCs during the MOF growth. We report a crystalline ion-triggered growth strategy for embedding AuNCs in ZIF-8. As control, when the encapsulation was triggered with other metal ions (e.g., Ca²⁺, Pb²⁺, Cd²⁺, Na⁺, Fe³⁺, Cu²⁺, and Ni²⁺), the AuNCs failed to be encapsulated. The quantum yields and lifetime of AuNCs were greatly enhanced after embedding in ZIF-8. The AuNCs@ZIF-8 were then successfully applied for the selective sensing of H₂S both in liquid and gas phases. This crystalline ion-triggered growth strategy was easily extended to other systems, such as AgNCs@ZIF-8 and AuNCs@ZIF-67, indicating the general adaptability of this design protocol