Inhibition of EZH2 Promotes Human Embryonic Stem Cell Differentiation into Mesoderm by Reducing H3K27me3.

Mesoderm derived from human embryonic stem cells (hESCs) is a major source of the mesenchymal stem/stromal cells (MSCs) that can differentiate into osteoblasts and chondrocytes for tissue regeneration. While significant progress has been made in understanding of molecular mechanisms of hESC differentiation into mesodermal cells, little is known about epigenetic factors controlling hESC fate toward mesoderm and MSCs. Identifying potential epigenetic factors that control hESC differentiation will undoubtedly lead to advancements in regenerative medicine. Here, we conducted an epigenome-wide analysis of hESCs and MSCs and uncovered that EZH2 was enriched in hESCs and was downregulated significantly in MSCs. The specific EZH2 inhibitor GSK126 directed hESC differentiation toward mesoderm and generated more MSCs by reducing H3K27me3. Our results provide insights into epigenetic landscapes of hESCs and MSCs and suggest that inhibiting EZH2 promotes mesodermal differentiation of hESCs

TRAF5 Is a Downstream Target of MAVS in Antiviral Innate Immune Signaling

The recognition of nucleic acids by the innate immune system during viral infection results in the production of type I interferons and the activation of antiviral immune responses. The RNA helicases RIG-I and MDA-5 recognize distinct types of cytosolic RNA species and signal through the mitochondrial protein MAVS to stimulate the phosphorylation and activation of the transcription factors IRF3 and IRF7, thereby inducing type I interferon expression. Alternatively, the activation of NF-κB leads to proinflammatory cytokine production. The function of MAVS is dependent on both its C-terminal transmembrane (TM) domain and N-terminal caspase recruitment domain (CARD). The TM domain mediates MAVS dimerization in response to viral RNA, allowing the CARD to bind to and activate the downstream effector TRAF3. Notably, dimerization of the MAVS CARD alone is sufficient to activate IRF3, IRF7, and NF-κB. However, TRAF3-deficient cells display only a partial reduction in interferon production in response to RNA virus infection and are not defective in NF-κB activation. Here we find that the related ubiquitin ligase TRAF5 is a downstream target of MAVS that mediates both IRF3 and NF-κB activation. The TM domain of MAVS allows it to dimerize and thereby associate with TRAF5 and induce its ubiquitination in a CARD-dependent manner. Also, NEMO is recruited to the dimerized MAVS CARD domain in a TRAF3 and TRAF5-dependent manner. Thus, our findings reveal a possible function for TRAF5 in mediating the activation of IRF3 and NF-κB downstream of MAVS through the recruitment of NEMO. TRAF5 may be a key molecule in the innate response against viral infection

Systematical research on the aerodynamic noise of the high-lift airfoil based on FW-H method

In numerical computation of aerodynamic noises, the solution accuracy of flow fields has an obvious impact on detailed computation of eddy turbulence and acoustic results. In this paper, LES (Large Eddy Simulation) was used to conduct numerical simulation of flow fields of three-dimensional high-lift L1T2 airfoil. Unsteady flow field data on the solid wall face was extracted as the noise source. The integration method FW-H (Ffowcs Williams-Hawkings) was used to compute far-field noises. The numerical computation method was verified by experiments. Results show that: the numerical computation method used in this paper can provide an accurate solution for computing far-field aerodynamic noises. Finally, based on the verified numerical model, contribution amounts made by each high-lift airfoil component to noises as well as major factors affecting aerodynamic noises were analyzed. Computational results show that: the leading edge slats generated aerodynamic noises mainly because of the unsteady waves which were caused by the grooves between the slat and main wing, as well as small wake eddies generated on the trailing edge of slats; flaps generated aerodynamic noises mainly because of mixing between high-frequency small-scale eddies and low-frequency large-scale eddies caused by flow separation around the wing flaps. Acoustic directivity of leading edge slats and trailing edge flaps showed an obvious dipole characteristic. For both of them, the sound pressure levels reached the maximum value in the direction perpendicular to the chord line

Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial-mesenchymal transition in mice.

Growing evidence suggests close associations between periodontitis and atherosclerosis. To further understand the pathological relationships of these associations, we developed periodontitis with ligature placement around maxillary molars or ligature placement in conjunction with Porphyromonas gingivalis lipopolysaccharide injection at the ligature sites (ligature/P.g. LPS) in Apolipoprotein E knock out mice and studied the atherogenesis process in these animals. The mice were fed with high fat diet for 11 weeks and sacrificed for analyzing periodontitis, systemic inflammation, and atherosclerosis. Controls did not develop periodontitis or systemic inflammation and had minimal lipid deposition in the aortas, but mice receiving ligature or ligature/P.g. LPS showed severe periodontitis, systemic inflammation, and aortic plaque formation. The aortic plaque contained abundant macrophages and cells expressing both endothelial and mesenchymal cell markers. The severity of periodontitis was slightly higher in mice receiving ligature/P.g. LPS than ligature alone, and the magnitude of systemic inflammation and aortic plaque formation were also notably greater in the mice with ligature/P.g. LPS. These observations indicate that the development of atherosclerosis is due to systemic inflammation caused by severe periodontitis. In vitro, P.g. LPS enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells. Moreover, secretory proteins, such as TNF-α, from macrophages induced endothelial-mesenchymal transitions of the endothelial cells. Taken together, systemic inflammation induced by severe periodontitis might exacerbate atherosclerosis via, in part, causing aberrant functions of vascular endothelial cells and the activation of macrophages in mice

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

SadTalker: Learning Realistic 3D Motion Coefficients for Stylized Audio-Driven Single Image Talking Face Animation

Generating talking head videos through a face image and a piece of speech audio still contains many challenges. ie, unnatural head movement, distorted expression, and identity modification. We argue that these issues are mainly because of learning from the coupled 2D motion fields. On the other hand, explicitly using 3D information also suffers problems of stiff expression and incoherent video. We present SadTalker, which generates 3D motion coefficients (head pose, expression) of the 3DMM from audio and implicitly modulates a novel 3D-aware face render for talking head generation. To learn the realistic motion coefficients, we explicitly model the connections between audio and different types of motion coefficients individually. Precisely, we present ExpNet to learn the accurate facial expression from audio by distilling both coefficients and 3D-rendered faces. As for the head pose, we design PoseVAE via a conditional VAE to synthesize head motion in different styles. Finally, the generated 3D motion coefficients are mapped to the unsupervised 3D keypoints space of the proposed face render, and synthesize the final video. We conduct extensive experiments to show the superior of our method in terms of motion and video quality.Comment: Project page: https://sadtalker.github.i

Algorithms for probabilistic uncertain linguistic multiple attribute group decision making based on the GRA and CRITIC method: application to location planning of electric vehicle charging stations

Electric vehicles (EVs) could be regarded as one of the most innovative and high technologies all over the world to cope with the fossil fuel energy resource crisis and environmental pollution issues. As the initiatory task of EV charging station (EVCS) construction, site selection play an important part throughout the whole life cycle, which is deemed to be multiple attribute group decision making (MAGDM) problem involving many experts and many conflicting attributes. In this paper, a grey relational analysis (GRA) method is investigated to tackle the probabilistic uncertain linguistic MAGDM in which the attribute weights are completely unknown information. Firstly, the definition of the expected value is then employed to objectively derive the attribute weights based on the CRiteria Importance Through Intercriteria Correlation (CRITIC) method. Then, the optimal alternative is chosen by calculating largest relative relational degree from the probabilistic uncertain linguistic positive ideal solution (PULPIS) which considers both the largest grey relational coefficient from the PULPIS and the smallest grey relational coefficient from the probabilistic uncertain linguistic negative ideal solution (PULNIS). Finally, a numerical case for site selection of electric vehicle charging stations (EVCS) is designed to illustrate the proposed method. The result shows the approach is simple, effective and easy to calculate

AnimateZero: Video Diffusion Models are Zero-Shot Image Animators

Large-scale text-to-video (T2V) diffusion models have great progress in recent years in terms of visual quality, motion and temporal consistency. However, the generation process is still a black box, where all attributes (e.g., appearance, motion) are learned and generated jointly without precise control ability other than rough text descriptions. Inspired by image animation which decouples the video as one specific appearance with the corresponding motion, we propose AnimateZero to unveil the pre-trained text-to-video diffusion model, i.e., AnimateDiff, and provide more precise appearance and motion control abilities for it. For appearance control, we borrow intermediate latents and their features from the text-to-image (T2I) generation for ensuring the generated first frame is equal to the given generated image. For temporal control, we replace the global temporal attention of the original T2V model with our proposed positional-corrected window attention to ensure other frames align with the first frame well. Empowered by the proposed methods, AnimateZero can successfully control the generating progress without further training. As a zero-shot image animator for given images, AnimateZero also enables multiple new applications, including interactive video generation and real image animation. The detailed experiments demonstrate the effectiveness of the proposed method in both T2V and related applications.Comment: Project Page: https://vvictoryuki.github.io/animatezero.github.io