The rice ERF transcription factor OsERF922 negatively regulates resistance to Magnaporthe oryzae and salt tolerance

Rice OsERF922, encoding an APETELA2/ethylene response factor (AP2/ERF) type transcription factor, is rapidly and strongly induced by abscisic acid (ABA) and salt treatments, as well as by both virulent and avirulent pathovars of Magnaporthe oryzae, the causal agent of rice blast disease. OsERF922 is localized to the nucleus, binds specifically to the GCC box sequence, and acts as a transcriptional activator in plant cells. Knockdown of OsERF922 by means of RNAi enhanced resistance against M. oryzae. The elevated disease resistance of the RNAi plants was associated with increased expression of PR, PAL, and the other genes encoding phytoalexin biosynthetic enzymes and without M. oryzae infection. In contrast, OsERF922-overexpressing plants showed reduced expression of these defence-related genes and enhanced susceptibility to M. oryzae. In addition, the OsERF922-overexpressing lines exhibited decreased tolerance to salt stress with an increased Na+/K+ ratio in the shoots. The ABA levels were found increased in the overexpressing lines and decreased in the RNAi plants. Expression of the ABA biosynthesis-related genes, 9-cis-epoxycarotenoid dioxygenase (NCED) 3 and 4, was upregulated in the OsERF922-overexpressing plants, and NCED4 was downregulated in the RNAi lines. These results suggest that OsERF922 is integrated into the cross-talk between biotic and abiotic stress-signalling networks perhaps through modulation of the ABA levels

Simulation of Electrochemical Impedance Spectra of Solid Oxide Fuel Cells Using Transient Physical Models

A general electrochemical impedance spectroscopy ͑EIS͒ modeling approach by directly solving a one-dimensional transient model based on physical conservation laws was applied for simulating EIS spectra of an anode-supported solid oxide fuel cell ͑SOFC͒ button cell consisting of Ni-yttria-stabilized zirconia ͉Ni-scandia-stabilized zirconia ͑ScSZ͉͒ScSZ͉lanthanum strontium manganate ͑LSM͒-ScSZ multiple layers. The transient SOFC model has been solved for imposed sinusoidal voltage perturbations at different frequencies. The results have then been transformed into EIS spectra. Six parameters had to be tuned ͑three for the cathode and three for the anode͒ and have been estimated using data from a symmetric cathode cell and from a button cell. The experimental and simulated EIS spectra were in good agreement for a range of temperatures ͑750-850°C͒, of feed compositions ͑mixture of H 2 /H 2 O/N 2 ͒, and of oxidants ͑air and oxygen͒. This approach can help in interpreting EIS spectra, as illustrated by identifying the contribution of transport limitation. Fuel cell electrochemical systems are usually complex and are governed by coupled physicochemical processes such as chemical and electrochemical reactions, charge transport, and mass transport. 1,2 Because polarization curves can only provide a general description of the cell performance, electrochemical impedance spectroscopy ͑EIS͒ has become widely used in fuel cell research and development because it involves a relatively simple electrical measurement that gives detailed information about the fuel cell system, from mass-transport properties, chemical reaction rates, and dielectric properties to defects, microstructure, compositional influences, etc. 3 In this dynamic technique, usually a voltage perturbation is applied to a system and the amplitude and phase shift of the resulting current response are measured. Measurements can be conducted over a wide range of frequencies, resulting in the construction of impedance spectra. 5 Although the approach is useful and quite powerful, it often has limitations such as: 1. The approach can lead to ambiguities in data interpretations because the equivalent circuits are seldom unique except for only the simplest circuits. An equivalent circuit involving several circuit elements could often be rearranged in various configurations while still yielding the same impedance. 2. Detailed physical and chemical processes in the system cannot be predicted by equivalent-circuit models. For instance, the effects of current distributions and concentration distributions cannot be taken into account when interpreting data from equivalent-circuit models. 3. The measured system could only be approximated by circuit elements when assuming linear response of the system. The impedance is supposed to be independent of the amplitude of the applied signals. However, the electrochemical system could be highly nonlinear, especially for sinusoidal perturbations with high amplitudes. It was suggested that nonlinear EIS ͑NLEIS͒ measurements have several potential advantages. To investigate solid oxide fuel cell ͑SOFC͒ electrode reaction kinetics, Miterdorfer and Gauckler 7-9 used a state-space model ͑SSM͒, which is widely used in control theory for solving complex differential equations. Bieberle and Gauckler 5 studied in depth elementary electrochemical reactions in SOFC anode by both experimental and SSM approaches. To simulate the electrochemical impedance spectra, the models were solved directly through the SSM approach. Bessler 10 presented a computational method for simulating EIS spectra based on transient numerical simulations of the reaction system. The impedance was then calculated in the time domain from the simulated periodic response of the system, maintaining its full nonlinear response. This method has been further validated by detailed modeling studies on SOFC EIS spectra achieved from gas-transport processes. 11 Gewies et al. 12 also applied this method on Ni/yttria-stabilized zirconia ͑YSZ͒ cermet anodes. Zhu and Kee 13 developed a time-accurate model to analyze EIS spectra in anode-supported button cells with internal methane reforming. This model represented significant advantages regarding physical conservation laws, porous media transport within the electrode, and heterogeneous chemistry reactions mechanisms, all of those being solved in the time domain. However, the spatial variations of ion and electron transport throughout the electrode structures were not considered. In this paper, a general approach for EIS spectra simulation is applied by solving a comprehensive set of coupled transient models based on physical conservation laws. This simulation approach is illustrated by considering a transient model of an anode-supported SOFC button cell consisting of Ni-YSZ͉Ni-scandia-stabilized zirconia ͑ScSZ͉͒ScSZ͉LSM-ScSZ multiple layers. The simulation results of the EIS spectra were then compared to the measured EIS spectra under various conditions to prove the validity of both the transient model and the EIS simulation approach. Experimental Testing cell.-The anode-supported SOFC button cell used in this study consisted of a Ni/YSZ anode support layer ͑680 m͒, a Ni/ScSZ anode active interlayer ͑15 m͒, a ScSZ thin-film electrolyte layer ͑20 m͒, and a lanthanum strontium manganate ͑LSM͒/ ScSZ cathode layer ͑15 m͒. 14,1

Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2

Objective: AIP1 expression is downregulated in human atherosclerotic plaques and global deletion of AIP1 in mice exacerbates atherosclerosis in ApoE-KO mouse models. However, the direct role of AIP1 in endothelium, vascular remodeling and associated vascular diseases has not been determined.Approach and Results: We used endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice to define the role of AIP1 in vascular remodeling and intima-media thickening in a mouse carotid artery ligation model characterized by both neointimal hyperplasia and inward vessel remodeling. Compared to WT littermates, AIP1-ECKO mice had 2.2-fold larger intima area and 4.4-fold thicker intima as measured by intima/media ratio in arteries with more proliferating vascular smooth muscle cells (VSMCs) at week 2–4 post-injury. Increased reactive oxygen species (ROS) in endothelium at early time points induced inflammation and vessel dysfunction in AIP1-ECKO prior to VSMC accumulations. Moreover, knockdown of AIP1 in human EC enhanced ROS generation which was attenuated by co-silencing of NOX2. Mechanistically, AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production.Conclusion: Our study supports that AIP1 regulates vascular remodeling with intima-media thickening by suppressing endothelial NOX2-dependent oxidative stress.Highlights:•In a carotid ligation model, endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice had much larger media area, thicker vessel wall and augmented neointima formation.•Increased production of reactive oxygen species in vascular EC at early time points concomitant with vessel dysfunction in AIP1-ECKO.•AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production

How Can We Understand the Past from Now On? Three-Dimensional Modelling and Landscape Reconstruction of the Shuanghuaishu Site in the Central Plains of China

The Shuanghuaishu (SHS) site in China is one of the 100 most important archaeological discoveries over the past 100 years; its historical heritage can be traced directly back 5300 years. Understanding the early landscape of the site would provide important information about the origin of Chinese civilization. The SHS site is buried and surface traces are difficult to see; therefore, we attempted to reconstruct the early landscape of the site based on a current surface landscape model and environmental archaeological analysis. We created a modern three-dimensional (3D) landscape model of the study area from high spatial resolution unmanned aerial vehicle (UAV) aerial photographs and analysed the distance change between the Yellow River and SHS site in the past 60 years from CORONA and Landsat images. By combining environmental archaeological survey results, archaeological excavation data, relevant papers, and field measurements, we reconstructed the paleotopography of the SHS site during the Yangshao period (7000–5000 aBP). On this basis, 3D natural and human landscapes during the Yangshao period were rebuilt. The results show that (1) Satellite images acquired at different resolutions can provide multiscale spatial information about the site, and high-precision models of current conditions can be quickly generated from UAV aerial photography. (2) From 1960 to 2020, the shortest distance between the SHS site and the Yellow River was approximately 512 m. The location of bedrock on Mang Mountain can be used to infer the early extent of the northern terrace at the site. (3) Environmental archaeology provided information about the palaeoenvironment of the site area. By incorporating spatial information technology and 3D visualization, we can better restore the early landscape of the SHS site. Our work integrates environmental archaeology, field archaeology, and spatial technology, enabling data and modelling support for the visual interpretation of the SHS site

Predictive value of volumetric parameters based on 18F-PSMA-1007 PET/CT for prostate cancer metastasis

Purpose of the reportTo explore the value of 18F-labeled prostate-specific membrane antigen (PSMA-1007) positron emission tomography (PET)/computed tomography (CT), the maximum standardized uptake value (SUVmax) of the primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) for predicting prostate cancer (PCa) metastasis and follow-up evaluation in primary PCa lesions.Materials and methods18F-PSMA-1007 PET/CT data of 110 consecutive newly diagnosed PCa patients were retrospectively analyzed. Patients were divided into non-metastatic, oligometastatic, and extensive metastatic groups. The predictive power was assessed using the receiver operating characteristic curve. Multi-group one-way analysis of variance and post-hoc tests were used to compare the groups. Patients were monitored post-therapy to evaluate treatment effectiveness.ResultsAmong the 110 patients, 66.4% (73) had metastasis (29 oligometastatic, 44 extensive metastasis). AUCs for Gleason score (GS), total prostate-specific antigen(TPSA), SUVmax, TL-PSMAp, and PSMA-TVp were 0.851, 0.916, 0.834, 0.938, and 0.923, respectively. GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp were significantly different among the groups. In the post-hoc tests, differences in GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp between the non-metastatic and oligometastatic groups and non-metastatic and extensive metastatic groups were significant (P<0.010). Differences in TL-PSMAp and PSMA-TVp between oligometastatic and extensive metastatic groups were significant (P=0.039 and 0.015, respectively), while those among GS, TPSA, and SUVmax were not. TL-PSMAp and PSMA-TVp distinguished between oligometastatic and extensive metastases, but GS, TPSA, and SUVmax did not. In individuals with oligometastasis, the implementation of active treatment for both primary and metastatic lesions may result in a more favorable prognosis.Conclusions18F-PSMA-1007 PET/CT volumetric parameters PSMA-TVp and TL-PSMAp can predict PCa oligometastasis

CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells. CC-223 concurrently blocked mTORC1 and mTORC2 activation, and its cytotoxicity against HCC cells was much more potent than the traditional mTORC1 inhibitors (RAD001 and rapamycin). Further studies demonstrated that CC-223 disrupted mitochondrial function, and induced mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production. On the other hand, ROS scavengers and mPTP blockers (cyclosporin A or sanglifehrin A) largely attenuated CC-223-induced HepG2 cell apoptosis. In vivo studies showed that oral administration of CC-223 dramatically inhibited growth of HepG2 xenografts in severe combined immuno-deficient (SCID) mice. mTORC1/2 activation was also blocked in xenografts with CC-223 administration. Together, CC-223 simultaneously blocks mTORC1/2 and efficiently inhibits human HCC cells