•Type I IFN is implicated in SLE pathogenesis by multiple lines of evidence, including genetics and induction of SLE by IFN treatment.•Nucleic-acid sensing pathways influence the threshold of ...activation and triggering of type I IFN production.•Abnormalities in extracellular processing of DNA can enhance type I IFN production.•High type I IFN levels are associated with nephritis, mucocutaneous manifestations, and the presence of autoantibodies in SLE.•Anifrolumab, a monoclonal antibody that blocks the type I IFN receptor, has shown therapeutic benefit in SLE.
Type I interferon (IFN) is a primary pathogenic factor in systemic lupus erythematosus (SLE). Gain-of-function genetic variants in the type I IFN pathway have been associated with risk of disease. Common polygenic as well as rare monogenic influences on type I IFN have been demonstrated, supporting a complex genetic basis for high IFN in many SLE patients. Both SLE-associated autoantibodies and high type I IFN can be observed in the pre-disease state. Patients with SLE and evidence of high type I IFN have more active disease and a greater propensity to nephritis and other severe manifestations. Despite the well-established association between type I IFN and SLE, the specific triggers of type I IFN production, the mechanisms by which IFNs help perpetuate the cycle of autoreactive cells and autoantibody production are not completely clear. This review provides an updated overview of type I IFN in SLE pathogenesis, clinical manifestations, and current therapeutic strategies targeting this pathway.
Nickel carbenes are attracting attention for the development of more sustainable catalysts, among others, for cyclopropanation. Intramolecular trapping of a nickel carbene intermediate with an olefin ...incorporated in a P(CC)P Ni pincer complex had previously allowed the isolation of a nickelacyclobutane intermediate and a detailed characterization of its reactivity. Herein, we report the reactivity of related nickel pincer complexes bearing a ketone P(CO)P or an imine P(CN)P with diazoalkanes as the carbene precursor. The observed reactivity suggests, in both cases, the reaction of the transient nickel carbene with one of the phosphine arms to form phosphorus ylides that subsequently react with the unsaturated backbone. Density functional theory (DFT) calculations are used to shed light on the mechanisms of these reactions.
In the present work, we obtained density (ρ123), speed of sound (u 123), excess molar volume (V m123 E ), and deviation in isentropic compressibility (Δk s123) for ternary mixtures of {BMIMBF4 (x 1) ...+ acetic acid (x 2) + acetophenone (x 3)} (mixture 1), {BMIMBF4 (x 1) + propionic acid (x 2) + acetophenone (x 3)} (mixture 2), and {BMIMPF6 (x 1) + acetic acid (x 2) + acetophenone (x 3)} (mixture 3) at temperatures ranging between 293.15 and 333.15 K and at a pressure of 0.1 MPa. V m123 E and Δk s123 values of the ternary systems were modeled with 9 predictive (no estimated parameter) and 7 correlative terms, leading to a total of 63 evaluated models. Using a standardized deviation (σ), it was possible to estimate the optimal number of parameters in the correlation, which varied from 1 to 11. The average σ for V m123 E mixture 3 was about twice the values for mixtures 1 and 2, even using more parameters for the last mixtures. For Δk s123, σ is in the same range for the three mixtures, even though only one parameter is used in each temperature for mixture 1 and up to 11 are used in mixtures 2 and 3. These results indicate that nonideality qualitatively is in the order mixture 3 > mixture 2 > mixture 1.
Nickelacyclobutanes are mostly invoked as reactive intermediates in the reaction of nickel carbenes and olefins to yield cyclopropanes. Nevertheless, early work suggested that other decomposition ...routes such as β‐hydride elimination and even metathesis could be accessible. Herein, we report the isolation and characterization of a stable pentacoordinated nickelacyclobutane incorporated in a pincer complex. The coordination of different coligands to the nickelacyclobutane determines its selective decomposition along cyclopropanation, metathesis or apparent β‐hydride elimination pathways. DFT calculations shed light on the mechanism of these different pathways.
A pincer scaffold allows the isolation of a nickelacyclobutane and a detailed study of its reactivity. The cycle slowly undergoes an apparent beta‐elimination reaction in non‐polar solvents; exposure to additional ligands leads to selective ring cleavage along either the cyclopropanation or the olefin metathesis pathway. These results give insight into the divergent reactivity of metallacyclobutane intermediates.
Metal–ligand cooperation can facilitate the activation of chemical bonds, opening reaction pathways of interest for catalyst development. In this context, olefins occupying the central position of a ...diphosphine pincer ligand (PCCP) are emerging as reversible H atom acceptors, e.g., for H2 activation. Here, we report on the reactivity of nickel complexes of PCCP ligands with a terminal alkyne, for which two competing pathways are observed. First, cooperative and reversible C–H bond activation generates a Ni(II) alkyl/alkynyl complex as the kinetic product. Second, in the absence of a bulky substituent on the olefin, two alkyne molecules are incorporated in the ligand structure to form a conjugated triene bound to Ni(0). The mechanisms of these processes are studied by density functional theory calculations supported by experimental observations.
In this study, sand and granular activated carbon (GAC) biofilters were comparatively assessed as post-treatment technologies of secondary effluents, including the fate of 18 organic micropollutants ...(OMPs). To determine the contribution of adsorption and biotransformation in OMP removal, four reactors were operated (two biofilters (with biological activity) and two filters (without biological activity)). In addition, the influence of empty bed contact time (EBCT), ranging from 0.012 to 3.2d, and type of secondary effluent (anaerobic and aerobic) were evaluated. Organic matter, ammonium and nitrate were removed in both biofilters, being their adsorption higher on GAC than on sand. According to the behaviour exhibited, OMPs were classified in three different categories: I) biotransformation and high adsorption on GAC and sand (galaxolide, tonalide, celestolide and triclosan), II) biotransformation, high adsorption on GAC but low or null adsorption on sand (ibuprofen, naproxen, fluoxetine, erythromycin, roxythromycim, sulfamethoxazole, trimethoprim, bisphenol A, estrone, 17β-estradiol and 17α-ethinylestradiol), and, III) only adsorption on GAC (carbamazepine, diazepam and diclofenac). No influence of EBCT (in the range tested) and type of secondary effluent was observed in GAC reactors, whereas saturation and kinetic limitation of biotransformation were observed in sand reactors. Taking into account that most of the organic micropollutants studied (around 60%) fell into category II, biotransformation is crucial for the elimination of OMPs in sand biofilters.
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•OMP removal was comparatively assessed in sand and GAC biofilters.•The contribution of adsorption and biotransformation in OMP removal was identified.•The filtering material did not affect the biological activities in biofilters.•There is no direct correlation between EBCT and OMP removal in biofilters.•The type of secondary effluent determines the lifespan of filtering material.
This work assesses the ability of the Mattedi–Tavares–Castier (MTC) equation of state (EOS) in representing the liquid phase density, sound speed, and vapor pressure of linear alkanes (C6–C20). It is ...found that its deviations from experimental data for liquid phase density, liquid phase sound speed, and vapor pressure are similar to, yet slightly higher than, those of the PC-SAFT EOS for the same compounds. Using only experimental data points at reduced pressures smaller than 20 for parameter fitting, a condition observed in most commercial chemical processes, leads to smaller deviations from the experimental values. Adopting for the lattice cell volume the value of 15 cm3/mol, which is the molar volume of the methylene group in the lattice-based UNIQUAC model, all the adjustable MTC EOS parameters follow regular trends with respect to the number of carbon atoms in the linear alkane chains. These parameters could be fitted to empirical expressions. When used, they produce deviations in pure-component liquid phase density, liquid phase sound speed, and vapor pressure equal to 0.6, 2.8, and 9.8%, respectively. The results for binary mixtures are generally in good agreement with the experimental data.
Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as ...reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury.
We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L−1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals.
Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 OR: 2.56 (1.92–3.41); P<0.0001. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count OR 1.80 (1.50–2.17); P<0.0001 and higher absolute preoperative monocyte count OR 1.93 (1.12–3.30); P=0.017. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03).
Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury.
NCT01842568.
Context.
The Multi-site All-Sky CAmeRA (MASCARA) and bRing are both photometric ground-based instruments with multiple stations that rely on interline charge-coupled devices with wide-field lenses to ...monitor bright stars in the local sky for variability. MASCARA has already discovered several planets in the northern sky, which are among the brightest known transiting hot Jupiter systems.
Aims.
In this paper, we aim to characterize a transiting planetary candidate in the southern skies found in the combined MASCARA and bRing data sets of HD 85628, an A7V star of
V
= 8.2 mag at a distance 172 pc, to establish its planetary nature.
Methods.
The candidate was originally detected in data obtained jointly with the MASCARA and bRing instruments using a Box Least-Square search for transit events. Further photometry was taken by the 0.7 m Chilean-Hungarian Automated Telescope (CHAT), and radial velocity measurements with the Fiber Dual Echelle Optical Spectrograph on the European Southern Observatory 1.0 m Telescope. High-resolution spectra during a transit were taken with the CTIO high-resolution spectrometer (CHIRON) on the Small and Moderate Aperture Research Telescope System 1.5 m telescope to target the Doppler shadow of the candidate.
Results.
We confirm the existence of a hot Jupiter transiting the bright A7V star HD 85628, which we co-designate as MASCARA-4b and bRing-1b. It is in an orbit of 2.824 days, with an estimated planet radius of 1.53
−0.04
+0.07
R
Jup
and an estimated planet mass of 3.1 ± 0.9
M
Jup
, putting it well within the planetary regime. The CHAT observations show a partial transit, reducing the probability that the transit was around a faint background star. The CHIRON observations show a clear Doppler shadow, implying that the transiting object is in a retrograde orbit with |
λ
| =244.9
−3.6
+2.7
°. The planet orbits at a distance of 0.047 ± 0.004 AU from the star and has a zero-albedo equilibrium temperature of 2100 ± 100 K. In addition, we find that HD 85628 has a previously unreported stellar companion star in the
Gaia
DR2 data demonstrating common proper motion and parallax at 4.3′′ separation (projected separation ~740 AU), and with absolute magnitude consistent with being a K/M dwarf.
Conclusions.
MASCARA-4 b/bRing-1 b is the brightest transiting hot Jupiter known to date in a retrograde orbit. It further confirms that planets in near-polar and retrograde orbits are more common around early-type stars. Due to its high apparent brightness and short orbital period, the system is particularly well suited for further atmospheric characterization.
DS Tuc Ab is a Neptune-sized planet that orbits around a G star in the 45 Myr old Tucana-Horologium moving group. Here, we report the measurement of the sky-projected angle between the stellar spin ...axis and the planet's orbital axis, based on the observation of the Rossiter-McLaughlin effect during three separate planetary transits. The orbit appears to be well aligned with the equator of the host star, with a projected obliquity of . In addition to the distortions in the stellar absorption lines due to the transiting planet, we observed variations that we attribute to large starspots, with angular sizes of tens of degrees. The technique that we have developed for simultaneous modeling of starspots and the planet-induced distortions may be useful in other observations of planets around active stars.
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