资源环境科技发展态势分析平台

Bulk amorphous materials have been studied extensively and are widely used, yet their atomic arrangement remains an open issue. Although they are generally believed to be Zachariasen continuous random networks(1), recent experimental evidence favours the competing crystallite model in the case of amorphous silicon(2-4). In two-dimensional materials, however, the corresponding questions remain unanswered. Here we report the synthesis, by laser-assisted chemical vapour deposition(5), of centimetre-scale, free-standing, continuous and stable monolayer amorphous carbon, topologically distinct from disordered graphene. Unlike in bulk materials, the structure of monolayer amorphous carbon can be determined by atomic-resolution imaging. Extensive characterization by Raman and X-ray spectroscopy and transmission electron microscopy reveals the complete absence of long-range periodicity and a threefold-coordinated structure with a wide distribution of bond lengths, bond angles, and five-, six-, seven- and eight-member rings. The ring distribution is not a Zachariasen continuous random network, but resembles the competing (nano)crystallite model(6). We construct a corresponding model that enables density-functional-theory calculations of the properties of monolayer amorphous carbon, in accordance with observations. Direct measurements confirm that it is insulating, with resistivity values similar to those of boron nitride grown by chemical vapour deposition. Free-standing monolayer amorphous carbon is surprisingly stable and deforms to a high breaking strength, without crack propagation from the point of fracture. The excellent physical properties of this stable, free-standing monolayer amorphous carbon could prove useful for permeation and diffusion barriers in applications such as magnetic recording devices and flexible electronics.

Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment(1,2). Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells(3,4)and has a beneficial role in wound-healing responses(5,6). Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis(1,7). Accordingly, eliminating senescent cells from damaged tissues in mice ameliorates the symptoms of these pathologies and even promotes longevity(1,2,8-10). Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells can be effective senolytic agents. We identify the urokinase-type plasminogen activator receptor (uPAR)(11)as a cell-surface protein that is broadly induced during senescence and show that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo. CAR T cells that target uPAR extend the survival of mice with lung adenocarcinoma that are treated with a senescence-inducing combination of drugs, and restore tissue homeostasis in mice in which liver fibrosis is induced chemically or by diet. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases.

Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescent cells in vitro and in vivo and reduce liver fibrosis in mice.

Prostate cancer is the second most common cancer in men worldwide(1). Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients(2,3). However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.