Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been ...elucidated. Here we perform single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers. Secretome gene analysis revealed a highly connected network of intrahepatic signaling and disruption of vascular signaling in NASH. We uncovered the emergence of NASH-associated macrophages (NAMs), which are marked by high expression of triggering receptors expressed on myeloid cells 2 (Trem2), as a feature of mouse and human NASH that is linked to disease severity and highly responsive to pharmacological and dietary interventions. Finally, hepatic stellate cells (HSCs) serve as a hub of intrahepatic signaling via HSC-derived stellakines and their responsiveness to vasoactive hormones. These results provide unprecedented insights into the landscape of intercellular crosstalk and reprogramming of liver cells in health and disease.
Display omitted
•Heterogeneity and plasticity of non-parenchymal cells in healthy and NASH liver•Landscape of intrahepatic ligand-receptor signaling at single-cell resolution•Emergence of Trem2+ NASH-associated macrophages (NAMs) in mouse and human NASH•Stellakine secretion and contractile response to vasoactive hormones by HSCs
This work illustrates the heterogeneity of liver non-parenchymal cells (NPCs) and their reprogramming during NASH pathogenesis. Using single-cell RNA-sequencing analysis, the authors mapped the landscape of the intrahepatic ligand-receptor signaling network and revealed two fundamental aspects of HSC biology: stellakine secretion and contractile response to vasoactive hormones. Hepatic vascular dysfunction and emergence of Trem2+ NASH-associated macrophages (NAMs) are two conserved features of mouse and human NASH.
The proliferation of big data has brought an urgent demand for privacy-preserving data publishing. Traditional solutions to this demand have limitations on effectively balancing the trade-off between ...privacy and utility of the released data. To address this problem, the database community and machine learning community have recently studied a new problem of tabular data synthesis using generative adversarial networks (GANs) and proposed various algorithms. However, a comprehensive comparison between GAN-based methods and conventional approaches is still lacking, making it unclear why and how GANs can outperform conventional approaches in synthesizing tabular data. Moreover, it is difficult for practitioners to understand which components are necessary when building a GAN model for tabular data synthesis. To bridge this gap, we conduct a comprehensive experimental study that investigates applying GAN to tabular data synthesis. We introduce a unified GAN-based framework and define a space of design solutions for each component in the framework, including neural network architectures and training strategies. We provide optimization techniques to handle difficulties in training GAN in practice. We conduct extensive experiments to explore the design space, comparing with traditional data synthesis approaches. Through extensive experiments, we find that GAN is very promising for tabular data synthesis and provide guidance for selecting appropriate design choices. We also point out limitations of GAN and identify future research directions. We make all code and datasets public for future research.
Abstract
Etching (often considered as decomposition) is one of the key considerations in the synthesis, storage, and application of metal nanoparticles. However, the underlying chemistry of their ...etching process still remains elusive. Here, we use real-time electrospray ionization mass spectrometry to study the reaction dynamics and size/structure evolution of all the stable intermediates during the etching of water-soluble thiolate-protected gold nanoclusters (Au NCs), which reveal an unusual “recombination” process in the oxidative reaction environment after the initial decomposition process. Interestingly, the sizes of NC species grow larger and their ligand-to-metal ratios become higher during this recombination process, which are distinctly different from that observed in the reductive growth of Au NCs (e.g., lower ligand-to-metal ratios with increasing sizes). The etching chemistry revealed in this study provides molecular-level understandings on how metal nanoparticles transform under the oxidative reaction environment, providing efficient synthetic strategies for new NC species through the etching reactions.
Hepatic lipogenesis is aberrantly induced in nonalcoholic fatty liver disease (NAFLD) via activation of the LXR-SREBP1c pathway. To date, a number of protein factors impinging on the transcriptional ...activity of LXR and SREBP1c have been elucidated. However, whether this regulatory axis interfaces with long noncoding RNAs (lncRNAs) remains largely unexplored. Here we show that hepatic expression of the lncRNA Blnc1 is strongly elevated in obesity and NAFLD in mice. Blnc1 is required for the induction of SREBP1c and hepatic lipogenic genes in response to LXR activation. Liver-specific inactivation of Blnc1 abrogates high-fat diet-induced hepatic steatosis and insulin resistance and protects mice from diet-induced nonalcoholic steatohepatitis. Proteomic analysis of the Blnc1 ribonucleoprotein complex identified EDF1 as a component of the LXR transcriptional complex that acts in concert with Blnc1 to activate the lipogenic gene program. These findings illustrate a lncRNA transcriptional checkpoint that licenses excess hepatic lipogenesis to exacerbate insulin resistance and NAFLD.
Optical humidity sensors have evolved through decades of research and development, constantly adapting to new demands and challenges. The continuous growth is supported by the emergence of a variety ...of optical fibers and functional materials, in addition to the adaptation of different sensing mechanisms and optical techniques. This review attempts to cover the majority of optical humidity sensors reported to date, highlight trends in design and performance, and discuss the challenges of different applications.
Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders ...adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
In this paper, the design and underpinning technical principles of the novel design of a negative pressure wave (NPW)-based pipeline leak detection system has been reported, which is configured using ...fiber Bragg grating (FBG) pressure sensors. To evaluate this, a pipeline leakage test platform has been established and experiments have been conducted, to verify the performance of a system using this FBG-based approach. The results show that a system using FBG-based sensors can accurately determine the pressure change trends along the pipeline and thus allow the calculation of the NPW velocity online. A key comparison is made with traditional NPW detection techniques, showing that the novel detection system is capable of achieving the higher leak-location accuracy and the detection of smaller leakage volumes. This arises from the ability of the FBG-based system to allow an increased number of sensors to be multiplexed along the pipeline. Their corresponding output signals generated show a very satisfactory, high signal-to-noise ratio. The system has been evaluated, especially in its response to extraneous signals and thus disturbances caused by the pump starting or stopping can be eliminated. This was achieved through an analysis of the time sequence of the pressure changes captured by the multisensor array being carried out and thus immunity to such effects demonstrated. The system has thus been designed to minimize the instances where a false alarm occurs.
Background and Aims
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease that is characterized by liver injury, inflammation, and fibrosis. NASH pathogenesis is linked to reprogramming ...of chromatin landscape in the liver that predisposes hepatocytes to stress‐induced tissue injury. However, the molecular nature of the putative checkpoint that maintains chromatin architecture and preserves hepatocyte health remains elusive.
Approach and Results
Here we show that heterogeneous nuclear ribonucleoprotein U (hnRNPU), a nuclear matrix protein that governs chromatin architecture and gene transcription, is a critical factor that couples chromatin disruption to NASH pathogenesis. RNA‐seq and chromatin immunoprecipitation‐seq studies revealed an extensive overlap between hnRNPU occupancy and altered gene expression during NASH. Hepatocyte‐specific inactivation of hnRNPU disrupted liver chromatin accessibility, activated molecular signature of NASH, and sensitized mice to diet‐induced NASH pathogenesis. Mechanistically, hnRNPU deficiency stimulated the expression of a truncated isoform of TrkB (TRKB‐T1) that promotes inflammatory signaling in hepatocytes and stress‐induced cell death. Brain‐derived neurotrophic factor treatment reduced membrane TRKB‐T1 protein and protected mice from diet‐induced NASH.
Conclusions
These findings illustrate a mechanism through which disruptions of chromatin architecture drive the emergence of disease‐specific signaling patterns that promote liver injury and exacerbate NASH pathogenesis.
In this study, the CsPbBrI2 perovskite film was prepared by the preparation of the sol-gel and the spin-coating method, and the cubic lattice was stabilized by introducing Br+ into the CsPbI3 film, ...which solved the problem of instability of the traditional perovskite phase. Based on the CsPbBrI2 perovskite film, the Ag/CsPbBrI2/ITO memory device with a resistance switching effect was prepared. The morphology and phase compositions of the film were analyzed by scanning electron microscope and X-ray diffraction. The non-volatile and repeatable resistance switching effect of the Ag/CsPbBrI2/ITO memory device was measured under open-air conditions. The experimental results show that the surface of the CsPbBrI2 perovskite film is uniform and dense, and the Ag/CsPbBrI2/ITO memory device has an order of magnitude resistance-on-off ratio after 500 cycles of cyclic voltage. This study shows that Ag/CsPbBrI2/ITO memory devices based on CsPbBrI2 perovskite films have potential applications in the field of non-volatile memory devices. At the same time, the transient properties of the CsPbBrI2 film that can quickly dissolve in deionized water make it potentially useful in short-period data storage units and implantable electronic devices with human or environmental sensors.
PDF
