•High-resolution P-wave velocity model of Northeast Asia obtained by using a large dataset.•The subducting Pacific slab has partly sunk into the lower mantle because of the plate suddenly changed its ...direction.•Evolution of the North-South Gravity lineament is related to the Pacific or Paleo-Pacific plate subduction.
A high-resolution model of 3-D P-wave velocity structure beneath Northeast Asia and adjacent regions is determined by using 244,180 arrival times of 14,163 local and regional earthquakes and 319,857 relative travel-time residuals of 9988 teleseismic events recorded at ∼2100 seismic stations in the study region. Our tomographic results reveal the subducting Pacific slab clearly as a prominent high-velocity anomaly from the Japan Trench to the North-South Gravity lineament (NSGL) in East China. The NSGL is roughly coincident with the western edge of the stagnant Pacific slab in the mantle transition zone (MTZ). The subducting Pacific slab has partly sunk into the lower mantle beneath Northeast China, but under the Sino-Korean Craton the slab lies horizontally in the MTZ. The NSGL, as an important tectonic line in Mainland China, is marked by sharp differences in the surface topography, gravity anomaly, crustal and lithospheric thickness and mantle seismic velocity from the east to the west. These features of the NSGL and large-scale hot and wet upwelling in the big mantle wedge (BMW) in the east of the NSGL are all related to the subduction processes of the Western Pacific plate. The Changbai intraplate volcanic group is underlain by a striking low-velocity anomaly from the upper MTZ and the BMW up to the surface, and deep earthquakes (410–650 km depths) occur actively in the subducting Pacific slab to the east of the Changbai volcano. We propose that the Changbai volcanic group is caused by upwelling of hot and wet asthenospheric materials and active convection in the BMW. The formation of other volcanic groups in the east of the NSGL is also associated with the subduction-driven corner flow in the BMW.
Germination is a plant developmental process by which radicle of mature seeds start to penetrate surrounding barriers for seedling establishment and multiple environmental factors have been shown to ...affect it. Little is known how high salinity affects seed germination of C4 plant, Zea mays. Preliminary germination assay suggested that isolated embryo alone was able to germinate under 200 mM NaCl treatment, whereas the intact seeds were highly repressed. We hypothesized that maize endosperm may function in perception and transduction of salt signal to surrounding tissues such as embryo, showing a completely different response to that in Arabidopsis. Since salt response involves ABA, we analysed in vivo ABA distribution and quantity and the result demonstrated that ABA level in isolated embryo under NaCl treatment failed to increase in comparison with the water control, suggesting that the elevation of ABA level is an endosperm dependent process. Subsequently, by using advanced profiling techniques such as RNA sequencing and SWATH‐MS‐based quantitative proteomics, we found substantial differences in post‐transcriptional and translational changes between salt‐treated embryo and endosperm. In summary, our results indicate that these regulatory mechanisms, such as alternative splicing, are likely to mediate early responses to salt stress during maize seed germination.
This study demonstrated that maize endosperm may function in sensation and transduction of salt signal to surrounding tissues during salt stress, which is a completely different responsive model from that of Arabidopsis.
Oxidative stress has been considered to be closely related to spaceflight-induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial ...osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity-induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca
overload, and the latter was found to be caused by increased activity of Ca
channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A-elicited Ca
influx. Supplementation of HC-067047, a specific antagonist of TRPV4, attenuated microgravity-induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity-induced shortening of primary cilia led to increased TRPV4 levels and Ca
influx. When primary cilia were protected by miR-129-3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity-induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity-induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca
overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts.
LINKED CONTENT
This article is linked to Kao et al and Tseng & Kao papers. To view these articles, visit https://doi.org/10.1111/apt.16097 and https://doi.org/10.1111/apt.16162
New major and trace elemental, Sr–Nd–Pb isotope, and zircon U–Pb geochronological and Hf–O isotope data of post-collisional potassic and ultrapotassic volcanic rocks (PVRs and UPVs, respectively) ...along with geochemical data of PVRs, UPVs, and Mg-rich potassic rocks (MPRs) in the literature are used to constrain their mantle source and genesis. The PVRs, UPVs, and MPRs share similar geochemical features but with some discrepancies, suggesting that they were derived from subcontinental lithospheric mantle (SCLM) with isotopic heterogeneity resulting from the varying contributions of subducted Indian lower crust into the mantle source (ca. 6–20%, ca. 8–30%, and ca. 9–30%, respectively). The zircon Hf–O isotopic compositions of these rocks can be classified into two groups, including Group I rocks with high δ18O (6.7–11.3‰), low εHf(t) (−17.0 to −12.0), and old Hf crustal model ages (1.87–2.19Ga) that indicate an ancient SCLM source, and Group II rocks with δ18O values of 6.8–10.7‰, εHf(t) values of −11.8 to −6.3, and younger Hf crustal model ages (1.50–1.86Ga). The negative correlation defined by δ18O and εHf(t) of Group II samples suggests a two-component mixing between mantle- and crust-derived melts, in which the latter would be the subducted Indian lower crust as indicated by the similar negative εHf(t) values between Group II samples (−11.8 to −6.3) and the High Himalayan gneiss (−14.2 to +0.3). Thus we propose two enrichment events to account for the Hf–O isotopic compositions of the PVRs and UPVs/MPRs: the first involves the enrichment of the overlying SCLM that was metasomatized by fluids derived from dehydration of the subducted Indian lower crust, and the second invokes the enrichment of the overlying SCLM metasomatized by melts of the already dehydrated different proportions of the Indian lower crust. We argue that break-off of the northwards subducted Indian Plate in the early Miocene caused the asthenospheric upwelling under the Indian plate through slab window, resulting in varying degrees of partial melting of the overlying metasomatized heterogeneous SCLM to produce the primitive magmas of the PVRs, UPVs, and MPRs in an extensional setting. These observations and interpretations imply that the Indian lower crust was subducted beneath the Lhasa terrane in the Early–Middle Miocene.
•First reporting the zircon O isotopic compositions of the PVRs and UPVs•Suggesting a uniform model for the origin of the K-rich lavas•Favoring the Indian lower crust which was subducted beneath the Lhasa terrane
Display omitted
Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the ...DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.
Somatic inactivating mutations of ARID1A, a SWI/SNF chromatin remodeling gene, are prevalent in human endometrium-related malignancies. To elucidate the mechanisms underlying how ARID1A deleterious ...mutation contributes to tumorigenesis, we establish genetically engineered murine models with Arid1a and/or Pten conditional deletion in the endometrium. Transcriptomic analyses on endometrial cancers and precursors derived from these mouse models show a close resemblance to human uterine endometrioid carcinomas. We identify transcriptional networks that are controlled by Arid1a and have an impact on endometrial tumor development. To verify findings from the murine models, we analyze ARID1A
and ARID1A
human endometrial epithelial cells. Using a system biology approach and functional studies, we demonstrate that ARID1A-deficiency lead to loss of TGF-β tumor suppressive function and that inactivation of ARID1A/TGF-β axis promotes migration and invasion of PTEN-deleted endometrial tumor cells. These findings provide molecular insights into how ARID1A inactivation accelerates endometrial tumor progression and dissemination, the major causes of cancer mortality.
Abstract
DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly ...selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.
Graphical Abstract
Graphical Abstract
Thiazole orange-based small molecules engineered to possess the functional property of two-directional and multi-site interactions with G4–DNA structures achieving excellent G4-target selectivity and in vivo antitumor activity against breast cancer.
With the rapid development of functional requirements in the emerging Industry 4.0 era, modern industrial control systems (ICSs) are no longer isolated islands, making them more vulnerable to various ...cyberattack threats. Cyberattacks on ICSs may have disruptive consequences, such as significant social and economic losses. To proactively address the security issue of ICSs, this article presents a unified architectural approach from the perspectives of cyberthreats on ICSs, security-related ICS technologies, and methods for ICSs. It incorporates secure networks, secure control systems, secure physical processes, and their interactions seamlessly into a unified framework. To increase the resistance of ICSs against intrusions, the network security in our architectural approach is to secure the data in motion through the integration of secure network architecture, secure industrial network protocols, and secure end-to-end communications. The protection of control systems in our architectural approach is risk-based and hierarchical and encompasses prevention- and tolerance-centric defenses. It provides a layer-by-layer defense so that an acceptable level of cybersecurity risk is achieved and maintained. Aiming to maintain the stable operation of physical ICS processes, the secure control in our architectural approach implements a security process against process-aware attacks through a resilient safety control scheme. The global and systematic architectural approach presented in this article for the ICS cybersecurity will help facilitate the design and implementation of cyberattack-resilient ICSs in the networked world. For further development of ICS security technologies, emerging challenges are identified and discussed to motivate future research efforts.
A unique heterostructure is developed based on a 3D photoactive semiconductor and a 0D Cu2O QDs for superb photocatalytic reduction CO2 into CO. It reported a novel and simple method to prepare a 3D ...g-C3N4 foam with micron-sized porous structures using ultrastable foam as a soft template for the first time. Moreover, Cu2O QDs are loaded onto 3D g-C3N4 foam through a simple photodeposition strategy. Systematically characterization demonstrated that g-C3N4 foam not only act as an excellent carrier for Cu2O QDs, but also greatly improve the photocatalytic performance by enhancing CO2 adsorption and gas transfer. Simultaneously, the rationally designed g-C3N4 foam/Cu2O QDs exhibited notablely enhancement in photocatalytic performance with 3.9 times and 11 times higher than that of g-C3N4 foam and bulk g-C3N4 powder. The excellent photocatalytic activity can be attributed to the unique porous structure and the synergistic effect between g-C3N4 foam and Cu2O QDs, which can speed up the transfer of charge carriers and urged the cumulation of photo-generated electrons on the Cu2O QDs. Our work provides new ideas for constructing 0D/3D hierarchical photocatalytic systems, which may provide guidance on designing efficient photocatalysts to maximize photocatalyst kinetics.
Display omitted
•Cu2O QDs modified 3D g-C3N4 foam was facilely synthesized.•Photocatalytic reduction CO2 was enhanced by excellent CO2 adsorption performance.•Synergistic effect between g-C3N4 foam and Cu2O QDs was proposed in this system.