Context. Transit spectroscopy is one of the most commonly used methods to characterize exoplanets’ atmospheres. From the ground, these observations are very challenging due to the terrestrial ...atmosphere and its intrinsic variations, but high-spectral-resolution observations overcome this difficulty by resolving the spectral lines and taking advantage of the different Doppler velocities of the Earth, the host star, and the exoplanet. Aims. We analyze the transmission spectrum around the Na I doublet at 589 nm of the extrasolar planet WASP-69b, a hot Jupiter orbiting a K-type star with a period of 3.868 days, and compare the analysis to that of the well-known hot Jupiter HD 189733b. We also present the analysis of the Rossiter-McLaughlin (RM) effect for WASP-69b. Methods. We observed two transits of WASP-69b with the High Accuracy Radial velocity Planet Searcher (HARPS-North) spectrograph (R = 115 000) at the Telescopio Nazionale Galileo (TNG). We perform a telluric contamination subtraction based on the comparison between the observed spectra and a telluric water model. Then, the common steps of the differential spectroscopy are followed to extract the transmission spectrum. The method is tested with archival transit data of the extensively studied exoplanet HD 189733b, obtained with the HARPS-South spectrograph at ESO 3.6 m telescope, and then applied to WASP-69b data. Results. For HD 189733b, we spectrally resolve the Na I doublet and measure line contrasts of 0.72 ± 0.05% (D2) and 0.51 ± 0.05% (D1), and full width half maximum (FWHM) values of 0.64 ± 0.04 Å (D2) and 0.60 ± 0.06 Å (D1), in agreement with previously published results. For WASP-69b only the contrast of the D2 line can be measured (5.8 ± 0.3%). This corresponds to a detection at the 5σ-level of excess absorption of 0.5 ± 0.1% in a passband of 1.5 Å. A net blueshift of ~ 0.04 Å is measured for HD 189733b and no shift is obtained for WASP-69b. By measuring the RM effect, we get an angular rotation of 0.24-0.01+0.02 rad/day and a sky-projected angle between the stellar rotation axis and the normal of orbit plane (λ) of 0.4-1.9+2.0° for WASP-69b. Similar results to those previously presented in the literature are obtained for the RM analysis of HD 189733b. Conclusions. Even if sodium features are clearly detected in the WASP-69b transmission spectrum, more transits are needed to fully characterize the line profiles and retrieve accurate atmospheric properties.
Mounting evidence has shown that periodontitis is associated with diabetes. However, a causal relationship remains to be determined. Recent studies reported that periodontitis may be associated with ...gut microbiota, which plays an important role in the development of diabetes. Therefore, we hypothesized that gut microbiota might mediate the link between periodontitis and diabetes. Periodontitis was induced by ligatures. Glycemic homeostasis was evaluated through fasting blood glucose (FBG), serum glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance test. Micro–computed tomography and hematoxylin and eosin staining were used to evaluate periodontal destruction. The gut microbiota was analyzed using 16S ribosomal RNA gene sequencing and bioinformatics. Serum endotoxin, interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-1β were measured to evaluate the systemic inflammation burden. We found that the levels of FBG, HbA1c, and glucose intolerance were higher in the periodontitis (PD) group than in the control (Con) group (P < 0.05). When periodontitis was eliminated, the FBG significantly decreased (P < 0.05). Several butyrate-producing bacteria were decreased in the gut microbiota of the PD group, including Lachnospiraceae_NK4A136_group, Eubacterium_fissicatena_group, Eubacterium_coprostanoligenes_group, and Ruminococcaceae_UCG-014 (P < 0.05), which were negatively correlated with serum HbA1c (P < 0.05). Subsequently, the gut microbiota was depleted using antibiotics or transplanted through cohousing. Compared with the PD group, the levels of HbA1c and glucose intolerance were decreased in the gut microbiota-depleted mice with periodontitis (PD + Abx) (P < 0.05), as well as the serum levels of endotoxin and IL-6 (P < 0.05). The serum levels of IL-6, TNF-α, and IL-1β in the PD + Abx group were higher than those of the Con group (P < 0.05). Antibiotics exerted a limited impact on the periodontal microbiota. When the PD mice were cohoused with healthy ones, the elevated FBG and HbA1c significantly recovered (P < 0.05), as well as the aforementioned butyrate producers (P < 0.05). Thus, within the limitations of this study, our data indicated that the gut microbiota may mediate the influence of periodontitis on prediabetes.
Ultra-hot Jupiters are emerging as a new class of exoplanets. Studying their chemical compositions and temperature structures will improve our understanding of their mass loss rate as well as their ...formation and evolution. We present the detection of ionized calcium in the two hottest giant exoplanets – KELT-9b and WASP-33b. By using transit datasets from CARMENES and HARPS-N observations, we achieved high-confidence-level detections of Ca II using the cross-correlation method. We further obtain the transmission spectra around the individual lines of the Ca II H&K doublet and the near-infrared triplet, and measure their line profiles. The Ca II H&K lines have an average line depth of 2.02 ± 0.17% (effective radius of 1.56 Rp) for WASP-33b and an average line depth of 0.78 ± 0.04% (effective radius of 1.47 Rp) for KELT-9b, which indicates that the absorptions are from very high upper-atmosphere layers close to the planetary Roche lobes. The observed Ca II lines are significantly deeper than the predicted values from the hydrostatic models. Such a discrepancy is probably a result of hydrodynamic outflow that transports a significant amount of Ca II into the upper atmosphere. The prominent Ca II detection with the lack of significant Ca I detection implies that calcium is mostly ionized in the upper atmospheres of the two planets.
Nonalcoholic fatty liver disease (NAFLD) is a common result of obesity and metabolic syndrome. Hepatocyte injury and metabolic disorders are hallmarks of NAFLD. Stimulator of interferon genes (STING) ...and its downstream factor interferon regulatory factor 3 (IRF3) trigger inflammatory reaction in response to the presence of cytosolic DNA. STING has recently been shown to play an important role in early alcoholic liver disease. However, little is known about the role of STING-IRF3 pathway in hepatocyte injury. Here, we aimed to examine the effect of STING-IRF3 pathway on hepatocyte metabolism, inflammation and apoptosis.
We examined the activation of the STING-IRF3 pathway, a high-fat diet (HFD)-induced obese mouse model, and determined the role of this pathway in a free fatty acid (FFA)-induced hepatocyte inflammatory response, injury, and dysfunction in L-O2 human liver cells.
STING and IRF3 were upregulated in livers of HFD-fed mice and in FFA-induced L-O2 cells. Knocking down either STING or IRF3 led to a significant reduction in FFA-induced hepatic inflammation and apoptosis, as evidenced by modulation of the nuclear factor κB (NF-κB) signaling pathway, inflammatory cytokines, and apoptotic signaling. Additionally, STING/IRF3 knockdown enhanced glycogen storage and alleviated lipid accumulation, which were found to be associated with increased expression of hepatic enzymes in glycolysis and lipid catabolism, and attenuated expression of hepatic enzymes in gluconeogenesis and lipid synthesis.
Our results suggest that the STING-IRF3 pathway promotes hepatocyte injury and dysfunction by inducing inflammation and apoptosis and by disturbing glucose and lipid metabolism. This pathway may be a novel therapeutic target for preventing NAFLD development and progression.
Summary
Dexmedetomidine might reduce delirium after cardiac surgery. We allocated 326 participants to an infusion of dexmedetomidine at a rate of 0.6 μg kg−1 for 10 min and then at 0.4 μg.kg−1.h−1 ...until the end of surgery; 326 control participants received comparable volumes of saline. We detected delirium in 98/652 (15%) participants during the first seven postoperative days: 47/326 after dexmedetomidine vs. 51/326 after placebo, p = 0.62, adjusted relative risk (95%CI) 0.86 (0.56–1.33), p = 0.51. Postoperative renal impairment (Kidney Disease Improving Global Outcomes stages 1, 2 and 3) was detected in 46, 9 and 2 participants after dexmedetomidine and 25, 7 and 4 control participants, p = 0.040. Intra‐operative dexmedetomidine infusion did not reduce the incidence of delirium after cardiac valve surgery but might impair renal function.
By means of dynamic plastic deformation (DPD) with high strain rates, a bulk nanostructured 316L austenitic stainless steel consisting of nano-sized grains embedded with bundles of nanometer-thick ...deformation twins was synthesized. The average transverse grain size is ∼33nm and the twin/matrix lamellar thickness is ∼20nm. The nano-twin bundles constitute ∼24% in volume. The nanostructured samples exhibit a high tensile strength of ∼1400MPa but a limited ductility with a uniform elongation of ∼2%. Subsequent thermal annealing of the as-DPD samples in a temperature range of 730–800°C led to a single-phased austenite structure consisting of static recrystallized (SRX) micro-sized grains embedded with remaining nano-twin bundles and nano-grains. The annealed DPD samples exhibit an enhanced strength–ductility synergy and much more enhanced work-hardening rates than the as-deformed samples. Work-hardening rates of the annealed DPD samples can be even higher than that of the original CG sample. Tensile ductility was found to increase almost linearly with the volume fraction of SRX grains. A combination of 1.0GPa tensile strength with an elongation-to-failure of ∼27% is achieved in the annealed DPD 316L stainless steel samples.
Metallic glasses have a very high strength, hardness and elastic limit. However, they rarely show tensile ductility at room temperature and are considered quasi-brittle materials. Although these ...amorphous metals are capable of shear flow, severe plastic instability sets in at the onset of plastic deformation, which seems to be exclusively localized in extremely narrow shear bands ∼10 nm in thickness. Using in situ tensile tests in a transmission electron microscope, we demonstrate radically different deformation behaviour for monolithic metallic-glass samples with dimensions of the order of 100 nm. Large tensile ductility in the range of 23-45% was observed, including significant uniform elongation and extensive necking or stable growth of the shear offset. This large plasticity in small-volume metallic-glass samples did not result from the branching/deflection of shear bands or nanocrystallization. These observations suggest that metallic glasses can plastically deform in a manner similar to their crystalline counterparts, via homogeneous and inhomogeneous flow without catastrophic failure. The sample-size effect discovered has implications for the application of metallic glasses in thin films and micro-devices, as well as for understanding the fundamental mechanical response of amorphous metals.
KRAS mutation, which occurs in ∼95% of pancreatic ductal adenocarcinoma (PDA), has been shown to program tumor metabolism. MCT4 is highly upregulated in a subset of PDA with a glycolytic gene ...expression program and poor survival. Models with high levels of MCT4 preferentially employ glycolytic metabolism. Selectively in such “addicted” models, MCT4 attenuation compromised glycolytic flux with compensatory induction of oxidative phosphorylation and scavenging of metabolites by macropinocytosis and autophagy. In spite of these adaptations, MCT4 depletion induced cell death characterized by elevated reactive oxygen species and metabolic crisis. Cell death induced by MCT4-depletion was augmented by inhibition of compensatory pathways. In xenograft models, MCT4 had a significant impact on tumor metabolism and was required for rapid tumor growth. Together, these findings illustrate the metabolic diversity of PDA described by MCT4, delineate pathways through which this lactate transporter supports cancer growth, and demonstrate that PDA can be rationally targeted based on metabolic addictions.
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•MCT4 is associated with glycolytic metabolism and poor-prognosis pancreatic cancer•In addicted models, MCT4 is required for maintenance of effective metabolic activity•Depletion of MCT4 induces compensatory metabolism to avert a metabolic crisis•Targeting MCT4 suppresses tumor growth and yields vulnerability to metabolic stress
In pancreatic cancer, many metabolic features are driven by KRAS mutation. Baek et al. report that the lactate transporter MCT4 is a critical determinant of disease prognosis and glycolytic metabolism. These findings demonstrate distinct metabolic subtypes of pancreatic cancer and delineate metabolic vulnerabilities associated with lactate export.
High resolution transit spectroscopy has proven to be a reliable technique for the characterization of the chemical composition of exoplanet atmospheres. Taking advantage of the broad spectral ...coverage of the CARMENES spectrograph, we initiated a survey aimed at characterizing a broad range of planetary systems. Here, we report our observations of three transits of GJ 3470 b with CARMENES in search of He (2
3
S) absorption. On one of the nights, the He
I
region was heavily contaminated by OH
−
telluric emission and, thus, it was not useful for our purposes. The remaining two nights had a very different signal-to-noise ratio (S/N) due to weather. They both indicate the presence of He (2
3
S) absorption in the transmission spectrum of GJ 3470 b, although a statistically valid detection can only be claimed for the night with higher S/N. For that night, we retrieved a 1.5 ± 0.3% absorption depth, translating into a
R
p
(
λ
)∕
R
p
= 1.15 ± 0.14 at this wavelength. Spectro-photometric light curves for this same night also indicate the presence of extra absorption during the planetary transit with a consistent absorption depth. The He (2
3
S) absorption is modeled in detail using a radiative transfer code, and the results of our modeling efforts are compared to the observations. We find that the mass-loss rate,
Ṁ
, is confined to a range of 3 × 10
10
g s
−1
for
T
= 6000 K to 10 × 10
10
g s
−1
for
T
= 9000 K. We discuss the physical mechanisms and implications of the He
I
detection in GJ 3470 b and put it in context as compared to similar detections and non-detections in other Neptune-size planets. We also present improved stellar and planetary parameter determinations based on our visible and near-infrared observations.
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