Cytoplasmic chromatin triggers inflammation in senescence and cancer

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer

Epigenetic parameters such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. Global histone modification patterns have been implicated as possible predictors of cancer recurrence and prognoses in a great variety of tumor entities. Our study was designed to evaluate the association among trimethylated histone H3 at lysine 27 (H3K27me3), clinicopathological variables and outcome in early-stage non-small cell lung cancer (NSCLC). The expression of H3K27me3 and its methyltransferase, enhancer of zeste homolog 2 (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients (n=42). In addition, the specificity of antibody for H3K27me3 was tested by western blot analysis. The optimal cut-off point of H3K27me3 expression for prognosis was determined by the X-tile program. The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests. As a result, enhanced trimethylation of H3K27me3 was correlated with longer overall survival (OS) and better prognosis (P<0.05). Moreover, both univariate and multivariate analyses indicated that H3K27me3 level was a significant and independent predictor of better survival (hazard ratio, 0.187; 95% confidence interval, 0.066-0.531, P=0.002). Furthermore, H3K27me3 expression was positively correlated with DNA methylation level at CCGG sites while reversely related to EZH2 expression (P<0.05). In conclusion, H3K27me3 level defines unrecognized subgroups of NSCLC patients with distinct epigenetic phenotype and clinical outcome, and can probably be used as a novel predictor for better prognosis in NSCLC patients

Community Transformation and the Formation of Ethnic Capital: Immigrant Chinese Communities in the United States

AbstractIn this article, we attempt to develop a conceptual framework of “ethnic capital” in order to examine the dynamics of immigrant communities. Building on the theories of social capital and the enclave economy, we argue that ethnic capital is not a thing but involves interactive processes of ethnic-specific financial capital, human capital, and social capital. We use case studies of century-old Chinatowns and emerging middle-class immigrant Chinese communities in New York and Los Angeles to illustrate how ethnic capital affects community building and transformation, which in turn influence the social mobility of immigrants. We also discuss how developments in contemporary ethnic enclaves challenge the conventional notion of assimilation and contribute to our understanding of immigrant social mobility. </jats:sec

Evolution of the rural social security system in a large country over 35 years: institutional transformation and the Chinese experience

Purpose This paper aims to review the institutional evolution of China's rural social security system in the past 35 years, focusing on major policy transformations of the rural social security system in a large country, and extract the Chinese experience on developing rural social security.Design/methodology/approach This paper systematically reviews the evolution of rural social security system via organizing policy documents, key events and research literature on the construction of rural social security since the Reform and Opening-up.Findings First, institutional transformation is a profound change in China's rural social security system; second, policy transformation has taken place in the main areas of China's rural social security system, including rural endowment insurance, medical insurance and social assistance; third, the policy evolution of China's rural social security system has a unique experience in a large country.Originality/value China is the country with the largest rural population in the world. The process and experience of transforming the social security system in the vast rural areas of China have important value and reference significance for other developing countries.</jats:sec

Real-Time Thermal Infrared Tracking Based on Collaborative Online and Offline Method

Most tracking-by-detection based trackers employ the online model update scheme based on the spatiotemporal consistency of visual cues. In presence of self-deformation, abrupt motion and heavy occlusion, these trackers suffer from different attributes and are prone to drifting. The model based on offline training, namely Siamese networks is invariant when suffering from the attributes. While the tracking speed of the offline method can be slow which is not enough for real-time tracking. In this paper, a novel collaborative tracker which decomposes the tracking task into online and offline modes is proposed. Our tracker switches between the online and offline modes automatically based on the tracker status inferred from the present failure tracking detection method which is based on the dispersal measure of the response map. The present Real-Time Thermal Infrared Collaborative Online and Offline Tracker (TCOOT) achieves state-of-the-art tracking performance while maintaining real-time speed at the same time. Experiments are carried out on the VOT-TIR-2015 benchmark dataset and our tracker achieves superior performance against Staple and Siam FC trackers by 3.3% and 3.6% on precision criterion and 3.8% and 5% on success criterion, respectively. The present method is real-time tracker as well.</jats:p

Protocol for in vivo CRISPR knockout screening of autophagy genes to identify breast cancer metastasis suppressors

Summary: Metastasis represents the primary cause of mortality among patients with breast cancer. Here, we present a protocol for utilizing an in vivo custom CRISPR-Cas9 knockout library to systematically investigate autophagy regulatory genes implicated in breast cancer metastasis to the lung in mice. We describe steps for library synthesis, cloning, and virus packaging and transfection. We then detail procedures for genome DNA collection and transplantation, followed by analysis of screening data. This protocol enables efficient identification of potential suppressors of breast cancer metastasis in vivo.For complete details on the use and execution of this protocol, please refer to Hao et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Biomarker-responsive nanoprobe with aggregation-induced emission for locating and guiding resection of deep-seated tumors <i>via</i> optoacoustic and NIR fluorescence imaging

A nanoprobe responsive to specific biomarkers with aggregation-induced emission has been developed for locating and guiding resection of tumors via optoacoustic and fluorescence imaging.</p