Sulfur dioxide in the mid-infrared transmission spectrum of WASP-39b.

The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1-3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1-10 ppm)4-9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 µm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 µm in the 5-12-µm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5-25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 µm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1-8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.

A reflective, metal-rich atmosphere for GJ 1214b from its JWST phase curve.

There are no planets intermediate in size between Earth and Neptune in our Solar System, yet these objects are found around a substantial fraction of other stars1. Population statistics show that close-in planets in this size range bifurcate into two classes on the basis of their radii2,3. It is proposed that the group with larger radii (referred to as 'sub-Neptunes') is distinguished by having hydrogen-dominated atmospheres that are a few percent of the total mass of the planets4. GJ 1214b is an archetype sub-Neptune that has been observed extensively using transmission spectroscopy to test this hypothesis5-14. However, the measured spectra are featureless, and thus inconclusive, due to the presence of high-altitude aerosols in the planet's atmosphere. Here we report a spectroscopic thermal phase curve of GJ 1214b obtained with the James Webb Space Telescope (JWST) in the mid-infrared. The dayside and nightside spectra (average brightness temperatures of 553 ± 9 and 437 ± 19 K, respectively) each show more than 3σ evidence of absorption features, with H2O as the most likely cause in both. The measured global thermal emission implies that GJ 1214b's Bond albedo is 0.51 ± 0.06. Comparison between the spectroscopic phase curve data and three-dimensional models of GJ 1214b reveal a planet with a high metallicity atmosphere blanketed by a thick and highly reflective layer of clouds or haze.

Early Release Science of the exoplanet WASP-39b with JWST NIRISS.

The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy1-4. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality5-9. Here we present the transmission spectrum of WASP-39b obtained using the Single-Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument on the JWST. This spectrum spans 0.6-2.8 µm in wavelength and shows several water-absorption bands, the potassium resonance doublet and signatures of clouds. The precision and broad wavelength coverage of NIRISS/SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favouring a heavy-element enhancement ('metallicity') of about 10-30 times the solar value, a sub-solar carbon-to-oxygen (C/O) ratio and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are also best explained by wavelength-dependent, non-grey clouds with inhomogeneous coverageof the planet's terminator.

Early Release Science of the exoplanet WASP-39b with JWST NIRCam.

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy (for example, refs. 1,2) provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution and high precision, which, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0-4.0 micrometres, exhibit minimal systematics and reveal well defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous water in the atmosphere and place an upper limit on the abundance of methane. The otherwise prominent carbon dioxide feature at 2.8 micrometres is largely masked by water. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100-times solar (that is, an enrichment of elements heavier than helium relative to the Sun) and a substellar C/O ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation (for example, refs. 3,4,) or disequilibrium processes in the upper atmosphere (for example, refs. 5,6).

Photochemically produced SO2 in the atmosphere of WASP-39b.

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 µm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-µm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.

Publisher Correction: A planet within the debris disk around the pre-main-sequence star AU Microscopii.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A planet within the debris disk around the pre-main-sequence star AU Microscopii.

AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years1. AU Mic possesses a relatively rare2 and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star4, and with clumps exhibiting non-Keplerian motion5-7. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic 'activity' on the star8,9. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.

Mechanical regulation of breast cancer migration and apoptosis via direct and indirect osteocyte signaling.

Bone metastases, the migration of cancers to bone, occur in 65-80% of patients with advanced breast cancer. Metastasized cancer cells interact with cells such as the bone-resorbing osteoclasts to alter bone remodeling. Exercise, often suggested as an intervention for cancer patients, regulates bone remodeling via osteocytes. Osteocytes also signal to endothelial cells, which may affect cancer cell extravasation. Therefore, we hypothesize that mechanically stimulated osteocytes can regulate processes in breast cancer bone metastasis. To test this, we exposed osteocytes to oscillatory fluid flow in vitro using parallel-plate flow chambers. We observed that conditioned medium from flow-stimulated osteocytes increased migration (by 45%) and reduced apoptosis (by 12%) of breast cancer cells. Conditioned medium from osteoclasts conditioned in flowed osteocytes' conditioned medium reduced migration (by 47%) and increased apoptosis (by 55%) of cancer cells. Cancer cell trans-endothelial migration was reduced by 34% toward flowed osteocytes' conditioned medium. This difference was abolished with ICAM-1 or IL-6 neutralizing antibodies. Conditioned medium from endothelial cells conditioned in flowed osteocytes' conditioned medium increased cancer cell apoptosis by 29%. To summarize, this study demonstrated mechanically stimulated osteocytes' potential to affect breast cancer cells not only through direct signaling, but also through osteoclasts and endothelial cells. The anti-metastatic potential of the indirect signalings is particularly exciting since osteocytes are further away from metastasizing cancer cells than osteoclasts and endothelial cells. Future studies into the effect of bone mechanical loading on metastases and its mechanism will assist in designing cancer intervention programs that lowers the risk for bone metastases.

Ibuprofen/acetaminophen fixed-dose combination as an alternative to opioids in management of common pain types.

Opioids are frequently used first line to manage acute pain in a variety of settings; however, the use of nonprescription analgesics for acute pain is recognized by experts as a practical and effective opioid-sparing strategy. Variations in dosages and formulations and a lack of standardization in reporting clinical data hinder the awareness of nonprescription treatments and recommendation of their use before opioids and other prescription options. A fixed-dose combination (FDC) of two common nonprescription analgesics, ibuprofen (IBU) and acetaminophen (APAP), is an appealing alternative to opioids in acute pain settings with a range of potential benefits. This narrative review evaluates the evidence in support of IBU/APAP FDCs containing IBU (≤1200 mg/day) and APAP (≤4000 mg/day), the nonprescription maximum daily doses in Canada and the United States, as alternatives to opioids and as a means to reduce the need for rescue opioid medication in acute pain management. A literature search was performed to identify clinical studies that directly compared IBU/APAP FDCs with opioids or nonopioids and measured the need for opioid rescue therapy in acute pain. Across studies, IBU/APAP FDCs consistently demonstrated pain relief similar to or better than opioid and nonopioid comparators and reliably reduced the use of rescue opioids with fewer adverse events. Based on these data, healthcare clinicians should consider FDC nonprescription analgesics as a potential first-line option for the management of acute pain.

The growing trend of opioid-sparing treatment demands effective nonopioid pain management solutions. A fixed-dose combination (FDC) of ibuprofen and acetaminophen (IBU/APAP) has shown promise as an alternative to opioids in a range of pain management scenarios, but the available data are limited and can be difficult to compare across studies. In this review, the authors performed a comprehensive evaluation of the clinical studies that assessed the use of IBU/APAP FDCs as a means to prevent or decrease the use of opioids for patients with acute pain. In the included studies, IBU/APAP FDCs consistently and safely provided pain relief that could replace or reduce the need for opioids across a range of procedures. This manuscript can serve as a resource for healthcare clinicians when considering the use of IBU/APAP FDC treatments for acute pain management.

Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b.

Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 µm to 12 µm with the JWST's Mid-Infrared Instrument. The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet's nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.

Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice.

BACKGROUND & AIMS: Obesity-related insulin resistance contributes to cardiovascular disease. Cannabinoid receptor-1 (CB(1)) blockade improves insulin sensitivity in obese animals and people, suggesting endocannabinoid involvement. We explored the role of hepatic CB(1) in insulin resistance and inhibition of insulin signaling pathways. METHODS: Wild-type mice and mice with disruption of CB(1) (CB(1)(-/-) mice) or with hepatocyte-specific deletion or transgenic overexpression of CB(1) were maintained on regular chow or a high-fat diet (HFD) to induce obesity and insulin resistance. Hyperinsulinemic-euglycemic clamp analysis was used to analyze the role of the liver and hepatic CB(1) in HFD-induced insulin resistance. The cellular mechanisms of insulin resistance were analyzed in mouse and human isolated hepatocytes using small interfering or short hairpin RNAs and lentiviral knockdown of gene expression. RESULTS: The HFD induced hepatic insulin resistance in wild-type mice, but not in CB(1)(-/-) mice or mice with hepatocyte-specific deletion of CB(1). CB(1)(-/-) mice that overexpressed CB(1) specifically in hepatocytes became hyperinsulinemic as a result of reduced insulin clearance due to down-regulation of the insulin-degrading enzyme. However, they had increased hepatic glucose production due to increased glycogenolysis, indicating hepatic insulin resistance; this was further increased by the HFD. In mice with hepatocytes that express CB(1), the HFD or CB(1) activation induced the endoplasmic reticulum stress response via activation of the Bip-PERK-eIF2α protein translation pathway. In hepatocytes isolated from human or mouse liver, CB(1) activation caused endoplasmic reticulum stress-dependent suppression of insulin-induced phosphorylation of akt-2 via phosphorylation of IRS1 at serine-307 and by inducing the expression of the serine and threonine phosphatase Phlpp1. Expression of CB(1) was up-regulated in samples from patients with nonalcoholic fatty liver disease. CONCLUSIONS: Endocannabinoids contribute to diet-induced insulin resistance in mice via hepatic CB(1)-mediated inhibition of insulin signaling and clearance.

Recombinant erythroid Kruppel-like factor fused to GATA1 up-regulates delta- and gamma-globin expression in erythroid cells.

The ß-hemoglobinopathies sickle cell disease and ß-thalassemia are among the most common human genetic disorders worldwide. Hemoglobin A2 (HbA2, α2δ2) and fetal hemoglobin (HbF, α2γ2) both inhibit the polymerization of hemoglobin S, which results in erythrocyte sickling. Expression of erythroid Kruppel-like factor (EKLF) and GATA1 is critical for transitioning hemoglobin from HbF to hemoglobin A (HbA, α2ß2) and HbA2. The lower levels of δ-globin expression compared with ß-globin expression seen in adulthood are likely due to the absence of an EKLF-binding motif in the δ-globin proximal promoter. In an effort to up-regulate δ-globin to increase HbA2 expression, we created a series of EKLF-GATA1 fusion constructs composed of the transactivation domain of EKLF and the DNA-binding domain of GATA1, and then tested their effects on hemoglobin expression. EKLF-GATA1 fusion proteins activated δ-, γ-, and ß-globin promoters in K562 cells, and significantly up-regulated δ- and γ-globin RNA transcript and protein expression in K562 and/or CD34(+) cells. The binding of EKLF-GATA1 fusion proteins at the GATA1 consensus site in the δ-globin promoter was confirmed by chromatin immunoprecipitation assay. Our studies demonstrate that EKLF-GATA1 fusion proteins can enhance δ-globin expression through interaction with the δ-globin promoter, and may represent a new genetic therapeutic approach to ß-hemoglobinopathies.

A bimodal distribution of haze in Pluto's atmosphere.

Pluto, Titan, and Triton make up a unique class of solar system bodies, with icy surfaces and chemically reducing atmospheres rich in organic photochemistry and haze formation. Hazes play important roles in these atmospheres, with physical and chemical processes highly dependent on particle sizes, but the haze size distribution in reducing atmospheres is currently poorly understood. Here we report observational evidence that Pluto's haze particles are bimodally distributed, which successfully reproduces the full phase scattering observations from New Horizons. Combined with previous simulations of Titan's haze, this result suggests that haze particles in reducing atmospheres undergo rapid shape change near pressure levels ~0.5 Pa and favors a photochemical rather than a dynamical origin for the formation of Titan's detached haze. It also demonstrates that both oxidizing and reducing atmospheres can produce multi-modal hazes, and encourages reanalysis of observations of hazes on Titan and Triton.

The Venusian Lower Atmosphere Haze as a Depot for Desiccated Microbial Life: A Proposed Life Cycle for Persistence of the Venusian Aerial Biosphere.

We revisit the hypothesis that there is life in the venusian clouds to propose a life cycle that resolves the conundrum of how life can persist aloft for hundreds of millions to billions of years. Most discussions of an aerial biosphere in the venusian atmosphere temperate layers never address whether the life-small microbial-type particles-is free floating or confined to the liquid environment inside cloud droplets. We argue that life must reside inside liquid droplets such that it will be protected from a fatal net loss of liquid to the atmosphere, an unavoidable problem for any free-floating microbial life forms. However, the droplet habitat poses a lifetime limitation: Droplets inexorably grow (over a few months) to large enough sizes that are forced by gravity to settle downward to hotter, uninhabitable layers of the venusian atmosphere. (Droplet fragmentation-which would reduce particle size-does not occur in venusian atmosphere conditions.) We propose for the first time that the only way life can survive indefinitely is with a life cycle that involves microbial life drying out as liquid droplets evaporate during settling, with the small desiccated "spores" halting at, and partially populating, the venusian atmosphere stagnant lower haze layer (33-48 km altitude). We, thus, call the venusian lower haze layer a "depot" for desiccated microbial life. The spores eventually return to the cloud layer by upward diffusion caused by mixing induced by gravity waves, act as cloud condensation nuclei, and rehydrate for a continued life cycle. We also review the challenges for life in the extremely harsh conditions of the venusian atmosphere, refuting the notion that the "habitable" cloud layer has an analogy in any terrestrial environment.

Personalized antiplatelet therapy based on clopidogrel/aspirin resistance tests in acute ischemic stroke and transient ischemic attack: Study protocol of a multi-center, single-blinded and randomized controlled trial.

BACKGROUND: Clopidogrel and aspirin are key intervention for acute ischemic stroke (AIS) and transient ischemic attack (TIA). However, with increased clinical application, many patients have shown clopidogrel resistance (CR) and/or aspirin resistance (AR) that affect antiplatelet therapy on AIS/TIA. At present, there is no research reported on personalized antiplatelet therapy guidelines for patients with CR and/or AR. Our study aims to assess the effect of personalized antiplatelet therapy based on CYP2C19 genotype and urine 11-dhTxB2 tests in patients with AIS or TIA. METHODS: This is a multi-center randomized controlled trial. Eligible patients with AIS/TIA from 14 comprehensive hospitals in Jiangxi province will be recruited after obtaining informed consent. Participants will be randomly divided into the intervention group and the control group at a ratio of 1:1. personalized antiplatelet therapy based on the CYP2C19 genotype/urine11-dhTxB2 tests will be given to the intervention group. Demographics, disease history, laboratory investigations, therapys, physiological tests, imaging reports and other clinical features will be collected. Clinical outcomes including stroke recurrence, Modified Rankin Scale (mRS) score, bleeding events and all-cause mortality will be assessed at the 1st, 3rd, 6th, and 12th-month post-discharge. DISCUSSION: Our study will conduct free antiplatelet resistance tests and personalized antiplatelet therapy for AIS/TIA patients with CR/AR, ultimately evaluating personalized therapy effectiveness through one-year follow-up. The research results will help to assess the impact of personalized antiplatelet therapy on the prognosis of stroke, thus providing reference for precise clinical treatment.

Recent Advances in Understanding the Complexity of Alcohol-Induced Pancreatic Dysfunction and Pancreatitis Development.

Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.

Methane on Mars and Habitability: Challenges and Responses.

Recent measurements of methane (CH4) by the Mars Science Laboratory (MSL) now confront us with robust data that demand interpretation. Thus far, the MSL data have revealed a baseline level of CH4 (∼0.4 parts per billion by volume [ppbv]), with seasonal variations, as well as greatly enhanced spikes of CH4 with peak abundances of ∼7 ppbv. What do these CH4 revelations with drastically different abundances and temporal signatures represent in terms of interior geochemical processes, or is martian CH4 a biosignature? Discerning how CH4 generation occurs on Mars may shed light on the potential habitability of Mars. There is no evidence of life on the surface of Mars today, but microbes might reside beneath the surface. In this case, the carbon flux represented by CH4 would serve as a link between a putative subterranean biosphere on Mars and what we can measure above the surface. Alternatively, CH4 records modern geochemical activity. Here we ask the fundamental question: how active is Mars, geochemically and/or biologically? In this article, we examine geological, geochemical, and biogeochemical processes related to our overarching question. The martian atmosphere and surface are an overwhelmingly oxidizing environment, and life requires pairing of electron donors and electron acceptors, that is, redox gradients, as an essential source of energy. Therefore, a fundamental and critical question regarding the possibility of life on Mars is, "Where can we find redox gradients as energy sources for life on Mars?" Hence, regardless of the pathway that generates CH4 on Mars, the presence of CH4, a reduced species in an oxidant-rich environment, suggests the possibility of redox gradients supporting life and habitability on Mars. Recent missions such as ExoMars Trace Gas Orbiter may provide mapping of the global distribution of CH4. To discriminate between abiotic and biotic sources of CH4 on Mars, future studies should use a series of diagnostic geochemical analyses, preferably performed below the ground or at the ground/atmosphere interface, including measurements of CH4 isotopes, methane/ethane ratios, H2 gas concentration, and species such as acetic acid. Advances in the fields of Mars exploration and instrumentation will be driven, augmented, and supported by an improved understanding of atmospheric chemistry and dynamics, deep subsurface biogeochemistry, astrobiology, planetary geology, and geophysics. Future Mars exploration programs will have to expand the integration of complementary areas of expertise to generate synergistic and innovative ideas to realize breakthroughs in advancing our understanding of the potential of life and habitable conditions having existed on Mars. In this spirit, we conducted a set of interdisciplinary workshops. From this series has emerged a vision of technological, theoretical, and methodological innovations to explore the martian subsurface and to enhance spatial tracking of key volatiles, such as CH4.

Nitrogen Oxides in Early Earth's Atmosphere as Electron Acceptors for Life's Emergence.

We quantify the amount of nitrogen oxides (NOx) produced through lightning and photochemical processes in the Hadean atmosphere to be available in the Hadean ocean for the emergence of life. Atmospherically generated nitrate (NO3-) and nitrite (NO2-) are the most attractive high-potential electron acceptors for pulling and enabling crucial redox reactions of autotrophic metabolic pathways at submarine alkaline hydrothermal vents. The Hadean atmosphere, dominated by CO2 and N2, will produce nitric oxide (NO) when shocked by lightning. Photochemical reactions involving NO and H2O vapor will then produce acids such as HNO, HNO2, HNO3, and HO2NO2 that rain into the ocean. There, they dissociate into or react to form nitrate and nitrite. We present new calculations based on a novel combination of early-Earth global climate model and photochemical modeling, and we predict the flux of NOx to the Hadean ocean. In our 0.1-, 1-, and 10-bar pCO2 models, we calculate the NOx delivery to be 2.4 × 105, 6.5 × 108, and 1.9 × 108 molecules cm-2 s-1. After only tens of thousands to tens of millions of years, these NOx fluxes are expected to produce sufficient (micromolar) ocean concentrations of high-potential electron acceptors for the emergence of life. Key Words: Nitrogen oxides-Nitrate-Nitrite-Photochemistry-Lightning-Emergence of life. Astrobiology 17, 975-983.

Hypotheses for Near-Surface Exchange of Methane on Mars.

UNLABELLED: The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ mol(-1) to explain the magnitude of the methane spikes, higher than existing laboratory measurements. The second scenario is that microorganisms convert organic matter in the soil to methane when they are in liquid solutions. This scenario does not require regolith adsorption but entails extant life on Mars. The third scenario is that deep subsurface aquifers produce the bursts of methane. Continued in situ measurements of methane and water, as well as laboratory studies of adsorption and deliquescence, will test these hypotheses and inform the existence of the near-surface reservoir and its exchange with the atmosphere. KEY WORDS: Mars-Methane-Astrobiology-Regolith. Astrobiology 16, 539-550.

Entecavir promotes CD34⁺ stem cell proliferation in the peripheral blood and liver of chronic hepatitis B and liver cirrhosis patients.

Entecavir (ETV) has been used for more than 2 decades in treating hepatitis B virus (HBV) infections. It has shown significant anti-HBV effect and has led to histological improvement in the liver of chronic hepatitis B (CHB) patients. In patients treated with ETV for over two years, reversal of cirrhosis to normal tissue has also been observed. However, the mechanisms of these tissue repairing or recovery processes are not yet clear. In order to determine the roles that bone marrow and liver stem/progenitor cells play in these processes, we evaluated the CD34⁺ and CD133⁺ stem/progenitor cells in peripheral blood from 292 patients and liver tissues from 43 patients who had received therapies with and without ETV. A significant increase in both CD34⁺ and CD133⁺ cells was found in CHB and cirrhosis patients compared to the healthy controls. In patients treated with ETV, CD34⁺ cells increased 2 and 4 fold in peripheral blood and liver tissues, respectively, while their CD4⁺ and CD8⁺ cells remained the same. On the other hand, CD133⁺ cells did not change or even slightly decreased with ETV treatment. Results from immunohistochemistry staining, real time RT-PCR, and the enzyme-linked immunosorbent assay also revealed the same level of CD34⁺ cell increase and CD133⁺ cell decrease (or no change) in ETV treated patients, compared to patients without ETV therapies. Liver functions in patients with ETV treatment improved in general, but one liver cirrhosis patient with high expression of CD133 in liver tissue developed hepatocellular carcinoma (HCC). In summary, ETV may have differential effects on various stem cell subtypes. ETV-activated stem cells in bone marrow and liver tissues may contribute to the recovery from injuries caused by HBV infection. They also contribute to the regeneration of normal tissue and the recovery of normal liver function. Meanwhile, ETV does not activate stem cells that may participate in the initiation of HCC.