Higher Steady-state Concentrations Research Articles

Comparative study of Fe(III)/peroxymonosulfate, Fe(III)/hydrogen peroxide and Fe(III)/peroxydisulfate systems modified by sinapic acid for micropollutants degradation

Sinapic acid (SA) as an environmentally friendly natural phenolic acid, has the properties of antioxidant because of containing –OH and –OCH3 on the benzene ring and it is safe. The Fe(III)/peroxymonosulfate (PMS) system modified by SA for enhancing micropollutant degradation had been studied, while weather SA could improve micropollutant degradation in other Fe(III)/oxidants systems was still unclear. The Fe(III)/hydrogen peroxide (H2O2) and Fe(III)/peroxydisulfate (PDS) systems modified by SA for micropollutants degradation were studied, the results indicated that SA could enhancing micropollutants degradation by accelerating the Fe(III)/Fe(II) cycle in both systems. In addition, the PMS, the H2O2 and the PDS systems were compared, and ten micropollutants commonly present in natural water were selected to evaluate the oxidation capacity of different systems. The PMS and PDS systems have higher oxidation degradation capacity for ten micropollutants than that of H2O2 system, attributed to the SO4•−, HO• and Fe(IV) all contributing to micropollutants degradation. However, in the H2O2 system, ten micropollutants degradation almost entirely relied on HO•. In the PMS and PDS systems, the SO4•− played a dominated role for micropollutants removal, attributed to its higher steady-state concentration than HO• and its higher second-order reaction rate with micropollutants than Fe(IV). Economic evaluation indicted that the H2O2 system was more cost-effective than the PMS and PDS systems for micropollutants removal. This was because the cost of H2O2 was lower than PMS and PDS, and concentration of Fe(III), oxidants and SA requirements in the H2O2 system were lower than that in the PMS and PDS systems. Overall, this study provided an economical and environmental-friendly method for the efficient treatment of harmful micropollutants in wastewater.

Revisiting the Electron Transfer Mechanisms in Ru(III)-Mediated Advanced Oxidation Processes with Peroxyacids and Ferrate(VI).

The potential of Ru(III)-mediated advanced oxidation processes has attracted attention due to the recyclable catalysis, high efficiency at circumneutral pHs, and robust resistance against background anions (e.g., phosphate). However, the reactive species in Ru(III)-peracetic acid (PAA) and Ru(III)-ferrate(VI) (FeO42-) systems have not been rigorously examined and were tentatively attributed to organic radicals (CH3C(O)O•/CH3C(O)OO•) and Fe(IV)/Ru(V), representing single electron transfer (SET) and double electron transfer (DET) mechanisms, respectively. Herein, the reaction mechanisms of both systems were investigated by chemical probes, stoichiometry, and electrochemical analysis, revealing different reaction pathways. The negligible contribution of hydroxyl (HO•) and organic (CH3C(O)O•/CH3C(O)OO•) radicals in the Ru(III)-PAA system clearly indicated a DET reaction via oxygen atom transfer (OAT) that produces Ru(V) as the only reactive species. Further, the Ru(III)-performic acid (PFA) system exhibited a similar OAT oxidation mechanism and efficiency. In contrast, the 1:2 stoichiometry and negligible Fe(IV) formation suggested the SET reaction between Ru(III) and ferrate(VI), generating Ru(IV), Ru(V), and Fe(V) as reactive species for micropollutant abatement. Despite the slower oxidation rate constant (kinetically modeled), Ru(V) could contribute comparably as Fe(V) to oxidation due to its higher steady-state concentration. These reaction mechanisms are distinctly different from the previous studies and provide new mechanistic insights into Ru chemistry and Ru(III)-based AOPs.

Cobalt(VI)-oxo species-mediated selective oxidation of electron-rich organic contaminants by Co-loaded hydroxylated g-C3N4 with high resistance to an inhibitory effect of background constituents

Understanding of the selectivity of high-valent cobalt-oxo species (Co(IV)O) toward diverse organic pollutants with different characteristics in the presence of background constituents remains limited. Here, we prepared Co-loaded hydroxyl group-grafted graphitic carbon nitride (Co-OHCN) using a facile method for the effective formation of Co(IV)O. The role of the hydroxyl group in anchoring Co ions was investigated using several characterization methods (TEM, XRD, FT-IR, and XPS). Co-OHCN exhibited superior efficiency in degrading 4-chlorophenol (4-CP) (98.0 % ± 0.3 %) within 15 min of peroxymonosulfate (PMS) activation reaction. In the Co-OHCN/PMS system, Co(IV)O had the highest steady-state concentration ([Co(IV)O] = 1.40 × 10−10 M), significantly exceeding that of other reactive oxygen species (ROS) ([SO4−] = 9.22 × 10−13 M, [OH] = 1.82 × 10−13 M). The dominant role of Co(IV)O in 4-CP degradation was further revealed through scavenger tests, probe methods, and electrochemical analysis. Additionally, the anti-interference of Co(IV)O in the degradation of electron-rich organic substrates to background constituents (NOM and halide ions) was systemically validated using three organic pollutants with different ionization potential values (diclofenac, 4-CP, and benzoic acid). This study provides insight into an efficient strategy for Co(IV)O -mediated pollutant elimination and organic substrate-dependent selectivity of Co(IV)O during water decontamination.

Dual role of dissolved black carbon in sensitized ofloxacin photooxidation: Mechanism and influential factors

Dissolved black carbon (DBC) is the more photoactive component of dissolved organic matter (DOM) pool, which plays a dual role in the photoconversion of aquatic contaminants, acting as both a photosensitizer and an inhibitor. However, little is known about the more systematic mechanism by which DBC exhibits a dual effect, which is closely related to the structure composition of DBC. In this study, the differences in characteristics of DBC obtained from 300 °C and 500 °C were compared via UV–vis absorption spectrum, Fluorescence excitation emission matrix spectra (3D-EEM), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS), and evaluated the promoting and inhibiting effects of DBC on ofloxacin (OFL) photodegradation. It was found that higher pyrolysis temperature reduced the UV absorbance, molecular weight, aromaticity, and phenolics of DBC while increasing the content of quinone/aromatic ketone and humic substances. Photochemical data showed that 3DBC*, 1O2 and ·OH were all participated in the DBC-mediated OFL photodegradation. Wherein, DBC300 (DBCT, where T = pyrolysis temperature) had strong light screening and dynamic quenching effect, but the formation ability of 3DBC*, 1O2 and ·OH was poor, which significantly retarded the photodegradation of OFL. While DBC500 exhibited a slight promotion effect due to its higher formation ability of reactive species and weak light screening effect. Moreover, DBC500 had higher steady-state concentration and (kOFL,3DBC⁎) than DBC300, which might be due to the higher contents of quinone/aromatic ketone and the lower contents of phenol in DBC500, thus enhancing the reactivity of 3DBC* and OFL. Our research systematically revealed the trade-off mechanism of DBC on the photodegradation of fluoroquinolones, and provided an important theoretical guidance for the photodegradation of fluoroquinolones under the evolution of DBC composition.

Photochemical fate of β-blocker pindolol in riverine and its downstream coastal waters

Pindolol (PIN) is a commonly used β-blocker drug and has been frequently detected in various natural waters. Comprehensive understanding of its environmental photochemical transformation is necessary to assess its environmental risk. In this study, the photodegradation kinetics and mechanisms of PIN in both freshwater and coastal water were investigated for the first time. The photodegradation experiments were carried out by steady-state photochemical experiment under simulated sunlight irradiation. The results showed that the photodegradation rate of PIN in the freshwater of the Pearl River estuary was significantly faster than that in its downstream coastal water. In river water, PIN can undergo both direct photolysis and indirect photolysis induced by riverine dissolved organic matter (DOM) mainly through excited triplet-state of DOM and singlet oxygen, while direct photolysis dominated its degradation in coastal water. The promotion effect was found to be much greater for Suwannee River Natural Organic Matter (SRNOM) than that of the sampled riverine DOM, due to its high steady-state concentrations of reactive species. Interestingly, coastal DOM in northern and southern China were found to have similar promotion effects on PIN photodegradation for the first time, but both less than that of riverine DOM. A total of seven degradation products of PIN resulting from hydroxylation, hydrogen abstraction and cleavage of ether bond were identified. Biological toxicity of one products were found to be higher than that of PIN. These results are of significance for knowing the persistence and ecological risk of PIN in natural waters.

Chlorine oxide radical (ClO[rad]) enables the enhanced degradation of antibiotic resistance genes during UV/chlorine treatment by selectively inducing base damage

Compared to individual UV or chlorine disinfection, the combined UV and chlorine (i.e., UV/chlorine) can substantially promote the degradation of antibiotic resistance genes (ARGs) in the effluent by generating radicals. However, the mechanisms of ARG degradation induced by radicals during UV/chlorine treatment remain largely unknown, limiting further enhancement of ARG degradation by process optimization. Herein, we aimed to uncover the role of different radicals in ARG degradation and the molecular mechanisms of ARG degradation by radicals in UV/chlorine process. The ClO was proven to be responsible for the enhanced ARG degradation during UV/chlorine treatment, while the other radicals (OH, Cl, and Cl2−) played a minor role. This is because ClO possessed both high steady-state concentration and high reactivity toward ARGs (rate constant: 4.29 × 1010 M−1 s−1). The ClO might collaborate with free chlorine to degrade ARG. The ClO degraded ARGs by selectively attacking guanine and thymine but failed to induce strand breakage, while chlorine could break the strand of ARGs. Ultimately, ClO cooperated with chlorine to degrade ARGs quickly by hydroxylation and chlorination of bases and produce many chlorine- and nitrogen-containing products as revealed by high-resolution mass spectrometry. The uncovered degradation mechanisms of ARGs by UV/chlorine provide useful guidelines for process optimization to achieve deep removal of effluent ARGs.

Hijacking the hydrogen atoms in photo-splitting of H2O2 for efficient reduction of CO2 to CH3OH

Photo-splitting of H2O2 in visible light is achieved by Cu-MOFs of Cu nodes and 1, 3, 5-benzene tricarboxylic acid (BTC) organic linkers (CuM) decorated with CdS (C) at varying concentrations of CdS in the CuMC composite. This process produces abundant nascent hydrogen atoms to promote the efficient catalytic reduction of CO2 to methanol (CH3OH) in visible light. The slow rate of recombination of the nascent hydrogen atoms produced by the H2O2 photo-splitting on the surface of the CdS quantum dots ensures a high steady-state concentration of hydrogen atoms with significantly reduced production of the less reactive hydrogen gas. With slow recombination of the photo-generated charges and the large surface areas for CO2 adsorption by the MOF, one of the CuMC composites is capable of convertingCO2 into CH3OH with a quantum efficiency approaching 80 %. A mechanism for the selective conversion of CO2 into CH3OH is proposed.

Photochemical degradation mechanisms and ecotoxicity of propranolol in natural water under simulated and natural sunlight irradiation

The widespread use of propranolol (PRO) has led to its detection in all types of natural water bodies, and it is hazardous to both aquatic organisms and humans. In this study, the photochemical transformation of PRO in the natural environment was investigated using both simulated and outdoor light experiments. The photodegradation of PRO was found to be faster in Pearl river water and the dissolved organic matter (DOM) solutions than that in pure water under sunlight irradiation. Quenching experiments show that the excited triplet states DOM (3DOM*) played a major role while ·OH and 1O2 played minor roles in PRO degradation. The secondary reaction rate constants of 3DOM* with PRO were determined to be (4.32 ∼ 6.38) × 108 M−1 s−1. DOM with high steady-state concentrations of the generated reactive species has higher photochemical reactivity for PRO photodegradation. Total of seven products were identified in in pure water, Pearl River water and three DOM solutions. The degradation of PRO can be mainly through hydroxyl addition, dehydration, naphthalene removal and isopropyl removal reactions. The reaction sites predicted by frontier electronic density calculations can further infer degradation pathways. The ecotoxicity of degradation products was found to be decreased relative to PRO through Ecological Structure Activity Relationship (ECOSAR) program.

Is the steady-state concentration, duration of action, or molecular weight of GLP-1RA associated with cardiovascular and renal outcomes in type 2 diabetes?

ImportanceDisparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear. ObjectiveTo assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). Data SourcesPubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022. Study SelectionRandomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included. Data Extraction And SynthesisLiterature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs. Main Outcomes and MeasuresPrimary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality. ResultsIn all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes. Conclusions and RelevanceGLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D.

A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.

Upgrading the peroxi-coagulation treatment of complex water matrices using a magnetically assembled mZVI/DSA anode: Insights into the importance of ClO radical.

The electrochemical technologies for water treatment have flourished over the last decades. However, it is still challenging to treat the actual complex water effluents by a single electrochemical process, often requiring coupling of technologies. In this study, an upgraded peroxi-coagulation (PC) process with a magnetically assembled mZVI/DSA anode has been devised for the first time. COD, NH3-N and total phosphorous were simultaneously and effectively removed from livestock wastewater. The advantages, influence of key parameters and evolution of electrogenerated species were systematically investigated to fully understand this novel PC process. The fluorescent substances in livestock wastewater could also be almost removed under optimal conditions (300mA, 0.2g ZVI particles and pH 6.8). The interaction between OH and active chlorine yielded ClO with a high steady-state concentration of 6.85×10-13M, which did not cause COD removal but accelerated the oxidation of NH3-N. The Mulliken population suggested that OH and NH3-N had similar electron-donor behavior, whereas ClO acted as an electron-withdrawing species. Besides, although the energy barrier for the reaction between OH and NH3-N (17.0kcal/mol) was lower than that with ClO (18.8kcal/mol), considering the tunneling in the H abstraction reaction, the Skodje-Truhlar method adopted for calculations evidenced a 17-fold faster NH3-N oxidation rate with ClO. In summary, this work describes an advantageous single electrochemical process for the effective treatment of a complex water matrix.

Baseline uric acid levels and steady-state favipiravir concentrations are associated with occurrence of hyperuricemia among COVID-19 patients

ObjectivesFavipiravir is an antiviral that is being evaluated for the treatment of COVID-19. Use of favipiravir is associated with elevation of serum uric acid levels. Risk factors for the occurrence of hyperuricemia are unclear. MethodsSpecimens from COVID-19 patients who received 10 days of favipiravir in a previous clinical trial (jRCTs041190120) were used. Serum favipiravir concentrations were measured by LC-MS. Factors associated with the development of hyperuricemia were investigated using logistic regression analysis. Optimal cut-off values for the baseline serum uric acid levels and steady-state serum favipiravir concentrations in predicting the occurrence of hyperuricemia were determined by ROC curve analysis. ResultsAmong the 66 COVID-19 patients who were treated with favipiravir for 10 days, the steady-state serum favipiravir concentrations were significantly correlated with serum uric acid levels. High baseline serum uric acid levels and steady-state serum favipiravir concentrations during therapy were factors associated with the development of hyperuricemia. The cut‑off baseline serum uric acid level and steady-state serum favipiravir concentration during favipiravir administration determined to predict hyperuricemia were 3.7 mg/dL and 46.14 μg/mL, respectively. ConclusionsPatients with high baseline serum uric acid levels or who achieved high steady-state serum favipiravir concentrations during therapy were susceptible to hyperuricemia.

CYP2C19 Genotyping May Provide a Better Treatment Strategy when Administering Escitalopram in Chinese Population.

Depression disorder is one of the most serious mental illnesses in the world. Escitalopram is the essential first-line medication for depression disorder. It is the substrate of hepatic cytochrome P450 (CYP) enzyme CYP2C19 with high polymorphism. The effect of CYP2C19 on pharmacokinetics and pharmacodynamics on Caucasian population has been studied. The Clinical Pharmacogenetics Implementation Consortium Guideline provides dosing recommendations for escitalopram on CYP2C19 genotypes on the basis of the studies on Caucasian population. However, the gene frequency of the alleles of CYP2C19 showed racial differences between Chinese and Caucasian populations. Representatively, the frequency of the *2 and *3 allele, which were considered as poor metabolizer, has been shown to be three times higher in Chinese than in Caucasians. In addition, the environments might also lead to different degrees of impacts on genotypes. Therefore, the guidelines based on the Caucasians may not be applicable to the Chinese, which induced the establishment of a guideline in China. It is necessary to provide the evidence of individual treatment of escitalopram in Chinese by studying the effect of CYP2C19 genotypes on the pharmacokinetics parameters and steady-state concentration on Chinese. In this study, single-center, randomized, open-label, two-period, two-treatment crossover studies were performed. Ninety healthy Chinese subjects finished the trials, and they were included in the statistical analysis. The pharmacokinetics characteristics of different genotypes in Chinese were obtained. The results indicate that the poor metabolizer had higher exposure, and increased half-life than the extensive metabolizer and intermediate metabolite. The prediction of steady-state concentration based on the single dose trial on escitalopram shows that the poor metabolizer might have a higher steady-state concentration than the extensive metabolizer and intermediate metabolite in Chinese. The results indicate that the genetic testing before medication and the adjustment of escitalopram in the poor metabolizer should be considered in the clinical treatments in Chinese. The results provide the evidence of individual treatment of escitalopram in Chinese, which will be beneficial for the safer and more effective application of escitalopram in the Chinese population.Clinical Trial Registration: identifier ChiCTR1900027226.

Surprisingly long lifetime of methacrolein oxide, an isoprene derived Criegee intermediate, under humid conditions

Ozonolysis of isoprene, the most abundant alkene, produces three distinct Criegee intermediates (CIs): CH2OO, methyl vinyl ketone oxide (MVKO) and methacrolein oxide (MACRO). The oxidation of SO2 by CIs is a potential source of H2SO4, an important precursor of aerosols. Here we investigated the UV-visible spectroscopy and reaction kinetics of thermalized MACRO. An extremely fast reaction of anti-MACRO with SO2 has been found, kSO2 = (1.5 ± 0.4) × 10−10 cm3 s−1 (±1σ, σ is the standard deviation of the data) at 298 K (150 − 500 Torr), which is ca. 4 times the value for syn-MVKO. However, the reaction of anti-MACRO with water vapor has been observed to be quite slow with an effective rate coefficient of (9 ± 5) × 10−17 cm3 s−1 (±1σ) at 298 K (300 to 500 Torr), which is smaller than current literature values by 1 or 2 orders of magnitude. Our results indicate that anti-MACRO has an atmospheric lifetime (best estimate ca. 18 ms at 298 K and RH = 70%) much longer than previously thought (ca. 0.3 or 3 ms), resulting in a much higher steady-state concentration. Owing to larger reaction rate coefficient, the impact of anti-MACRO on the oxidation of atmospheric SO2 would be substantial, even more than that of syn-MVKO.

Continuous infusion of cefepime and neurotoxicity: a retrospective cohort study

ObjectivesNeurotoxicity related to cefepime is increasingly reported in the literature but specific data concerning continuous infusion (CI) of the drug are still lacking. Our primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. Our secondary objectives were to analyse the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs. MethodsIn this single-centre retrospective cohort study, all adult patients who underwent at least one cefepime therapeutic drug monitoring (TDM) and were treated with CI of 4 g/day between January 2017 and June 2019 were included. Neurotoxicity was evaluated according to a strict definition and was correlated with steady-state concentration at the time of toxicity presentation. ResultsNinety-eight patients with 201 cefepime TDM studies were included, with an incidence of neurotoxicity of 14.3% (14/98). Patients with neurotoxicity had more often underlying brain disease (35.7% (5/14) vs 11.9% (10/84), p = 0.030)) and higher steady-state concentrations (mean ± standard deviation 71.8 ± 32.9 mg/L vs 49.6 ± 30.6, p = 0.036) than the others. A receiver operating characteristic curve analysis yielded a cefepime steady-state concentration of 63.2 mg/L as the best cut-off point between patients with or without neurotoxicity. A mean steady-state concentration of 46.4 mg/L was achieved if the dosages of cefepime were adapted to renal function which was under our threshold concentration but above our highest pharmacokinetic/pharmacodynamic target of 32–40 mg/L. ConclusionsOur results suggest that 4 g/day of cefepime adapted to renal function and infused over 24 h is a trade-off for the risk/benefit ratio, when used empirically.

Degradation of Acetaminophen via UVA-induced advanced oxidation processes (AOPs). Involvement of different radical species: HO[rad], SO4[rad]− and HO2[rad]/O2[rad

In this work, UVA radiation that is part of solar light is taken as the irradiation source and radicals (HO, SO4− and HO2/O2−) are generated through activation of hydrogen peroxide (H2O2), sodium persulfate (Na2S2O8) and Bismuth catalyst (BiOCl), respectively. The distinguished performance in removing acetaminophen (ACTP), a model pharmaceutical pollutant, by these three radicals was compared for the first time. Effect of pH, halide ions concentration and interfacial mechanism have been investigated in detail. Interestingly, results show that heterogeneous UVA/BiOCl process has higher degradation efficiency than homogeneous UVA/H2O2 and UVA/Na2S2O8 systems whatever the solution’s pH. To explain these results, second order reaction rate constant (kradical, ACTP) have been determined with laser flash photolysis (LFP) or radical scavenging experiments. The strongly interfacial-depended HO2/O2− radicals have the lowest second order rate constant with ACTP but highest steady state concentration. BiOCl is much easier activated by UVA, and outstanding ACTP mineralization can be achieved. Combination of BiOCl and Na2S2O8 exhibits synergistic effects rather than antagonism effects with H2O2. This study highlights the relative effective utilization of solar light through interfacial directed BiOCl photocatalysis and its synergistic effects with traditional oxidants.

Secondary organic aerosol formation from 3C⁎-initiated oxidation of 4-ethylguaiacol in atmospheric aqueous-phase

In this study, we investigated aqueous-phase triplet excited states (3C⁎)-induced photo-degradation of 4-ethylguaiacol (EG) under both simulated sunlight and ultraviolet (UV) light irradiations. Through quencher experiments, the relative contributions of reactive oxygen species (ROS, such as 1O2/O2−/·OH) and 3C⁎ were calculated and results showed three reactive species, e.g., 3C⁎, 1O2 and O2−, all seemed to play important roles in the photo-degradation of EG, but contribution from ·OH was relatively minor. High steady-state 1O2 concentration after 1 h irradiation further revealed the major contribution of 1O2 to photo-degradation under Xe light irradiation. The degradation experiment under three saturated gases (air, O2 and N2) showed that the degradation rate in air-saturated condition was the largest owing to synergistic effect of 1O2 and 3C⁎. Oxidative capacity of aqueous secondary organic aerosol (aqSOA) increased with reaction time by monitoring oxygen-to‑carbon (O/C) ratio and carbon oxidation state (OSc) via an aerodyne soot particle aerosol mass spectrometer (SP-AMS). Moreover, aqSOA mass yields were calculated via SP-AMS data. The UV–vis spectral change suggested formation of light-absorbing organics at first stage under simulated sunlight irradiation. Based on the identified products and the reactive intermediates, we postulated that 3C⁎-induced oxidation might be attributed to direct reactions by 3C⁎ and 1O2, chemical reaction by ROS, as well as oligomerization via H-abstraction. To the best of our knowledge, this is the first time to explore systematically reaction pathways of 4-ethylguaiacol under 3C∗ radical on the basis of thorough analysis of products and reactive species. Our findings highlight the impacts of aqSOA from biomass burning emissions on air quality and climate change.

Cytosolic Fe-superoxide dismutase safeguards Trypanosoma cruzi from macrophage-derived superoxide radical

Trypanosoma cruzi, the causative agent of Chagas disease (CD), contains exclusively Fe-dependent superoxide dismutases (Fe-SODs). During T. cruzi invasion to macrophages, superoxide radical (O2•-) is produced at the phagosomal compartment toward the internalized parasite via NOX-2 (gp91-phox) activation. In this work, T. cruzi cytosolic Fe-SODB overexpressers (pRIBOTEX-Fe-SODB) exhibited higher resistance to macrophage-dependent killing and enhanced intracellular proliferation compared with wild-type (WT) parasites. The higher infectivity of Fe-SODB overexpressers compared with WT parasites was lost in gp91-phox-/- macrophages, underscoring the role of O2•- in parasite killing. Herein, we studied the entrance of O2•- and its protonated form, perhydroxyl radical [(HO2•); pKa = 4.8], to T. cruzi at the phagosome compartment. At the acidic pH values of the phagosome lumen (pH 5.3 ± 0.1), high steady-state concentrations of O2•- and HO2• were estimated (∼28 and 8 µM, respectively). Phagosomal acidification was crucial for O2•- permeation, because inhibition of the macrophage H+-ATPase proton pump significantly decreased O2•- detection in the internalized parasite. Importantly, O2•- detection, aconitase inactivation, and peroxynitrite generation were lower in Fe-SODB than in WT parasites exposed to external fluxes of O2•- or during macrophage infections. Other mechanisms of O2•- entrance participate at neutral pH values, because the anion channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid decreased O2•- detection. Finally, parasitemia and tissue parasite burden in mice were higher in Fe-SODB-overexpressing parasites, supporting the role of the cytosolic O2•--catabolizing enzyme as a virulence factor for CD.

Administration of recombinant FVIIa (rFVIIa) to concizumab‐dosed monkeys is safe, and concizumab does not affect the potency of rFVIIa in hemophilic rabbits

Essentials Hemophilia patients on concizumab prophylaxis may need rFVIIa to treat breakthrough bleeds. Effect and safety of concizumab+rFVIIa were tested invitro and invivo. Concizumab+rFVIIa had no additive effects on bleeding in hemophilic rabbits. High steady-state levels of concizumab did not affect the safety of rFVIIa in cynomolgus monkeys. SUMMARY: Background Concizumab is a monoclonal antibody (mAb) against tissue factor pathway inhibitor (TFPI), currently in clinical development as a subcutaneous prophylactic therapy for hemophiliaA/B with and without inhibitors. In patients with inhibitors, the treatment choice for breakthrough bleeding will comprise bypassing agents, e.g. activated recombinant FVIIa (rFVIIa) or activated prothrombin complex concentrates. Objectives To explore the effect and safety of concizumab and rFVIIa when they are simultaneously present. Methods Human blood made hemophilic with a FVIII antibody was spiked with increasing concentrations of concizumab, rFVIIa, or concizumab and rFVIIa in combination, and this was followed by thrombin generation test or thromboelastography. Blood loss in hemophilic rabbits was measured when concizumab, rFVIIa or concizumab+rFVIIa was administered either before or during cuticle bleeding. In a safety study, cynomolgus monkeys were exposed to high steady-state concizumab concentrations and given three doses of rFVIIa, and then subjected to full necropsy and histopathological examination. Results In human blood, concizumab+rFVIIa had more pronounced procoagulant effects under hemophilic conditions than the sum of individual responses. In contrast, concizumab+rFVIIa had no additional effects on blood loss in hemophilic rabbits as compared with rFVIIa or concizumab alone. In cynomolgus monkeys, the macroscopic and microscopic pathological examinations revealed no thrombi or other signs of excessive coagulation activation. Both rFVIIa and concizumab caused increases in thrombin-antithrombin and D-dimer concentrations; this effect tended to be additive with concomitant administration. Conclusions Concizumab did not affect the potency or safety of rFVIIa invivo. These results support a clinical evaluation of rFVIIa at standard dose (90μgkg-1 ) to treat breakthrough bleeds in concizumab clinical trials.

Improving low-temperature CS2 conversion for the Claus process by using La(III)-doped nanofibrous TiO2 xerogel

Not only do the natural gas and petroleum industries face the challenge of stringent sulfur compound emission limits, but it is also important to use new technologies to reduce the carbon footprint and improve energy efficiency. Herein this research is aimed at developing a new generation of catalysts that can potentially decrease the reaction temperature of Claus catalytic converters (used to convert sulfur compounds to elemental sulfur), and also reduce the amount of catalyst. There are two factors that affect the performance of the conventional Claus catalysts. First, the conventional metal oxide catalysts suffer from ageing, trapped liquid sulfur fouling in the mesopores and high steady-state concentration of surface sulfate, which reduce the number of active sites for CS2 conversion. Therefore, the industry has to pay the price for a high reaction temperature to maintain a satisfactory CS2 conversion, while sacrificing Claus conversion (2H2S + SO2). Second, Al2O3 and TiO2 are widely used for Claus reactions; nevertheless, they are not active for conversion of CS2 at lower temperatures. In this context, our approach in this research is using nanofibrous La(III)-doped TiO2 as a new Claus catalyst. La(III) is incorporated into titanium-oxo-acetate complexes via a one-pot sol-gel process, followed by calcination to form a nanofibrous xerogel. Because the nanofibers join together to form a connected network, the xerogel monolith has large macroporosity and exhibits a low density. The exterior surface of the nanofibers, which makes a large contribution to the surface area, remains intact under harsh conditions and thereby is accessible by the reactants. In addition, the La(III) doped TiO2 exhibits more Lewis-base activity that is effective for CS2 conversion. For comparison, TiO2 xerogels were deposited with La(III) by means of an impregnation method and also tested for Claus reaction activity; however, the catalytic performance of this material was reduced compared to the pure TiO2 counterpart. On the basis of characterization studies on these catalysts, it is concluded that (i) a good distribution of La(III) in TiO2 matrix and (ii) the method of La(III) incorporation are important for CS2 conversion.