Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients ...with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.
In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤ 5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.
Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of > 2.79 μg/mL (area under the curve (AUC) = 0.681; 95% CI 0.632 to 0.731) and ATI concentration of < 3.15 U/mL (AUC = 0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p < 0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p = 0.002) were independent predictors of remission.
The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.
Most refractory high-entropy alloys (HEAs) are brittle and suffer from limited formability at ambient temperature. Previous studies imply that grain boundaries affect their fracture behavior, but ...quantitative studies on the fracture properties of body-centered-cubic HEAs are scarce. Here, using in situ micro-cantilever tests, we show that the fracture toughness of a bi-crystal HEA, Nb25Mo25Ta25W25, is one order of magnitude lower than that of single crystalline ones. Atom probe tomography of the bi-crystal HEA reveals element segregation and formation of oxides and nitrides at grain boundaries, suggesting that minimizing grain boundary segregation is critical to improving fracture properties in refractory HEAs.
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•Biochar-supported catalysts were developed from nitrates and hydroxides of Ni and Co.•Hydroxide-based metals were insoluble, hence were deposited on the catalyst surface.•Surface and ...pore catalytic activities were identified in hydrotreatment experiments.•Biochar-supported catalysts offered improvements over a commercial Ni/C.
Biochar-supported catalysts were developed from nickel (Ni) - and cobalt (Co)- nitrates and hydroxides and tested for the hydrotreatment of carinata oil. Nitrate-based (from water-soluble salts) and hydroxide-based (from water-insoluble salts) catalysts of Ni and Co were prepared via wetness impregnation and aqueous dispersion methods, respectively. The catalysts were characterized using various tools such as, confocal XRF, BET specific surface area analyzer, NH3-TPD, and SEM-EDS. Synchroton method showed nitrate-sourced metals were dispersed mostly in the pores while, the hydroxide-sourced metals were distributed mainly on the catalyst surface. C = C saturation and cracking of triglycerides, decarboxylation, and hydrogenation of aromatic structures appeared to be dominant on the hydroxides of transition metals, hence took place on catalyst surface. Methanation and dehydrogenation (thus aromatization), however, seemed to be a pore phenomenon, catalyzed more over nitrate-based catalysts. A reaction network was proposed based on chemical analysis of upgraded carinata oil and erucic acid model compound. Catalytic cracking followed by hydrotreatment performed better in terms of fuel properties than other approaches in this study.
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). ...However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of epidermal growth factor receptor and extracellular-signal regulated kinase, which were required for induction of IL-25, IL-33, and TSLP expression. In two AD models, Itln knockdown suppressed expression of Il-33, Tslp, and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of AD. We conclude that ITLN contributes to allergen-induced Il-25, Il-33, and Tslp expression in asthma and AD.
The nitrogen isotope ratio 14N/15N is a powerful tool to trace Galactic stellar nucleosynthesis and constrain Galactic chemical evolution. Previous observations have found lower 14N/15N ratios in the ...Galactic center and higher values in the Galactic disk. This is consistent with the inside-out formation scenario of our Milky Way. However, previous studies mostly utilized double isotope ratios also including 12C/13C, which introduces additional uncertainties. Here we present observations of C14N and its rare isotopologue, C15N, toward a sample of star-forming regions measured by the IRAM 30 m and/or the ARO 12 m telescope at λ ∼ 3 mm wavelength. For those 35 sources detected in both isotopologues, physical parameters are determined. Furthermore, we have obtained nitrogen isotope ratios using the strongest hyperfine components of CN and C15N. For those sources showing small deviations from local thermodynamical equilibrium and/or self-absorption, the weakest hyperfine component, likely free of the latter effect, was used to obtain reliable 14N/15N values. Our measured 14N/15N isotope ratios from C14N and C15N measurements are compatible with those from our earlier measurements of NH3 and 15NH3 (Paper I), i.e., increasing ratios to a Galactocentric distance of ∼9 kpc. The unweighted second-order polynomial fit yields C14NC15N=(−4.85±1.89)kpc−2×RGC2+(82.11±31.93)kpc−1×RGC−(28.12±126.62). Toward the outer galaxy, the isotope ratio tends to decrease, supporting an earlier finding by H13CN/HC15N. Galactic chemical evolution models are consistent with our measurements of the 14N/15N isotope ratio, i.e., a rising trend from the Galactic center region to approximately 9 kpc, followed by a decreasing trend with increasing RGC toward the outer Galaxy.
Improved surface characteristics and incorporated Fe, S, and Cl species are reported in Fe-modified biochar, which makes it a prospective material for Hg(II) removal. In this study, aqueous Hg(II) ...was removed from solution by unmodified, FeCl3-modified, and FeSO4-modified biochars pyrolyzed at 300, 600, or 900 °C. Higher pyrolytic temperature resulted in higher removal efficiency, with the biochars pyrolyzed at 900 °C removing >96% of Hg(II). Fe-modification enhanced Hg(II) removal for biochars pyrolyzed at 600 °C (from 88% to >95%) or 900 °C (from 96% to 99%). Based on synchronous extended X-ray absorption fine structure (EXAFS) analysis, Hg coordinated to S in modified and unmodified biochars pyrolyzed at 900 °C, where thiol was reported, and in FeSO4-modified biochars pyrolyzed at 600 or 900 °C, where sulfide was recognized; in other biochars, Hg bound to O or Cl. Additionally, confocal micro-X-ray fluorescence imaging (CMXRFI) demonstrated Hg was distributed in agreement with S in biochars where HgS was formed; otherwise, Hg distribution was influenced by Hg species in solution and the pore characteristics of the biochar. This investigation provides information on the effectiveness and mechanisms of Hg removal that is critical for evaluating biochar applications and optimizing modification methods in groundwater remediation.
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•Fe modification improved Hg removal ability of biochar pyrolyzed at 600 or 900 °C.•HgS was formed in biochar with thiol or sulfide species.•Hg distributed corresponding to S in biochar with thiol or sulfide species.•Hg was adsorbed to biochar matrix or Fe oxides at the absence of thiol or sulfide.•HgO or HgCl was formed in consistent with Hg species in solution.
Lepidotrigona flavibasis
Cockerell, a eusocial bee species, performs a variety of ecological roles in tropical and subtropical ecosystems. This is the first study to evaluate the abiotic effects on ...the flight activity (exit, exit with garbage, entry, entry with resin, and entry with pollen) of
L. flavibasis
in the non-native habitat in Hainan province, China. The results showed that the colonies remained active throughout the year, peaking in January for the year and at 11:00 h for the day, respectively.
L. flavibasis
presented the greatest flight activities in the dry season. All flight activities of
L. flavibasis
were influenced by temperature and relative humidity. The ambient temperature or relative humidity had a significantly negative influence on flight activity of
L. flavibasis
. The maximum and minimum temperatures for
L. flavibasis
activity were recorded at 38 °C and 15 °C, respectively. Understanding the flight activities of
L. flavibasis
will be helpful for the better maintenance of colonies and improving meliponiculture. The results obtained here can provide information for the future development of techniques for
L. flavibasis
management and natural or artificial feeding.
Summary
Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.
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