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A STAT gene from Scylla paramamosain , named SpSTAT , was cloned and characterized. The full length of SpSTAT mRNA contains a 5′untranslated region (UTR) of 238 bp, an open reading frame (ORF) of 2388 bp and a 3′ UTR of 326 bp. The Sp STAT protein contains four characteristic STAT domains and showed 84% identity (90% similarity) and 44% identity (64% similarity) to Litopenaeus vannamei STAT protein and Human STAT5a/b protein, respectively. The mRNA of SpSTAT was high expressed in the intestine and eyestalk and low expressed in the heart and muscle. Moreover, expression of SpSTAT was significantly responsive to challenge of mud crab reovirus (MCRV), Poly(I:C), LPS and Staphylococcus aureus. Sp STAT could be activated by Poly(I:C) and LPS to translocate to the nucleus of Drosophila Schneider 2 (S2) cells. Sp STAT could be phosphorylated by interaction with JAK of S. paramamosain (Sp JAK) and activated to translocate to the nucleus of S2 cells. Furthermore, Silencing of SpSTAT in vivo resulted in higher mortality rate of MCRV infected mud crab and increased the viral load in tissues, suggesting that SpSTAT could play an important role in defense against MCRV in mud crab. • The full length of Scylla paramamosain STAT (SpSTAT) was cloned and characterized. • SpSTAT was significantly upregulated by mud crab reovirus(MCRV), Poly(I:C) and LPS. • Sp STAT could be phosphorylated by interaction with Sp JAK in S2 cells. • The nuclear shift of Sp STAT was observed by challenge of Poly(I:C), LPS and Sp JAK. • SpSTAT could play an important role in defense against MCRV in mud crab. [ABSTRACT FROM AUTHOR]

To circumvent the limitations associated with sandwich ELISA for tissue biomarker quantitation, Quantitative Dot Blot method (QDB) was proposed using antibodies clinically validated for immunohistochemistry (IHC), as this method requires only one primary antibody in the analysis. The protein levels of four breast cancer tissue biomarkers, including Estrogen Receptor (ER), Progesterone Receptor (PR), Ki67 and Her2, were absolutely quantitated successfully in 190 frozen breast tissue biopsies, and the results were further verified with provided IHC results. We propose QDB method as an alternative platform to Sandwich ELISA for absolute quantitation of tissue biomarkers with significantly reduced developing effort and time. • QDB as alternative immunoassay platform for cellular and tissue proteins. • QDB-based assay measures tissue biomarkers absolutely and quantitatively. • An ELISA-like assay with significantly reduced developing time and effort. • Only one primary antibody in QDB compared with two in ELISA. • Using clinically validated IHC antibodies (IVD/ASR) directly in QDB. • Suitable with both native and denatured samples. [ABSTRACT FROM AUTHOR]

The currently available techniques for transferring exogenous genes into macrophages, especially the targeted import of exogenous genes into Kupffer cells (KCs) in vivo, are inefficient and achieve only low targeting. Novel Large-Pore Mesoporous Silica Nanospheres (LPMSNs) may be a promising gene transfection agent for KCs because of their superior biodegradation and hypotoxic characteristics, as well as their ability to retain the biological function of KCs and the high loading-rate of exogenous plasmid. LPMSNs were able to completely adsorb shRNA-TRAF3 (tumor necrosis factor receptor-associated factor-3) plasmid at a mass ratio as low as 30:1, and exhibited a low cytotoxicity for KCs. LPMSNs were detected in KC cytoplasm in vitro, and transmission electron microscopy (TEM) revealed that they were present only in KCs in liver tissue in vivo. The max KC transfection efficiency with LPMSNs was 34.8± 0.07%, as evaluated using flow cytometry, and the protein and mRNA levels of TRAF3 were significantly inhibited (P < 0.05) by shRNA-TRAF3 plasmid transfection after 24 h in vitro and 48 h in vivo. In conclusion, KC targeted transfection was achieved successfully by LPMSNs carrying shRNA-TRAF3 plasmids in vitro and vivo. The protein and mRNA levels of TRAF3 were suppressed significantly. These results suggest that LPMSNs are a promising vehicle for delivering exogenous genes into KCs in vitro and vivo. [ABSTRACT FROM AUTHOR]

The formed bionic "Fe/Mo bimetallene" can effectively promote the separation and transfer of photo-generated carriers by multi-electron redox reactions. [Display omitted] The "FeMo cofactors" in biological nitrogenase play a decisive role in nitrogen reduction. Herein, a novel bionic Fe/Mo bimetallene was applied in photocatalytic nitrogen reduction. The surface coating Fe/Mo bimetallene of Bi 2 Mo 0.3 W 0.7 O 6 (BMWO) nanocrystals could effectively promote the separation and transportation of photogenerated carriers by multi–electron redox reactions and deliver 2.8 times longer photo–carrier lifetime. Consequently, the nitrogen fixation activity of Fe/Mo bimetallene–coated BMWO nanocrystal photocatalyst was obviously enhanced (218.93 μmol g–1h−1), which was about 4.8 times that of unmodified BMWO nanocrystals. This work provides a novel approach to design bionic Fe/Mo bimetallene–modified inorganic semiconductor photocatalysts for nitrogen reduction. [ABSTRACT FROM AUTHOR]

A good understanding of the power system resilience is necessary for optimizing the investment strategies and supporting the emergency rescue, but the existing quantitative estimation results based on real outage events are still lacked due to the data limitations. Therefore, this study first establishes a unified framework to measure the power system resilience under different natural disasters, by integrating the electricity performance curve with the dynamic inoperability input-output model. Then, a database of 285 Chinese historical big power outage events caused by natural disasters is established, and the city-level power system resilience values are estimated. Finally, a benefit analysis is conducted for improving the power system resilience. Our major findings are that: (1) Electricity system recoveries quickest from hail (23.05 h), while restores slowest from snowstorm (117.31 h). (2) China's city electricity system is the most resilient to the thunderstorm, while is the least resilient to the earthquake. (3) Enhancing the power system resilience will significantly reduce the requirements for rescue resources, and the saved emergency rescue cost ranges from 0.57 million yuan to 12.08 million yuan with 1% reduction of initial inoperability. • Power system resilience under natural disasters is estimated • A database of disaster induced power outages is established • The sectoral interdependency is considered in the resilience estimation • The cost-benefit analysis is conducted for the resilience enhancement • Statistical analysis of the historical outage events is conducted [ABSTRACT FROM AUTHOR]

In recent years, the strategy for tumor therapy has changed from focusing on the direct killing effect of different types of therapeutic agents on cancer cells to the new mainstream of multi-mode and -pathway combined interventions in the microenvironment of the developing tumor. Flavonoids, with unique tricyclic structures, have diverse and extensive immunomodulatory and anti-cancer activities in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the TME. The regulation of macrophages to fight cancer is a promising immunotherapeutic strategy. This study covers the most comprehensive cognition of flavonoids in regulating TAMs so far. Far more than a simple list of studies, we try to dig out evidence of crosstalk at the molecular level between flavonoids and TAMs from literature, in order to discuss the most relevant chemical structure and its possible relationship with the multimodal pharmacological activity, as well as systematically build a structure-activity relationship between flavonoids and TAMs. Additionally, we point out the advantages of the macro-control of flavonoids in the TME and discuss the potential clinical implications as well as areas for future research of flavonoids in regulating TAMs. These results will provide hopeful directions for the research of antitumor drugs, while providing new ideas for the pharmaceutical industry to develop more effective forms of flavonoids. [Display omitted] • The most comprehensive cognition of flavonoids in regulating TAMs so far. • Flavonoids regulate macrophage recruitment, reprogramming, and activity. • Chemical structure determining the activity and efficacy between flavonoids and TAMs. • The multi-target effect of flavonoids makes them affect the TME. [ABSTRACT FROM AUTHOR]

Multi-task learning aims to tackle various tasks with branched feature sharing architectures. Considering its diversity and complexity, discriminative feature representations need to be extracted for each individual task. Fixed geometric structures as a limitation of convolutional neural networks (CNNs) in building models, is also exists and poses a severe challenge in multi-task learning since the geometric variations will augment when we deal with multiple tasks. In this paper, we go beyond these limitations and propose a novel multi-task network by introducing the deformable convolution. Our design, the Deformable Multi-Task Network (DMTN), starts with a single shared network for constructing a shared feature pool. Then, we present task-specific deformable modules to extract discriminative features to be tailored for each task from the shared feature pool. The task-specific deformable modules utilize two new parts, deformable part and alignment part, to extract more discriminative task-specific features while greatly enhancing the transformation modeling capability. Experiments conducted on various multi-task learning types demonstrate the effectiveness of the proposed method. On multiple classification tasks, semantic segmentation and depth estimation tasks, our DMTN exceeds state-of-the-art approaches against strong baselines. [ABSTRACT FROM AUTHOR]

Exosomes (EXs) are emerging as novel players in the beneficial effects induced by exercise on vascular diseases. We have recently revealed that moderate exercise enhances the function of circulating endothelial progenitor cell-derived EXs (cEPC-EXs) on protecting endothelial cells against hypoxia injury. However, the relationship between the changes of cEPC-EXs and the effects of exercise on ischemic stroke (IS) is unknown. Here, we investigated whether exercise-regulated EPC-EXs contribute to the beneficial effects of exercise on IS. C57BL/6 mice received moderate treadmill exercise (10 m/min) for 4-wks and then were subjected to middle cerebral artery occlusion (MCAO) stroke. The neurologic deficit score (NDS), infarct volume, microvessel density, cell apoptosis, angiogenesis/neurogenesis, sensorimotor functions were determined on day 2 (acute stage) and/or day 28 (chronic stage) post-stroke. The miR-126 and EPC-EX levels were analyzed by RT-PCR or nanoparticle tracking analysis combined with microbeads and used for correlation analyses. The function of EPC-EXs from exercised mice was detected in a hypoxia neuron model. Cell apoptosis, axon growth ability and gene expressions (cas-3 and Akt) were measured. Our data showed that: i) On day 2, exercised mice had decreased NDS and infarct volume, reduced cell apoptosis rate and cleaved cas-3 level, and a higher microvessel density than those in control (no-exercise) mice. The levels of EPC-EXs in plasma and brain tissue were raised and positively correlated in exercised mice. Meanwhile, the miR-126 level in cEPC-EXs and in ischemic tissue were upregulated in exercised mice. The EPC-EXs and their carried miR-126 levels negatively correlated with the infarct volume and cell apoptosis, whereas positively correlated with microvessel density. In addition, cEPC-EXs from exercised mice elicited protective effects on neurons against hypoxia-induced apoptosis and compromised axon growth ability which were blocked by miR-126 and PI3k inhibitors in vitro. ii) On day 28, exercised mice had less infarct volume, higher microvessel density, angiogenesis/neurogenesis and better sensorimotor functions. The levels of BDNF, p-TrkB/TrkB and p-Akt/Akt were upregulated in the brain of exercised mice. These recovery indexes correlated with the levels of cEPC-EXs and their miR-126. In conclusion, our data suggest that moderate exercise intervention has protective effects on the brain against MCAO-induced ischemic injury in both acute and chronic stages which might via the release of miR-126 enriched EPC-EXs. • Moderate treadmill exercise alleviated acute injury in IS. • Moderate treadmill exercise promoted chronic functional recovery in IS. • Moderate treadmill exercise enhanced the function of cEPC-EXs. • The levels of cEPC-EXs and miR-126 correlated with the acute injury index of IS. • The levels of cEPC-EXs and miR-126 correlated with the chronic recovery index of IS. [ABSTRACT FROM AUTHOR]

• Eight transcription factors (TFs) were co-overexpressed in effector T (T EFF) cells. • T EFF cells upregulated the expression of CCR7 after overexpression of specific TFs. • The gene expression profile of transfected T EFF cells was more similar to early state. • T EFF cells acquired enhanced anti-apoptotic ability after overexpression of TFs. The in vivo proliferation and viability of transfused engineered T cells markedly limits the long-term effect of adoptive cell therapy on tumors. The therapeutic efficacy and proliferative potential of T cells are reported to be dependent on the differentiation status of T cells. The T cells at the early stage of progressive differentiation have a long lifespan, strong proliferative potential, and the ability to reconstruct intact T cell subsets. Thus, they are more suitable for adoptive immunotherapy. Previously, it was difficult to obtain a sufficient number of early differentiated T cells by inhibiting the progressive differentiation of T cells or by two-step programming. A more effective strategy is to directly reprogram and dedifferentiate the easily available terminal effector T (T EFF) cells, which are generated in large numbers, into early T cells. This study attempted to overexpress eight (candidate) early differentiation-specific transcription factors (TFs) (LEF1, KLF7, ID3, EOMES, BCL6, TCF7, FOXP1, and FOXO1) in the T EFF cells, which were activated by in vitro stimulation, to promote dedifferentiation into early T cells. In the mature T EFF cells simultaneously overexpressing these specific TFs, the expression pattern of T cell differentiation markers (CCR7 and CD45RO) exhibited a tendency to change to the pattern observed during early differentiation. The transcriptome analysis revealed that the function of differentially expressed genes was mainly concentrated in the cell cycle, growth and development, and effector function. Moreover, many genes related to early differentiated T cells (such as BCL2 and PIM1) were significantly upregulated, while those related to the effector function of T EFF cells were significantly downregulated (such as GZMB , PRF1 , and GNLY). Additionally, the T EFF cells overexpressing characteristic TFs exhibited enhanced anti-apoptotic capabilities and decreased secretion of cytokines (IFN-γ and TNF-α). Based on these results, we believe that the T EFF cells were reprogrammed into a less differentiated state after overexpression of the eight specific TFs. [ABSTRACT FROM AUTHOR]