Inhibitory effect of tetramethylpyrazine combined with propranolol on murine hemangioma endothelial cells

Purpose: To study the inhibitory effect of different doses of tetramethylpyrazine (TMP) combined with the beta-blocker, propranolol (Pro) on hemangioma endothelial (EOMA) cells. Methods: EOMA cells were cultured in vitro with varying doses of TMP and Pro (5, 10, 20 and 40 uM). The effect of treatments on cell proliferation was assessed by MTT assay, while cell apoptosis was assayed by flow cytometry. The expressions of Bcl-2, Bax, p-mTOR), total-mammalian target of rapamycin (t-mTOR, p-p70S6) and total-p70 ribosomal protein S6 (t-p70S6) proteins were determined using Western blot. Results: MTT data showed that when used alone, TMP had no significant inhibitory effect on EOMA cells (p > 0.05). However, when TMP was combined with propranolol, there was significant inhibition of EOMA cells, and that the inhibition is dependent on TMP dose. Flow cytometry results showed that the combination of TMP and Pro induced EOMA cell apoptosis dose-dependently (p < 0.05). Moreover, TMP dose-dependently inhibited the phosphorylation of mTOR and p70S6 in EOMA cells, and enhanced Bax expression, but downregulated Bcl-2 (p < 0.05). Conclusion: These results suggest that TMP enhances the inhibitory influence of Pro p-mTOR and pp-70S6 in EOMA cells in a dose-dependent manner. Thus, TMP may enhance Pro-induced inhibition of the growth of endothelial cells, and promote apoptosis through suppression of activation of PI3K/AKT signal route. These findings provide a theoretical basis for the clinical application of TMP/Pro combination for the treatment of hemangioma

In search for the missing arc root of the Southern California Batholith: P-T-t evolution of upper mantle xenoliths of the Colorado Plateau Transition Zone

Xenolith and seismic studies provide evidence for tectonic erosion and eastward displacement of lower crust-subcontinental mantle lithosphere (LC-SCML) underlying the Mojave Desert Region (i.e. southern California batholith (SCB)). Intensified traction associated with the Late Cretaceous flattening of the subducting Farallon plate, responsible for deforming the SW U.S., likely played a key role in “bulldozing” the tectonically eroded LC-SCML ∼500 km eastwards, to underneath the Colorado Plateau Transition Zone (CPTZ) and further inboard. The garnet clinopyroxenite xenoliths from two CPTZ localities, Chino Valley and Camp Creek (central Arizona), provide a rare glimpse of the material underlying the CPTZ. Thermodynamic modeling, in addition to major and trace element thermobarometry, suggests that the xenoliths experienced peak conditions of equilibration at 600-900 °C and 12-28 kbar. These peak conditions, along with the composition of the xenoliths (type “B” garnet and diopsidic clinopyroxene) strongly suggest a continental arc residue (“arclogite”), rather than a lower plate subduction (“eclogite”), origin. A bimodal zircon U-Pb age distribution with peaks at ca. 75 and 150 Ma, and a Jurassic Sm-Nd garnet age (154 ± 16 Ma, with initial εNd value of +8) overlaps eastern SCB pluton ages and suggests a consanguineous relationship. Cenozoic zircon U-Pb ages, REE geochemistry of zircon grains, and partially re-equilibrated Sm-Nd garnet ages indicate that displaced arclogite remained at elevated PT conditions (>700 °C) for 10s of Myr following its dispersal until late Oligocene entrainment in host latite. With a ∼100 Myr long thermal history overlapping that of the SCB and the CPTZ, these assemblages also contain evidence for late-stage hydration (e.g. secondary amphibole), potentially driven by de-watering of the Laramide slab. In light of these results, we suggest that the CPTZ arclogite originates from beneath the eastern half of the SCB, where it began forming in Late Jurassic time as mafic keel to continental arc magmas. The displacement and re-affixation of the arclogites further inboard during the Late Cretaceous flat slab subduction, might have contributed to the tectonic stability of the Colorado Plateau relative to adjacent geologic provinces through Laramide time and likely preconditioned the region to Cenozoic tectonism, e.g. present-day delamination beneath the plateau, high-magnitude extension and formation of metamorphic core complexes

Characterization of Duck (Anas platyrhynchos) Short Tandem Repeat Variation by Population-Scale Genome Resequencing

Short tandem repeats (STRs) are usually associated with genetic diseases and gene regulatory functions, and are also important genetic markers for analysis of evolutionary, genetic diversity and forensic. However, for the majority of STRs in the duck genome, their population genetic properties and functional impacts remain poorly defined. Recent advent of next generation sequencing (NGS) has offered an opportunity for profiling large numbers of polymorphic STRs. Here, we reported a population-scale analysis of STR variation using genome resequencing in mallard and Pekin duck. Our analysis provided the first genome-wide duck STR reference including 198,022 STR loci with motif size of 2–6 base pairs. We observed a relatively uneven distribution of STRs in different genomic regions, which indicates that the occurrence of STRs in duck genome is not random, but undergoes a directional selection pressure. Using genome resequencing data of 23 mallard and 26 Pekin ducks, we successfully identified 89,891 polymorphic STR loci. Intensive analysis of this dataset suggested that shorter repeat motif, longer reference tract length, higher purity, and residing outside of a coding region are all associated with an increase in STR variability. STR genotypes were utilized for population genetic analysis, and the results showed that population structure and divergence patterns among population groups can be efficiently captured. In addition, comparison between Pekin duck and mallard identified 3,122 STRs with extremely divergent allele frequency, which overlapped with a set of genes related to nervous system, energy metabolism and behavior. The evolutionary analysis revealed that the genes containing divergent STRs may play important roles in phenotypic changes during duck domestication. The variation analysis of STRs in population scale provides valuable resource for future study of genetic diversity and genome evolution in duck

Insight into nickel-cobalt oxysulfide nanowires as advanced anode for sodium-ion capacitors

Transition metal oxides have a great potential in sodium-ion capacitors (SICs) due to their pronouncedly higher capacity and low cost. However, their poor conductivity and fragile structure hinder their development. Herein, core-shell-like nickel-cobalt oxysulfide (NCOS) nanowires are synthesized and demonstrated as an advanced SICs anode. The bimetallic oxysulfide with multiple cation valence can promote the sodium ion adsorption and redox reaction, massive defects enable accommodation of the volume change in the sodiation/desodiation process, meanwhile the core-shell-like structure provides abundant channels for fast transfer of sodium ions, thereby synergistically making the NCOS electrode exhibit a high reversible sodium ion storage capacity (1468.5 mAh g^-1 at 0.1 A g^-1) and an excellent cyclability (90.5% capacity retention after 1000 cycles). The in-situ X-ray diffraction analysis unravels the insertion and conversion mechanism for sodium storage in NCOS, and the enhanced capability of NCOS is further verified by the kinetic analysis and theoretical calculations. Finally, SICs consisting of the NCOS anode and a boron-nitrogen co-doped carbon nanotubes cathode deliver an energy density of 205.7 Wh kg^-1, a power density of 22.5 kW kg^-1, and an outstanding cycling lifespan. These results indicate an efficient strategy in designing a high-performance anode for sodium storage based on bimetallic dianion compounds

Venus’ light slab hinders its development of planetary-scale subduction

Terrestrial planet Venus has a similar size, mass, and bulk composition to Earth. Previous studies proposed that local plume-induced subduction existed on both early Earth and Venus, and this prototype subduction might initiate plate tectonics on Earth but not on Venus. In this study, we simulate the buoyancy of submerged slabs in a hypothesized 2-D thermo-metamorphic model. We analyze the thermal state of the slab, which is then used for calculating density in response to thermal and phase changes. The buoyancy of slab mantle lithosphere is primarily controlled by the temperatures and the buoyancy of slab crust is dominated by metamorphic phase changes. Difference in the eclogitization process contributes most to the slab buoyancy difference between Earth and Venus, which makes the subducted Venus’ slab consistently less dense than Earth’s. The greater chemical buoyancy on Venus, acting as a resistance to subduction, may have impeded the transition into self-sustained subduction and led to a different tectonic regime on Venus. This hypothesis may be further tested as more petrological data of Venus become available, which will further help to assess the impact of petro-tectonics on the planet’s habitability

Volcanic ash as a driver of enhanced organic carbon burial in the Cretaceous

Abstract On greater than million year timescales, carbon in the ocean-atmosphere-biosphere system is controlled by geologic inputs of CO2 through volcanic and metamorphic degassing. High atmospheric CO2 and warm climates in the Cretaceous have been attributed to enhanced volcanic emissions of CO2 through more rapid spreading at mid-ocean ridges and, in particular, to a global flare-up in continental arc volcanism. Here, we show that global flare-ups in continental arc magmatism also enhance the global flux of nutrients into the ocean through production of windblown ash. We show that up to 75% of Si, Fe and P is leached from windblown ash during and shortly after deposition, with soluble Si, Fe and P inputs from ash alone in the Cretaceous being higher than the combined input of dust and rivers today. Ash-derived nutrient inputs may have increased the efficiency of biological productivity and organic carbon preservation in the Cretaceous, possibly explaining why the carbon isotopic signature of Cretaceous seawater was high. Variations in volcanic activity, particularly continental arcs, have the potential of profoundly altering carbon cycling at the Earth’s surface by increasing inputs of CO2 and ash-borne nutrients, which together enhance biological productivity and burial of organic carbon, generating an abundance of hydrocarbon source rocks

Persistent Hypoxia with Intermittent Aggravation Causes Imbalance in Smad3/Myocardin-Related Transcription Factor Signaling with Consequent Endothelial Senescence and Pulmonary Arterial Remodeling

Loss of Smad3 and the consequent activation of myocardin-related transcription factor (MRTF) are associated with vascular pathologies. This study aimed to examine the impact of persistent hypoxia with intermittent aggravation (PI hypoxia) on cellular senescence and pulmonary arterial remodeling mediated by the Smad3/MRTF imbalance. We examined the effects of PI hypoxia on the Smad3/MRTF pathway and cellular senescence using human pulmonary artery endothelial cells (HPAECs) and in vivo studies in rats. The senescent degree was evaluated using β-galactosidase staining, p16 quantitation and the measurement of senescence-associated secretory phenotype. Structural data in the pathological analysis of pulmonary artery remodeling were collected. Compared to the control, HPAECs and pulmonary tissue from rats exposed to PI hypoxia showed a significantly higher senescent degree, lower expression of Smad3, and higher MRTF levels. The overexpression of Smad3 significantly mitigated HPAECs senescence in vitro. Further, treatment with CCG-203971, which inhibits MRTF, increased Smad3 levels and reduced β-galactosidase positive cells in rat lung tissue. This intervention also alleviated PI hypoxia-induced pathological changes, including remodeling indices of pulmonary arterial thickening, muscularization, and collagen formation. In conclusion, imbalanced Smad3/MRTF signaling is linked to PI hypoxia-induced senescence and pulmonary arterial remodeling, making it a potential therapeutic target for patients with sleep apnea and chronic obstructive pulmonary disease