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Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells. STAT3 and SOX-5 may mediate Th17 cell differentiation through the induction of BRG1-mediated chromatin remodeling of RORCE2. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive study on the numerical and parametric study of geocell-reinforced cohesive soil beds, focusing on different infill materials. The numerical calculations were validated against model test results using FLAC3D software. Subsequently, the verified model was expanded to the geocell-reinforced cohesive soil beds. Six cases were simulated to investigate the reinforced performance, including pressure-settlement responses, bearing capacity improvement factor, settlement reduction percentage, and surface deformation. The numerical findings emphasize that the significance of superior geocell reinforcement should not overshadow the consideration of soil infill's mechanical properties. In the case of cohesive soil as the infill material, the poor improvement in geocell-reinforced performance may be attributed to its low modulus and cohesion. Parametric studies suggest that geocells significantly impact reinforced performance when the infill material consists of foundation soil with a higher modulus and lower cohesion. Further, according to this numerical study, cohesionless soil with a modulus of 20 MPa and friction of 40° is the optimum infill soil in pockets to reinforce cohesive soil beds. [ABSTRACT FROM AUTHOR]

Ancient whole-genome duplications (WGDs) characterize many large angiosperm lineages, including angiosperms themselves. Prominently, the core eudicot lineage accommodates 70% of all angiosperms and shares ancestral hexaploidy, termed gamma. Gamma arose via two WGDs that occurred early in eudicot history; however, the relative timing of these is unclear, largely due to the lack of high-quality genomes among early-diverging eudicots. Here, we provide complete genomes for Buxus sinica (Buxales) and Tetracentron sinense (Trochodendrales), representing the lineages most closely related to core eudicots. We show that Buxus and Tetracentron are both characterized by independent WGDs, resolve relationships among early-diverging eudicots and their respective genomes, and use the RACCROCHE pipeline to reconstruct ancestral genome structure at three key phylogenetic nodes of eudicot diversification. Our reconstructions indicate genome structure remained relatively stable during early eudicot diversification, and reject hypotheses of gamma arising via inter-lineage hybridization between ancestral eudicot lineages, involving, instead, only stem lineage core eudicot ancestors. Gamma triplication arises via two whole-genome duplications early in eudicot history, but the relative timing of these is unclear. Here, the authors report the genomes of Buxales and Trochodendrales and reject the hypothesis of gamma arising via inter-lineage hybridization between ancestral eudicot lineages. [ABSTRACT FROM AUTHOR]

In-situ bioprinting is attractive for directly depositing the therapy bioink at the defective organs to repair them, especially for occupations such as soldiers, athletes, and drivers who can be injured in emergency. However, traditional bioink displays obvious limitations in its complex operation environments. Here, we design a bioconcrete bioink with electrosprayed cell-laden microgels as the aggregate and gelatin methacryloyl (GelMA) precursor solution as the cement. Promising printability is guaranteed with a wide temperature range benefiting from robust rheological properties of photocrosslinked microgel aggregate and fluidity of GelMA cement. Composite components simultaneously self-adapt to biocompatibility and different tissue mechanical microenvironment. Strong binding on tissue-hydrogel interface is achieved by hydrogen bonds and friction when the cement is photocrosslinked. This bioink owns good portability and can be easily prepared in urgent accidents. Meanwhile, microgels can be cultured to mini tissues and then mixed as bioink aggregates, indicating our bioconcrete can be functionalized faster than normal bioinks. The cranial defects repair results verify the superiority of this bioink and its potential in clinical settings required in in-situ treatment. Bioinks used in current in-situ bioprinting have limitations when applied to complex operational environments. Here, the authors report on the creation of a microgel reinforced GelMA bioink which can be simply prepared and used in different biomedical settings. The application is demonstrated in a cranial defect model. [ABSTRACT FROM AUTHOR]

In the past decade, the precise measurement of the lastly known neutrino mixing angle θ 13 has enabled the resolution of neutrino mass hierarch (MH) at medium-baseline reactor neutrino oscillation (MBRO) experiments. Recent calculations of the reactor neutrino flux predict percent-level sub-structures in the ν ¯ e spectrum due to Coulomb effects in beta decay. Such fine structure in the reactor spectrum has been an issue of concern for efforts to determine the neutrino MH for the MBRO approach, the concern being that the sub-dominant oscillation pattern used to discriminate different hierarchies will be obscured by fine structure. The energy resolutions of current reactor experiments are not sufficient to measure such fine structure, and therefore the size and location in energy of these predicted discontinuities has not been confirmed experimentally. There has been speculation that a near detector is required with sufficient energy resolution to resolve the fine structure. This article studies the impact of fine structure on the resolution of MH, based on predicted reactor neutrino spectra, using the measured spectrum from Daya Bay as a reference. We also investigate how a near detector could improve the sensitivity of neutrino MH resolution based on various assumptions of near detector energy resolution. [ABSTRACT FROM AUTHOR]

Abiotic stresses, including drought and salinity, trigger a complex osmotic-stress and abscisic acid (ABA) signal transduction network. The core ABA signalling components are snf1-related protein kinase2s (SnRK2s), which are activated by ABA-triggered inhibition of type-2C protein-phosphatases (PP2Cs). SnRK2 kinases are also activated by a rapid, largely unknown, ABA-independent osmotic-stress signalling pathway. Here, through a combination of a redundancy-circumventing genetic screen and biochemical analyses, we have identified functionally-redundant MAPKK-kinases (M3Ks) that are necessary for activation of SnRK2 kinases. These M3Ks phosphorylate a specific SnRK2/OST1 site, which is indispensable for ABA-induced reactivation of PP2C-dephosphorylated SnRK2 kinases. ABA-triggered SnRK2 activation, transcription factor phosphorylation and SLAC1 activation require these M3Ks in vitro and in plants. M3K triple knock-out plants show reduced ABA sensitivity and strongly impaired rapid osmotic-stress-induced SnRK2 activation. These findings demonstrate that this M3K clade is required for ABA- and osmotic-stress-activation of SnRK2 kinases, enabling robust ABA and osmotic stress signal transduction. SnRK2 kinases activate abiotic stress responses in plants following ABA-dependent phosphatase inhibition or ABA-independent osmotic stress signalling. Here Takahashi et al. show that MAPKK-kinases phosphorylate and activate SnRK2s thus enabling robust ABA and osmotic stress signal transduction. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the most common outcome of chronic kidney disease (CKD), while the pathogenesis of renal fibrosis is not fully understood. In this study, we first showed that the progress of renal fibrosis was positively related to serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there was a close correlation between serum indoxyl sulfate levels and β-catenin expression in the kidneys ( r = 0.908, p < 0.001) of CKD patients. We then demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day) for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which was accompanied by a significant activation of Wnt/β-catenin signaling. In vitro investigations in human renal tubular HK-2 cells revealed that indoxyl sulfate exhibited a potent ability to induce Wnt/β-catenin activation through the downregulation of sFRP5, a gene that codes for an extracellular antagonist of Wnt signaling, by increasing the DNA methylation level of its promoter CpG islands. The increased expression of DNA methyltransferases following the activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation of sFRP5 induced by indoxyl sulfate. Conversely, treatment with 5-aza-2′-deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced indoxyl sulfate-induced sFRP5 downregulation and Wnt/β-catenin activation. In vivo, intraperitoneal injections of recombinant sFRP5 protein or 5-aza-2′-deoxycytidine substantially alleviated renal fibrosis in indoxyl sulfate-treated uninephrectomized mice. Our results suggest that indoxyl sulfate promotes renal fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter the activation of Wnt/β-catenin signaling. These findings provide new insights into the pathogenesis of renal fibrosis in CKD patients. Key messages: [ABSTRACT FROM AUTHOR]

Renal interstitial fibrosis is a major pathologic feature of diabetic nephropathy, while the pathogenesis and therapeutic interventions of diabetic renal interstitial fibrosis are not well established. In this study, we first demonstrated that high glucose could induce renal fibroblast (NRK-49F) cell proliferation and activation to myofibroblasts, accompanied by a significant increase in the intracellular levels of reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). ROS-mediated ERK1/2 activation was found to play a crucial role in high glucose-induced fibroblast proliferation and activation. Resveratrol, like the NOX4-targeting small interfering RNA (siRNA), markedly inhibited high glucose-induced fibroblast proliferation and activation by reducing NOX4-derived ROS production. It was then revealed that the increase in the expression of NOX4 induced by high glucose was due to the inactivation of AMP-activated protein kinase (AMPK), which could be reversed by resveratrol. Further in vivo investigation demonstrated that resveratrol treatment significantly attenuated renal fibrosis in db/db mice, accompanied by an evident increase in phospho-AMPK and decrease in NOX4. In summary, our results suggest that high glucose can directly promote renal fibroblasts proliferation and activation in a ROS-dependent manner, and resveratrol is a potential therapeutic agent against diabetic renal fibrosis via regulation of AMPK/NOX4/ROS signaling. Key message: [ABSTRACT FROM AUTHOR]

Vitis vinifera L. represents an economically important fruit species. Grape and wine flavour is made from a complex set of compounds. The acidity of berries is a major parameter in determining grape berry quality for wine making and fruit consumption. Despite the importance of malic and tartaric acid (TA) storage and transport for grape berry acidity, no vacuolar transporter for malate or tartrate has been identified so far. Some members of the aluminium-activated malate transporter (ALMT) anion channel family from Arabidopsis thaliana have been shown to be involved in mediating malate fluxes across the tonoplast. Therefore, we hypothesised that a homologue of these channels could have a similar role in V. vinifera grape berries. We identified homologues of the Arabidopsis vacuolar anion channel AtALMT9 through a TBLASTX search on the V. vinifera genome database. We cloned the closest homologue of AtALMT9 from grape berry cDNA and designated it VvALMT9. The expression profile revealed that VvALMT9 is constitutively expressed in berry mesocarp tissue and that its transcription level increases during fruit maturation. Moreover, we found that VvALMT9 is targeted to the vacuolar membrane. Using patch-clamp analysis, we could show that, besides malate, VvALMT9 mediates tartrate currents which are higher than in its Arabidopsis homologue. In summary, in the present study we provide evidence that VvALMT9 is a vacuolar malate channel expressed in grape berries. Interestingly, in V. vinifera, a tartrate-producing plant, the permeability of the channel is apparently adjusted to TA. [ABSTRACT FROM AUTHOR]

We prepared highly-ordered titanium dioxide nanotube arrays (TNAs) by anodizing Ti foils in F-containing electrolytes. The crystalline nature and morphology of the TNAs were studied using X-ray diffraction patterns and scanning electron microscopy. We found the morphology of TNAs affects the light-to-electricity conversion efficiency ( η) of dye-sensitized solar cells (DSSCs). The efficiency of DSSCs reached 5.95% under the condition of light illuminated from the counter electrode. The high efficiency of TNA-based DSSCs was attributed to the neat top surface of TNAs, which allows more dye molecule loading on the surface of the TiO nanotubes, and fewer electron recombination centers and a low interface resistance of integrated TNAs. [ABSTRACT FROM AUTHOR]

To use the existing Automatic Identification System (AIS) shore stations for positioning so that the AIS can be used as an additional land-based positioning system for coastal vessels is a cutting-edge research topic, responding to the call of the International Maritime Organization (IMO). In order to use the ship-borne AIS for positioning function, a holographic detection of AIS real-time signal based on sparse representation is presented in this paper. Considering the working environment and the requirement of AIS real-time signal processing, a novel fast noise resistance Orthogonal Matching Pursuit (OMP) algorithm is presented. Furthermore, the choice and detection of the timestamp of the reconstructed signal is analyzed and carried out which will be used in the ranging system. The experiment results indicate that the proposed fast noise resistance OMP algorithm can greatly reduce the processing time, and the difference in processing time increases with the number of iterations. The improvement in noise immunity is also obvious, and the error rate reduces at about 9% under the same SNR. The timestamp of the reconstructed signals can be detected successfully. It shows that the holographic detection of AIS real-time signal is achieved satisfactorily. [ABSTRACT FROM AUTHOR]