No abstract

Ruptured and intact plasma membranes are classically considered as hallmarks of necrotic and apoptotic cell death, respectively. As such, apoptosis is usually considered a non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, revealed that plasma membrane rupture is mediated by MLKL channels during necroptosis but depends on non-selective gasdermin D (GSDMD) pores during pyroptosis. Importantly, the morphology of dying cells executed by MLKL channels can be distinguished from that executed by GSDMD pores. Interestingly, it was found recently that secondary necrosis of apoptotic cells, a previously believed non-regulated form of cell lysis that occurs after apoptosis, can be programmed and executed by plasma membrane pore formation like that of pyroptosis. In addition, pyroptosis is associated with pyroptotic bodies, which have some similarities to apoptotic bodies. Therefore, different cell death programs induce distinctive reshuffling processes of the plasma membrane. Given the fact that the nature of released intracellular contents plays a crucial role in dying/dead cell-induced immunogenicity, not only membrane rupture or integrity but also the nature of plasma membrane breakdown would determine the fate of a cell as well as its ability to elicit an immune response. In this review, we will discuss recent advances in the field of apoptosis, necroptosis and pyroptosis, with an emphasis on the mechanisms underlying plasma membrane changes observed on dying cells and their implication in cell death-elicited immunogenicity.

Recently, wearable pressure sensors have attracted tremendous attention because of their potential applications in monitoring physiological signals for human healthcare. Sensitivity and linearity are the two most essential parameters for pressure sensors. Although various designed micro/nanostructure morphologies have been introduced, the trade-off between sensitivity and linearity has not been well balanced. Human skin, which contains force receptors in a reticular layer, has a high sensitivity even for large external stimuli. Herein, inspired by the skin epidermis with high-performance force sensing, we have proposed a special surface morphology with spinosum microstructure of random distribution via the combination of an abrasive paper template and reduced graphene oxide. The sensitivity of the graphene pressure sensor with random distribution spinosum (RDS) microstructure is as high as 25.1 kPa in a wide linearity range of 0-2.6 kPa. Our pressure sensor exhibits superior comprehensive properties compared with previous surface-modified pressure sensors. According to simulation and mechanism analyses, the spinosum microstructure and random distribution contribute to the high sensitivity and large linearity range, respectively. In addition, the pressure sensor shows promising potential in detecting human physiological signals, such as heartbeat, respiration, phonation, and human motions of a pushup, arm bending, and walking. The wearable pressure sensor array was further used to detect gait states of supination, neutral, and pronation. The RDS microstructure provides an alternative strategy to improve the performance of pressure sensors and extend their potential applications in monitoring human activities.

The innovation on the low dimensional nanomaterials brings the rapid growth of nano community. Developing the controllable production and commercial applications of nanomaterials for sustainable society is highly concerned. Herein, carbon nanotubes (CNTs) with sp(2) carbon bonding, excellent mechanical, electrical, thermal, as well as transport properties are selected as model nanomaterials to demonstrate the road of nanomaterials towards industry. The engineering principles of the mass production and recent progress in the area of CNT purification and dispersion are described, as well as its bulk application for nanocomposites and energy storage. The environmental, health, and safety considerations of CNTs, and recent progress in CNT commercialization are also included. With the effort from the CNT industry during the past 10 years, the price of multi-walled CNTs have decreased from 45 000 to 100 $ kg(-1) and the productivity increased to several hundred tons per year for commercial applications in Li ion battery and nanocomposites. When the prices of CNTs decrease to 10 $ kg(-1) , their applications as composites and conductive fillers at a million ton scale can be anticipated, replacing conventional carbon black fillers. Compared with traditional bulk chemicals, the controllable synthesis and applications of CNTs on a million ton scale are still far from being achieved due to the challenges in production, purification, dispersion, and commercial application. The basic knowledge of growth mechanisms, efficient and controllable routes for CNT production, the environmental and safety issues, and the commercialization models are still inadequate. The gap between the basic scientific research and industrial development should be bridged by multidisciplinary research for the rapid growth of CNT nano-industry.

The recessive tall rice (Oryza sativa) mutant elongated uppermost internode (eui) is morphologically normal until its final internode elongates drastically at the heading stage. The stage-specific developmental effect of the eui mutation has been used in the breeding of hybrid rice to improve the performance of heading in male sterile cultivars. We found that the eui mutant accumulated exceptionally large amounts of biologically active gibberellins (GAs) in the uppermost internode. Mapbased cloning revealed that the Eui gene encodes a previously uncharacterized cytochrome P450 monooxygenase, CYP714D1. Using heterologous expression in yeast, we found that EUI catalyzed 16a,17-epoxidation of non-13-hydroxylated GAs. Consistent with the tall and dwarfed phenotypes of the eui mutant and Eui-overexpressing transgenic plants, respectively, 16a,17-epoxidation reduced the biological activity of GA 4 in rice, demonstrating that EUI functions as a GAdeactivating enzyme. Expression of Eui appeared tightly regulated during plant development, in agreement with the stagespecific eui phenotypes. These results indicate the existence of an unrecognized pathway for GA deactivation by EUI during the growth of wild-type internodes. The identification of Eui as a GA catabolism gene provides additional evidence that the GA metabolism pathway is a useful target for increasing the agronomic value of crops.

DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability, and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpT, and CpC (non-CpG) dinucleotides. Here we report a comprehensive analysis of non-CpG methylation in 76 genome-scale DNA methylation maps across pluripotent and differentiated human cell types. We confirm non-CpG methylation to be predominantly present in pluripotent cell types and observe a decrease upon differentiation and near complete absence in various somatic cell types. Although no function has been assigned to it in pluripotency, our data highlight that non-CpG methylation patterns reappear upon iPS cell reprogramming. Intriguingly, the patterns are highly variable and show little conservation between different pluripotent cell lines. We find a strong correlation of non-CpG methylation and DNMT3 expression levels while showing statistical independence of non-CpG methylation from pluripotency associated gene expression. In line with these findings, we show that knockdown of DNMTA and DNMT3B in hESCs results in a global reduction of non-CpG methylation. Finally, non-CpG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of cytosine methylation patterns in human cells using a large representative sample set.

Mixed lineage kinase domain-like protein (Mlkl) was recently found to interact with receptor interacting protein 3 (Rip3) and to be essential for tumor necrosis factor (TNF)-induced programmed necrosis (necroptosis) in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases (TALENs)-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell development. Mlkl-deficient mouse embryonic fibroblasts (MEFs) and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their ability to activate NF-κB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides (LPS), respectively. Consistently, Mlkl-deficient macrophages and mice exhibited normal interleukin-1β (IL-1β), IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.

Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIPbisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 trimethylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in Dnmt triple-knockout (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at a megabase scale. Our strategy provides a unique way of investigating global interdependencies between DNA methylation and other chromatin features.