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Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells. The activation of cGAS, in turn, triggers the production of SASP factors via stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS–STING pathway in vitro and we show cGAS-dependent regulation of senescence following irradiation and oncogene activation in vivo . Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS–STING pathway as a crucial regulator of senescence and the SASP. Glück et al. find that the DNA-sensing component cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments produced in senescent cells leading to STING-mediated production of SASPs, which promotes paracrine senescence.

Senescence, a persistent form of cell-cycle arrest, is often associated with a diverse secretome, which provides complex functionality for senescent cells within the tissue microenvironment. We show that oncogene-induced senescence is accompanied by a dynamic fluctuation of NOTCH1 activity, which drives a TGF-β-rich secretome, while suppressing the senescence-associated pro-inflammatory secretome through inhibition of C/EBPβ. NOTCH1 and NOTCH1-driven TGF-β contribute to ‘lateral induction of senescence’ through a juxtacrine NOTCH–JAG1 pathway. In addition, NOTCH1 inhibition during senescence facilitates upregulation of pro-inflammatory cytokines, promoting lymphocyte recruitment and senescence surveillance in vivo . As enforced activation of NOTCH1 signalling confers a near mutually exclusive secretory profile compared with typical senescence, our data collectively indicate that the dynamic alteration of NOTCH1 activity during senescence dictates a functional balance between these two distinct secretomes: one representing TGF-β and the other pro-inflammatory cytokines, highlighting that NOTCH1 is a temporospatial controller of secretome composition. Hoare et al.  find that NOTCH1 regulates the switch between two distinct senescence-associated secretomes—the TGF-β pathway and pro-inflammatory cytokines—and that its inhibition promotes clearance of oncogene-induced senescent liver cells.

Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans. Together, our results provide insight into lineage commitment in liver tumorigenesis, and explain molecularly why common liver-damaging risk factors can lead to either HCC or ICC. The tumour microenvironment determines which type of liver cancer develops, with transformed hepatocytes giving rise to intrahepatic cholangiocarcinoma or hepatocellular carcinoma depending or whether they are surrounded by cells undergoing necroptosis or apoptosis.

Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo . Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15 INK4b and p21 CIP1 . Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo . A property of oncogene-induced senescence (OIS) is the induction of a secretory phenotype, termed the senescence-associated secretome (SASP). Gil and colleagues now provide evidence that senescence can be transmitted in a paracrine manner, by showing that induction of the SASP in cells undergoing OIS by inflammasome-mediated interleukin-1 signalling can promote senescence of normal neighbouring cells.

This paper proposes a post-processing method called bidirectional interpolation method for sampling-based path planning algorithms, such as rapidly-exploring random tree (RRT). The proposed algorithm applies interpolation to the path generated by the sampling-based path planning algorithm. In this study, the proposed algorithm is applied to the path created by RRT-connect and six environmental maps were used for the verification. It was visually and quantitatively confirmed that, in all maps, not only path lengths but also the piecewise linear shape were decreased compared to the path generated by RRT-connect. To check the proposed algorithm’s performance, visibility graph, RRT-connect algorithm, Triangular-RRT-connect algorithm and post triangular processing of midpoint interpolation (PTPMI) were compared in various environmental maps through simulation. Based on these experimental results, the proposed algorithm shows similar planning time but shorter path length than previous RRT-like algorithms as well as RRT-like algorithms with PTPMI having a similar number of samples.

This study aims to analyze the effects of dynamic motion and structural response of semi-submersible floating offshore wind turbine structures (FOWTs) in waves generated in hurricane environments. The extreme environment utilizes numerical simulation data of hurricanes and is divided into low-frequency and high-frequency components based on wave-age, and a load case combining wind and wave is applied. As the hurricane progresses, a spectrum divided into swell and wind sea components is generated in the ocean, and the swell component is distributed in the natural frequency range of the structure, increasing the dynamic response. Dynamic analysis compares the cumulative response by fitting the response for each wave component generated by the hurricane through the Gaussian mixture model. In the structural analysis, the hydrodynamic pressure calculated through diffraction analysis is mapped to a finite element model using the quasi-dynamics interaction method, and the von Mises stress per wave component is analyzed. Through this, it is possible to grasp the main factors of the dynamic and structural responses of semi-submersible FOWTs.

The ongoing expansion of the Fourth Industrial Revolution has led to a diversification of drone applications. Among them, this paper focuses on the critical technology required for load management using drones. Generally, when using autonomous drones, global positioning system (GPS) receivers attached to the drones are used to determine the drone’s position. However, GPS integrated into commercially available drones have an error margin on the order of several meters. This paper, proposes a method that uses fixed-size quick response (QR) codes to maintain the error of drone 3D localization within a specific range and enable accurate mapping. In the drone’s 3D localization experiment, the errors were maintained within a specific range, with average errors ranging from approximately 0 to 3 cm, showing minimal differences. During the mapping experiment, the average error between the actual and estimated positions of the QR codes was consistently around 0 to 3 cm.

The multiple mechanisms of entrepreneurial intention are still an open issue, and few have explored whether the relationship between entrepreneurial intention and proactive personality is influenced by entrepreneurial passion. This study aims to reveal the mediation role of entrepreneurial passion between proactive personality and entrepreneurial intention with the application of the classic structural equation modeling. A questionnaire survey was conducted on Chinese undergraduates and 647 questionnaires were collected for the further analysis. The main findings shed light on the mechanisms that underpin entrepreneurial passion and contribute to the growing body of knowledge on entrepreneurial intention and will raise implications for both academic entrepreneurial theory and practice.

Environment maps must first be generated to drive mobile robots automatically. Path planning is performed based on the information given in an environment map. Various types of sensors, such as ultrasonic and laser sensors, are used by mobile robots to acquire data on its surrounding environment. Among these, the laser sensor, which has the property of being able to go straight and high accuracy, is used most often. However, the beams from laser sensors are refracted and reflected when it meets a transparent obstacle, thus generating noise. Therefore, in this paper, a state-of-the-art algorithm was proposed to detect transparent obstacles by analyzing the pattern of the reflected noise generated when a laser meets a transparent obstacle. The experiment was carried out using the environment map generated by the aforementioned method and gave results demonstrating that the robot could avoid transparent obstacles while it was moving towards the destination.

Significance Solids have been mainly studied at ambient conditions (i.e., at room temperature and zero pressure). However, it was realized early that there is also a fundamental relation between volume and structure and that this dependence could be most fruitfully studied by means of high-pressure experimental techniques. From a theoretical point of view this is an ideal type of experiment, because only the volume is changed, which is a very clean variation of the external conditions. In the present study we show a hard superconducting material, iron tetraboride, transforms into a novel transparent phase under pressure. Further, this phase is the first system in this class, to our knowledge, and opens a new route to search for and design new transparent materials. First principles–based electronic structure calculations of superhard iron tetraboride (FeB ₄) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure acts as a demarcation between two distinct crystal symmetries, metallic orthorhombic and semiconducting tetragonal phases, with Pnnm and I 4 ₁/ acd space groups, respectively. In this work, the electron–phonon coupling-derived superconducting T c has been determined up to 60 GPa and along with optical band gap variation with increasing pressure up to 300 GPa. The dynamic stability has been confirmed by phonon dispersion calculations throughout this study.