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STING-dependent cytosolic DNA sensing in dendritic cells (DCs) initiates antitumor immune responses, but how STING signaling is metabolically regulated in the tumor microenvironment remains unknown. Here, we show that oxidative stress is required for STING-induced DC antitumor function through a process that directs SUMO-specific protease 3 (SENP3) activity. DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon (IFN) signaling in DCs and dampening antitumor immune responses. DC-derived reactive oxygen species (ROS) trigger SENP3 accumulation and the SENP3-IFI204 interaction, thereby catalyzing IFI204 deSUMOylation and boosting STING signaling activation in mice. Consistently, SENP3 senses ROS to facilitate STING-dependent DC activity in tissue samples from colorectal cancer patients. Our results reveal that oxidative stress as a metabolic regulator promotes STING-mediated DC antitumor immune responses and highlights SENP3 as an overflow valve for STING signaling induction in the metabolically abnormal tumor microenvironment.

Moxifloxacin (MFX) shows goodA formulation ofSignificantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference.MFX showed limited efficacy against

Metabolic programs are crucial for T reg cell stability and function. Yu et al. report that TRAF3IP3 acts as a pivotal regulator in controlling metabolic fitness to maintain T reg cell stability and function at the lysosome., Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg–specific deletion of Traf3ip3 impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)–mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells. Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our results define TRAF3IP3 as a metabolic regulator in T reg cell stability and function and suggest a lysosome-specific mTORC1 signaling mechanism that regulates T reg cell metabolism., Graphical Abstract

Numerical moment matching (NMM) technique is a point estimation method that holds significant applicability in the era of large-scale data. One can use NMM to create an extremely small set of representative samples of an engineering population or to facilitate a fast and robust uncertainty quantification of a complex structure. However, the previous NMM method based on the multivariate Newton-Raphson (mNR) scheme often suffers from severe numerical divergence and initial-value dependency. This study overcomes the aforementioned limitations by stabilizing NMM with a genetic algorithm (GA), giving rise to a highly stable and fast NMM (denoted as GA-NMM). Inheriting NMM’s strengths, GA-NMM exhibits no restriction to irregular distributions, large sizes, or many variables of engineering data. This paper elaborates the formulations of GA-NMM along with a practical recommendation for setting optimal parameters. Validations encompass theoretical and practical cases. Simulations with the default setting of GA-NMM demonstrate successful performances in data-squashing of an engineering population and a fast, robust uncertainty quantification of a complex structure. All the developed programs are made publicly available for promoting data-driven research paradigm in broader engineering domains.

For seeking a lightweight thermochromic film acting as a smart radiation device in thermal control system for spacecraft, the (La,Ca,K)MnO3±δ films with different thicknesses were deposited on Si(100) substrate by magnetron sputtering method with a target which was synthesized by a sol-gel method. The crystal structure and micro-morphology of these films are investigated. The results reveal that all films form an orthorhombic perovskite structure, and it undergoes a Volmer-Weber growth mode with the increased thickness. Temperature-dependent infrared reflectivity and emittance are investigated. Spectra data indicate that reflectivity of all films has a decreased trend with increasing temperature. In the temperature range of 173–373 K, the K-doped thermochromic films show a large emittance increment near 0.36 with film thickness only 321 nm. All of these results show that the thermochromic film has a great potential to be applied to a more lightweight and cost-effective thermal control device in spacecraft with an excellent radiation performance.

The technology of human detection is evolving rapidly and it has been applied in various fields. Histograms of oriented gradients (HOG) are proven to be able to significantly outperform existing feature sets for human detection. This paper presents a foreground-based scalloped (FSR)-HOG features with rotation invariance for human detection. Firstly, extracting the FSRHOG human features on the foreground image, then training the positive and negative samples by SVM linear classifier. Experimental results show that the FSRHOG feature vector can retain the accuracy of HOG as well as improve the detection rate, and it is suitable for human detection with high motion complexity.

Objective To investigate the mechanism of dexmedetomidine (Dex) in improving brain damage induced by cerebral ischemia-reperfusion injury in rats. Methods Rats were randomly divided into a sham operation group, ischemia-reperfusion group, Dex group, piracetam group, and yohimbine + Dex group, with 12 rats per group. 2,3,5-Triphenyltetrazolium chloride staining was used to analyze cerebral infarct size. Hematoxylin-eosin staining and immunohistochemistry were used to observe brain damage caused by ischemia-reperfusion. Cognitive and memory functions was detected by Morris water maze test, and the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (CREB) were measured by Western blot. Results Cognitive dysfunction was improved in the Dex group and the piracetam group compared with the ischemia-reperfusion group. Compared with the ischemia-reperfusion group, infarct size and neuronal cell death rates were decreased in the Dex group and the piracetam group. The expression of phosphorylated ERK1/2 and phosphorylated CREB in the Dex group was increased, whereas the expression of phosphorylated ERK1/2 and phosphorylated CREB in the yohimbine + Dex group was lower than in the Dex group (P Conclusions Dex improved ischemic brain damage by promoting signal transduction of the ERK/CREB pathway, which may provide new ways for clinical treatment of cerebral ischemia-reperfusion injury.

We tend to think that perceptual experiences tell us about what the external world is like without being influenced by our own mind. But recent psychological and philosophical research indicates that this might not be true. Our beliefs, expectations, knowledge, and other personal-level mental states might influence what we experience. This kind of psychological phenomena is now called “cognitive penetration.” The research of cognitive penetration not only has important consequences for psychology and the philosophy of mind, but also has interesting epistemological implications. According to the Downgrade Thesis, some cognitively penetrated perceptual experiences give their subjects less justification for believing their penetrated contents than perceptual experiences that are unpenetrated to represent those contents would usually give. In this paper, I propose an innovative argument for the Downgrade Thesis. First, I develop a positive account of how some cognitive penetration works, according to which cognitive states influence perceptual experiences by triggering some imaginings. Second, I argue that imaginings do not give their subjects justification for believing their contents. I apply this epistemology of imagining to cognitive penetration, and argue that because of the role that imaginings play, some cognitively penetrated experiences also give their subjects less justification for believing their penetrated contents.

Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4+ T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance., Regulatory T cells are crucial for the establishment and maintenance of peripheral immune tolerance, yet the mechanisms regulating their stability and function remain to be fully elucidated. Here the authors show SENP3 maintains Treg cell stability and function via BACH2 deSUMOylation.

To investigate effect of miR-145 on learning and memory ability in rats with epilepsy.Rats with epilepsy were induced by lithium chloride-pilocarpine. miR-145 antagomir and antagomir-control were injected into epileptic brains by the stereotactic technique, respectively. Then, rats were divided into a normal group (N), epilepsy group (Ep), miR-145 antagomir group (A) and antagomir-control group (C). After 1 and 7 days of treatment, the expression of miR-145 and Caspase-9 were detected, and the apoptosis of hippocampal neurons in CA1 of hippocampus was detected. After 7 days of treatment, the learning and memory abilities of rats was measured by using the Morris water maze test.The rat epilepsy model was successfully constructed. Compared with the N group, the target quadrant time and platform crossing times were reduced and the expression of miR-145 and Caspase-9 was increased in the epilepsy groups (P0.05). Compared with the Ep and C groups, the target quadrant time and platform crossing times were increased and the expression of miR-145 and Caspase-9 was down-regulated in the A group (P0.05). The number of apoptotic hippocampal neurons in the hippocampal CAl area of the Ep group was more than that in the N group and in the A group was less than that in the C group at 1 and 7 days after modeling respectively (P0.05).Down-regulated miR-145 improved the apoptosis of hippocampal neurons by reducing the Caspase-9 expression in hippocampus and further affected learning and memory abilities of rats with epilepsy.

The LBP histogram obtained based on the local binary pattern (LBP) method usually has a higher dimension, and not conducive to calculation. The LBP method adopts the gray difference value between single points as the LBP output value, which is not robust to noise and illumination. Therefore, this paper improves the traditional LBP method and proposes a surface defect detection method based on gradient local binary pattern (GLBP), which uses image sub-blocks to reduce the dimensionality of the LBP data matrix. The method adopts weighted binary output values in eight directions within the neighborhood to indicate local gray changes, which suppresses the effects of light and noise on the detection results. Experiments show that the method can determine the defect location well and provide good feature information for subsequent defect classification.

Understanding the synergy between metal and zeolite for catalytic aquathermolysis harbours tremendous scientific and industrial importance. Herein, HZSM-5 is used as a model zeolite due to uniform physico-chemical structure, which is required to elucidate the intrinsic structure-performance relationship. We first devise a novel and scalable strategy to synthesize recyclable magnetic Fe3O4/HZSM-5 catalyst, which shows enhanced catalytic aquathermolysis performance compared to pure HZSM-5 catalyst. Moreover, the underlying synergy effect is then systematically elucidated by multi-techniques such as 1H NMR, HRTEM, Py-IR, NH3-TPD, SARA and EL. Importantly, it is found that the change of acidity is not the dominating reason for enhanced performance. The synergy not only favors dispersion of Fe3O4 nanoparticles on zeolite, but also effectively breaks CS bond and reduces the percentages of resin and asphaltene. Furthermore, the designed Fe3O4/zeolite catalyst effectively reduces the viscosity of heavy crude oil by 85.0%. This work sheds new light on the design of highly efficient heterogeneous catalysts for catalytic aquathermolysis.