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Stimulator of interferons genes (STING), which is crucial for the secretion of type I interferons and proinflammatory cytokines in response to cytosolic nucleic acids, plays a key role in the innate immune system. Studies have revealed the participation of the STING pathway in unregulated inflammatory processes, traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid haemorrhage (SAH) and hypoxic–ischaemic encephalopathy (HIE). STING signalling is markedly increased in CNS injury, and STING agonists might facilitate the pathogenesis of CNS injury. However, the effects of STING-regulated signalling activation in CNS injury are not well understood. Aberrant activation of STING increases inflammatory events, type I interferon responses, and cell death. cGAS is the primary pathway that induces STING activation. Herein, we provide a comprehensive review of the latest findings related to STING signalling and the cGAS–STING pathway and highlight the control mechanisms and their functions in CNS injury. Furthermore, we summarize and explore the most recent advances toward obtaining an understanding of the involvement of STING signalling in programmed cell death (autophagy, necroptosis, ferroptosis and pyroptosis) during CNS injury. We also review potential therapeutic agents that are capable of regulating the cGAS–STING signalling pathway, which facilitates our understanding of cGAS–STING signalling functions in CNS injury and the potential value of this signalling pathway as a treatment target.

Pore‐fluid pressure (PP) plays an important role in bed erosion, but the mechanisms that control PP evolution and the resulting feedbacks on flow dynamics are unclear. Here, we develop a general formulation, allowing quantification of the propensity for PP evolution of saturated and unsaturated bed sediments. We conduct erosion experiments by systematically varying grain composition and water content of beds, for investigating effects of PP evolution on flow erosion. With increasing water content, PP shows a slight rise in deforming beds with drained behavior but significant larger rise in undrained beds. Regardless of bed composition, the erosion rate of beds presents a synchronous change tendency with PP evolution due to the loss in basal friction. PP instigates positive feedback that induces a remarkable gain of flow velocity and momentum on wet beds with undrained behavior. Our results help explain observations of volume growth and long run out of debris flows. Plain Language Summary Debris flows are common geophysical flows consisting of debris grains and muddy water. Debris flows can grow significantly in volume and mobility as they pick up loose sediment from gully bed and banks. The destructive potential of debris flows increases with increasing flow volume and run out. This brings about great challenges for effective early warning of debris flows, design of prevention measures and mapping of hazard zones related to human settlements. It is commonly believed that flow momentum is consumed by carrying static bed sediments. However, flows can gain momentum by overriding wet bed sediments. This can be explained by pore‐pressure generation as debris flows move across wet beds. The increase of measured pore‐fluid pressure is limited for beds with a low water content, but substantial for beds with a higher water content, which strongly affects the erosion rates of bed sediments. Flow velocity and momentum on wet beds are observed to increase significantly but slightly for dryer beds as a result of the pore‐pressure feedback. These findings indicate that the debris composition of the catchment, the water content of bed sediment and the pore‐pressure development should be evaluated when making predictions on debris‐flow hazard. Key Points Propensity for pore pressure evolution of bed sediments during debris‐flow erosion is evaluated by a Deborah number Significant pore pressure and accompanying intense erosion occur for wet bed sediments with undrained behavior Enhanced pore pressure of wet bed sediments reduces flow basal friction, increasing flow mobility and runout

Myocardial injury induced by ischemia-reperfusion or doxorubicin leads to cardiomyocyte necroptosis via RIP3-mediated phosphorylation of CaMKII and opening of the mitochondrial permeability transition pore. Regulated necrosis (necroptosis) and apoptosis are crucially involved in severe cardiac pathological conditions, including myocardial infarction, ischemia-reperfusion injury and heart failure. Whereas apoptotic signaling is well defined, the mechanisms that underlie cardiomyocyte necroptosis remain elusive. Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca 2+ -calmodulin–dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL. In mice, RIP3 deficiency or CaMKII inhibition ameliorates myocardial necroptosis and heart failure induced by ischemia-reperfusion or by doxorubicin treatment. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. These findings identify CaMKII as a new RIP3 substrate and delineate a RIP3-CaMKII-mPTP myocardial necroptosis pathway, a promising target for the treatment of ischemia- and oxidative stress–induced myocardial damage and heart failure.

Examines the effectiveness of information technology in reducing corruption in China. Proposes an electronic monitoring system (EMS) in five cities, then designs a model of e-government system success to evaluate the EMS. Explores whether EMS can be evaluated in terms of the DeLone and McLean information systems (IS) success model. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

The impairment of mitochondrial bioenergetics, often coupled with exaggerated reactive oxygen species (ROS) production, is a fundamental disease mechanism in organs with a high demand for energy, including the heart. Building a more robust and safer cellular powerhouse holds the promise for protecting these organs in stressful conditions. Here, we demonstrate that NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1), also known as mitochondrial acyl carrier protein, acts as a powerful cardio-protector by conferring greater capacity and efficiency of mitochondrial energy metabolism. In particular, NDUFAB1 not only serves as a complex I subunit, but also coordinates the assembly of respiratory complexes I, II, and III, and supercomplexes, through regulating iron-sulfur biosynthesis and complex I subunit stability. Cardiac-specific deletion of Ndufab1 in mice caused defective bioenergetics and elevated ROS levels, leading to progressive dilated cardiomyopathy and eventual heart failure and sudden death. Overexpression of Ndufab1 effectively enhanced mitochondrial bioenergetics while limiting ROS production and protected the heart against ischemia-reperfusion injury. Together, our findings identify that NDUFAB1 is a crucial regulator of mitochondrial energy and ROS metabolism through coordinating the assembly of respiratory complexes and supercomplexes, and thus provide a potential therapeutic target for the prevention and treatment of heart failure.

Urban environments have a strong influence on the land surface temperature (LST) in urban areas. Understanding the relationship between LST and urban environmental factors can help develop effective strategies to reduce high LSTs in urban areas, which is critical for mitigating the urban heat island effect. Previous studies have focused on the correlation between LST and the environmental factors that drive its formation, without considering the influences of the neighboring environment and the vertical expansion of highly urbanized areas. Notably, the correlation between LST and its neighboring environment in different seasons remains unclear. In this study, we selected central Beijing in China as our study area and employed the moving window method to characterize the environmental factors of the neighboring environment of the central LST cell. We explored eight environmental factors from three layers: normalized difference vegetation index (NDVI), normalized difference built-up index (NDBI), modified normalized difference water index (MNDWI), building density (BD), building height (BH), building volume (BV), sky view factor (SVF), and road density (RD). The Pearson correlation and extreme gradient boosting (XGB) regression methods were applied to measure the correlation between LST and the different factors in moving windows of different sizes. The results indicated that the correlation between NDVI, MNDWI, and LST was considerably different in the winter and other seasons. However, NDBI was positively correlated with LST in all seasons, although the correlation was strongest/weakest in summer/winter. Among building-related factors, BD and BH were more strongly correlated with LST, and the positive/negative correlation between BD/BH and LST was stronger in summer/winter. The correlation between LST and its neighboring environment varied with increasing window size, and this variation differs significantly between winter and other seasons. In spring, summer, and autumn, the strength of the correlation between LST and its neighboring environment showed an “inverted V” pattern with increasing window size. The optimal spatial scales to explore the influence of neighboring environments on the LST of 30-m cells were 210 m and 270 m. This study revealed the seasonal correlation between LST and its neighboring environment while explaining the variation at a spatial scale. Notably, this study can provide a new perspective for understanding the driving mechanism of the urban thermal environment, while contributing to its scientific optimization and management.

Debris flows can erode mountainsides, cover alluvial fans, and bury people and property by rapid deposition. The deposition characteristics of debris flows are strongly affected by their dynamics and composition, which depend on upstream sediment erosion, but how is still under scientific debate. Here, we conduct a series of experiments to analyze the effects of debris flow grain‐size gradation and eroded bed sediment on deposition characteristics. Debris flows deposit on a gentle runout zone and form coarse‐grained lateral levees and front lobes and a finer‐grained channelized interior due to grain segregation. We show that affected by a high basal pore‐fluid pressure, released mud‐sand‐gravel flows present much flatter deposits than sand‐gravel flows. Runout distance, width and inundated area increase with higher bed water content due to the growths of flow volume and momentum. Inundated area correlates to deposition volume with a power relation for all experiments. Savage number shows the greatest positive correlation with runout and inundated area among all factors, suggesting that potential energy of debris flow is more strongly consumed by grain collision stress than by basal friction stress. Debris flows can deposit as a single nose or multiple fingers depending on the relative magnitude between the friction force at the flow front balanced by downslope gravity and the thrust force of the following channelized flow with a higher speed. Our results facilitate the mapping of debris‐flow impact zones and provide a mechanistic model for predicting deposit shape in debris flows and other geophysical flows like pyroclastic flows.

Time series of vegetation indices can be utilized to capture crop phenology information, and have been widely used in land cover and crop classification, phenological feature extraction, and planting structure monitoring. This is of great significance for guiding agricultural production and formulating agricultural policies. According to the characteristics of the GF-6 satellite’s newly-added red edge bands, wide field view and high-frequency imaging, the time series of vegetation indices about multi-temporal GF-6 WFV data are used for the study of land cover and crop classification. In this study, eight time steps of GF-6 WFV data were selected from March to October 2019 in Hengshui City. The normalized difference vegetation index (NDVI) time series and 10 different red edge spectral indices time series were constructed. Then, based on principal component analysis (PCA), using two feature selection and evaluation methods, stepwise discriminant analysis (SDA) and random forest (RF), the red edge vegetation index of normalized difference red edge (NDRE) was selected. Seven different lengths of NDVI, NDRE and NDVI&NDRE time series were reconstructed by the Savizky-Golay (S-G) smoothing algorithm. Finally, an RF classification algorithm was used to analyze the influence of time series length and red edge indices features on land cover and crop classification, and the planting structure and distribution of crops in the study area were obtained. The results show that: (1) Compared with the NDRE red edge time series, the NDVI time series is more conducive to the improvement of the overall classification accuracy of crops, and NDRE can assist NDVI in improving the crop classification accuracy; (2) With the shortening of NDVI and NDRE time series, the accuracy of crop classification is gradually decreased, and the decline is gradually accelerated; and (3) Through the combination of the NDVI and NDRE time series, the accuracy of crop classification with different time series lengths can be improved compared with the single NDVI time series, which is conducive to improving the classification accuracy and timeliness of crops. This study has fully tapped the application potential of the new red edge bands of GF-6 WFV time series data, which can provide references for crop identification and classification of time series data such as NDVI and red edge vegetation index of different lengths. At the same time, it promotes the application of optical satellite data with red edge bands in the field of agricultural remote sensing.

The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2-cell (2C)-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2C-stage embryos. By studying the transition of ESCs into 2C-like cells, we identified developmental pluripotency associated 2 and 4 (Dppa2/4) as important regulators controlling zygotic transcriptional program through directly up-regulating the expression of double homeobox (Dux). In addition, we found that DPPA2 protein is sumoylated and its activity is negatively regulated by small ubiquitin-like modifier (Sumo) E3 ligase protein inhibitor of activated STAT 4 (PIAS4). PIAS4 is down-regulated during ZGA process and during transitioning of ESCs into 2C-like cells. Depleting Pias4 or overexpressing Dppa2/4 is sufficient to activate 2C-like transcriptional program, whereas depleting Dppa2/4 or forced expression of Pias4 or Sumo2-Dppa2 inhibits 2C-like transcriptional program. Furthermore, ectopic expression of Pias4 or Sumo2-Dppa2 impairs early mouse embryo development. In summary, our study identifies key molecular rivals consisting of transcription factors and a Sumo2 E3 ligase that regulate zygotic transcriptional program upstream of Dux.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPβ signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases. Dusp6, an ERK specific phosphatase, was identified as a regenerative repressor during zebrafish heart regeneration. Here, the authors show that Dusp6 deficiency improves post infarctional cardiac repair by predominantly attenuating neutrophil-mediated myocardial damage in mammalian hearts.