Co3O4 anchored on biochar derived from chitosan (Co3O4@BCC) as a catalyst to efficiently activate peroxymonosulfate (PMS) for degradation of phenacetin.

Chitosan, as a bio-friendly and abundant biochar precursor, was employed to prepare cobalt-based catalyst (Co3O4@BCC) by calcination for activating peroxymonosulfate (PMS) to degrade phenacetin (PNT). Various characterization technologies and experimental designs were performed to investigate the physicochemical properties and catalytic performance of Co3O4@BCC. Approximately 99.0% of phenacetin (10 mg/L) was degraded in the system of Co3O4@BCC (0.05 g/L)/PMS (1.0 mM) within 15 min and the rate constant was 6 times higher than that in the system of Co3O4 (0.05 g/L)/PMS (1.0 mM). The results demonstrated that BCC as a carrier not only dispersed Co3O4 nanoparticles and improved the stability of catalyst, but also provided abundant electron-rich groups to facilitate the activation of PMS and the production of reactive oxygen species (ROS). Co3O4@BCC composite also exhibited good universality and reusability. More than 90% of BPA, SIZ and CAP was degraded by Co3O4@BCC activated PMS within 15 min at pH 7. The degradation rate of PNT was recovered from 90% to 98.0% via the regeneration of the used catalyst after the third run (calcination at 400 °C for 5 min). SO4•-, •OH and 1O2 were identified to be responsible for PNT degradation. Furthermore, the activation mechanism of PMS and the possible pathways of PNT degradation were reasonably speculated according to the results of electron paramagnetic resonance (EPR), X-ray photoelectron spectroscopy (XPS), quenching experiments and HPLC-TOF-MS2. This study explored the application of chitosan as a recycled material and provides a feasible strategy for designing and fabricating environmentally friendly and efficient catalysts for PMS activation to degrade organic pollutants.

Thermodynamic Properties of 3- and 4-Ethoxyacetanilides between 80 and 480 K.

In this work, we present a comprehensive study of the thermodynamic properties of 3-and 4-ethoxyacetanilides. The heat capacities in crystalline, liquid, and supercooled liquid states from 80 to 475 K were obtained using adiabatic, differential scanning (DSC), and fast scanning (FSC) calorimetries. The fusion enthalpies at Tm were combined from DSC measurement results and the literature data. The fusion enthalpies at 298.15 K were evaluated in two independent ways: adjusted according to Kirchhoff's law of thermochemistry, and using Hess' law. For the latter approach, the enthalpies of the solution in DMF in crystalline and supercooled liquid states were derived. The values obtained by the two methods are consistent with each other. The standard thermodynamic functions (entropy, enthalpy, and Gibbs energy) between 80 and 470 K were calculated.

Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity.

OBJECTIVE: Although acetaminophen is one of the most widely used over-the-counter drugs, the mechanisms by which this classical drug exerts analgesic, hepatotoxic, and nephrotoxic effects remain unclear. We hypothesized that acetaminophen might act on cellular membranes of nerves, liver, and kidneys. In order to verify this hypothesis, we studied the interactivity of acetaminophen with biomimetic lipid bilayer membranes by comparing with structurally related phenacetin. METHODS: Liposomal membranes (unilamellar vesicles suspended in the buffer of pH 7.4) were prepared with phospholipids and cholesterol to mimic the membrane lipid composition of neuronal cells, hepatocytes, and nephrocytes. They were subjected to reactions with acetaminophen and phenacetin at clinically relevant concentrations, followed by measuring fluorescence polarization to determine their membrane interactivity to modify membrane fluidity. RESULTS: Acetaminophen and phenacetin interacted with neuro-mimetic and hepato-mimetic membranes to increase membrane fluidity at 10-100 µM. Both drugs were more effective in fluidizing hepato-mimetic membranes than neuro-mimetic membranes. Although the relative membrane-interacting potency was phenacetin >> acetaminophen in neuro-mimetic and hepato-mimetic membranes, such membrane effects conflicted with their relative analgesic and hepatotoxic effects. Acetaminophen and phenacetin strongly interacted with nephro-mimetic membranes to increase membrane fluidity at 2-100 µM and 0.1-100 µM, respectively. Phenacetin interacted significantly with nephro-mimetic membranes at lower concentrations (<2 µM) than acetaminophen, which was consistent with their relative nephrotoxic effects. CONCLUSION: In comparison with phenacetin, lipid composition-dependent membrane interactivity of acetaminophen could be related to nephrotoxicity but not to analgesic activity and hepatotoxicity.

Effects of paeoniflorin on the activities and mRNA expression of rat CYP1A2, CYP2C11 and CYP3A1 enzymes in vivo.

Paeoniflorin is the major constituent in extracts of the paeony root, the purpose of the present study was to assess the effects of paeoniflorin on the activities and mRNA expression of the rat hepatic drug-metabolizing enzymes cytochrome P450 (CYP1A2), CYP2C11 and CYP3A1 in vivo.Sprague-Dawley (SD) male rats were treated with paeoniflorin at the dosage of 25, 50 and 100 mg/kg or 0.9% sodium chloride solution by intragastric administration for 7 days, then were given probe drugs phenacetin (CYP1A2), tolbutamide (CYP2C11), or midazolam (CYP3A1) orally on the eighth day. Blood samples were collected at various times, and the plasma concentrations of the probe drugs were estimated with ultra-high-performance liquid chromatography. The mRNA expression levels of rat hepatic CYP1A2, CYP2C11 and CYP3A1 were analysed with real-time PCR.The pharmacokinetic results indicated that paeoniflorin inhibits the activities of CYP1A2, CYP2C11 and CYP3A1 in vivo. The effect was most pronounced on CYP3A1, according to the United States Food and Drug Administration classification of inhibitors of CYP3A, it reached the category of moderate inhibition. The mRNA expression levels of 3 CYP enzymes were also tended to be inhibited.We conclude that paeoniflorin can inhibit the activities of CYP1A2, CYP2C11 and CYP3A1 in vivo, which may affect the metabolism of drugs that are primarily dependent on these pathways.

Thermodynamic Characteristics of Phenacetin in Solid State and Saturated Solutions in Several Neat and Binary Solvents.

The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning calorimetry and spectroscopic solubility measurements. The temperature-related heat capacity values measured for both the solid and melt states were provided and used for precise determination of the values for ideal solubility, fusion thermodynamic functions, and activity coefficients in the studied solutions. Factors affecting the accuracy of these values were discussed in terms of various models of specific heat capacity difference for phenacetin in crystal and super-cooled liquid states. It was concluded that different properties have varying sensitivity in relation to the accuracy of heat capacity values. The values of temperature-related excess solubility in aqueous binary mixtures were interpreted using the Jouyban-Acree solubility equation for aqueous binary mixtures of methanol, DMSO, DMF, 1,4-dioxane, and acetonitrile. All binary solvent systems studied exhibited strong positive non-ideal deviations from an algebraic rule of mixing. Additionally, an interesting co-solvency phenomenon was observed with phenacetin solubility in aqueous mixtures with acetonitrile or 1,4-dioxane. The remaining three solvents acted as strong co-solvents.

Validation of an HPLC Method for the Simultaneous Quantification of Metabolic Reaction Products Catalysed by CYP2C11 Enzymes in Rat Liver Microsomes: In Vitro Inhibitory Effect of Salicylic Acid on CYP2C11 Enzyme.

The inhibitory effect of new chemical entities on rat liver P450 marker activities was investigated in a functional approach towards drug development. Treatment of colorectal cancer (CRC) and chemoprevention using salicylic acid has gained a lot of attention, mainly in the prevention of the onset of colon cancer. Thus, an in vitro inhibitory effect of salicylic acid on rat CYP2C11 activity was examined by using high performance liquid chromatography (HPLC). High performance liquid chromatography analysis of a CYP2C11 assay was developed on a reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) at 243 nm using 32% phosphate buffer (pH 3.36) and 68% methanol as a mobile phase. The CYP2C11 assay showed good linearity for all components (R2 > 0.999). Substrates and metabolites were found to be stable for up to 72 hours. Additionally, the method demonstrated good reproducibility, intra- and inter-day precision (<15%), acceptable recovery and accuracy (80%-120%), and low detection (1.3501 µM and 3.2757 µM) and quantitation limit values (4.914 µM and 9.927 µM) for 16α-hydroxytestosterone and testosterone, respectively. Salicylic acid acts reversibly as a noncompetitive (weak) inhibitor with Ki = 84.582 ± 2.67 µM (concentration of inhibitor to cause 50% inhibition of original enzyme activity (IC50) = 82.70 ± 2.67 µM) for CYP2C11 enzyme activity. This indicates a low potential to cause toxicity and drug-drug interactions.

[Eulogy to Prof. Dr. Med. Michael J. Mihatsch : Presentation of the Rudolf Virchow Medal 2019 of the German Society of Pathology]. / Laudatio auf Prof. Dr. med. Michael J. Mihatsch : Verleihung der Rudolf-Virchow-Medaille 2019 der Deutschen Gesellschaft für Pathologie.

Michael Mihatsch, born in 1943 in Gleiwitz, studied medicine in Bonn and Freiburg, and then went to Basel to begin studying pathology. In 1978, he became Assistant Professor at the University of Basel, and led the Institute there from 1988 until 2007. Mihatsch made Basel a center for prospective renal pathologists.His most significant achievement is the description of the connection between phenacetin administration and nephropathy with renal atrophy and the concomitant occurrence of urothelial carcinoma. His campaign against phenacetin finally contributed to a ban on the medication.His textbook Renal Pathology in Biopsy is a classic of medical literature.As a leading nephropathologist worldwide, Prof. Dr. Med. Michael J. Mihatsch received the Rudolf Virchow Medal of the German Society of Pathologists in 2019.

Increased Phenacetin Oxidation upon the L382V Substitution in Cytochrome P450 1A2 is Associated with Altered Substrate Binding Orientation.

Leucine382 of cytochrome P450 1A2 (CYP1A2) plays an important role in binding and O-dealkylation of phenacetin, with the L382V mutation increasing substrate oxidation (Huang and Szklarz, 2010, Drug Metab. Dispos. 38:1039⁻1045). This was attributed to altered substrate binding orientation, but no direct experimental evidence had been available. Therefore, in the current studies, we employed nuclear magnetic resonance (NMR) longitudinal (T1) relaxation measurements to investigate phenacetin binding orientations within the active site of CYP1A2 wild type (WT) and mutants. Paramagnetic relaxation time (T1P) for each proton of phenacetin was calculated from the T1 value obtained from the enzymes in ferric and ferrous-CO state in the presence of phenacetin, and used to model the orientation of phenacetin in the active site. All aromatic protons of phenacetin were nearly equidistant from the heme iron (6.34⁻8.03 Å). In contrast, the distance between the proton of the ⁻OCH2⁻ group, which is abstracted during phenacetin oxidation, and the heme iron, was much shorter in the L382V (5.93 Å) and L382V/N312L (5.96 Å) mutants compared to the N312L mutant (7.84 Å) and the wild type enzyme (6.55 Å), consistent with modeling results. These studies provide direct evidence for the molecular mechanism underlying increased oxidation of phenacetin upon the L382V mutation.

Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited.

As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.

Phenacetin promoted the rapid start-up and stable maintenance of partial nitrification: Responses of nitrifiers and antibiotic resistance genes.

Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.

Preparation of labeled human drug metabolites and drug-drug interaction-probes with fungal peroxygenases.

Enzymatic conversion of a drug can be an efficient alternative for the preparation of a complex metabolite compared with a multi-step chemical synthesis approach. Limitations exist for chemical methods for direct oxygen incorporation into organic molecules often suffering from low yields and unspecific oxidation and also for alternative whole-cell biotransformation processes, which require specific fermentation know-how. Stable oxygen-transferring biocatalysts such as unspecific peroxygenases (UPOs) could be an alternative for the synthesis of human drug metabolites and related stable isotope-labeled analogues. This work shows that UPOs can be used in combination with hydrogen/deuterium exchange for an efficient one-step process for the preparation of 4'-OH-diclofenac-d6. The scope of the reaction was investigated by screening of different peroxygenase subtypes for the transformation of selected deuterium-labeled substrates such as phenacetin-d3 or lidocaine-d3. Experiments with diclofenac-d7 revealed that the deuterium-labeling does not affect the kinetic parameters. By using the latter substrate and H2 (18) O2 as cosubstrate, it was possible to prepare a doubly isotope-labeled metabolite (4'-(18) OH-diclofenac-d6). UPOs offer certain practical advantages compared with P450 enzyme systems in terms of stability and ease of handling. Given these advantages, future work will expand the existing 'monooxygenation toolbox' of different fungal peroxygenases that mimic P450 in vitro reactions.

Isolation and Characterization of the Wastewater Micropollutant Phenacetin-Degrading Bacterium Rhodococcus sp. Strain PNT-23.

Phenacetin, an antipyretic and analgesic drug, poses a serious health risk to both humans and aquatic organisms, which is of concern since this micropollutant is frequently detected in various aquatic environments. However, rare pure bacterial cultures have been reported to degrade phenacetin. Therefore, in this study, the novel phenacetin-degrading strain PNT-23 was isolated from municipal wastewater and identified as a Rhodococcus sp. based on its morphology and 16S rRNA gene sequencing. The isolated strain could completely degrade 100 mg/L phenacetin at an inoculum concentration of OD600 1.5 within 80 h, utilizing the micropollutant as its sole carbon source for growth. Strain PNT-23 exhibited optimal growth in LB medium at 37 °C and a pH of 7.0 with 1% NaCl, while the optimal degradation conditions in minimal medium were 30 °C and a pH of 7.0 with 1% NaCl. Two key intermediates were identified during phenacetin biodegradation by the strain PNT-23: N-acetyl-4-aminophenol and 4-aminophenol. This study provides novel insights into the biodegradation of phenacetin using a pure bacterium culture, expands the known substrate spectra of Rhodococcus strains and presents a potential new candidate for the microbial removal of phenacetin in a diverse range of environments.

Acid-washed zero-valent aluminum as a highly efficient persulfate activator for degradation of phenacetin.

Phenacetin (PNT) is one of the most frequently detected nonsteroidal anti-inflammatory drugs in the water ecosystems, which poses a potential risk to environmental aquatic organisms. Acid-washed zero-valent aluminum (ZVAl) as a highly efficient activator for persulfate (PS) process was investigated to degrade PNT from the aqueous solution. The results indicated that acid-washed pretreatment for ZVAl could efficiently increase the degradation efficiency of PNT in the PS treatment. The degradation efficiency of PNT (50 µM) was up to 90% in 4 hours with the addition of 0.2 g/L acid-washed ZVAl and 8 mM PS at pH 6.8 and 25 °C. The PNT degradation followed pseudo-first order kinetics in the present system. High activator dosage, PS concentration, and reaction temperature could enhance the PNT degradation. The presence of inorganic anions (i.e., NO3-, HCO3-) and humic acid (HA) showed inhibitory effects on the PNT degradation. The reuse results illustrated the acid-washed ZVAl material would have continuous and efficient activation performance for PS to degrade the PNT. Radical scavenger experiments and electron paramagnetic resonance indicated that both SO4•- and •OH were major reactive species during the PNT degradation. The possible degradation pathways of PNT mainly included the break of C-N and C-O bonds and further oxidation.

N-(4-Eth-oxy-phen-yl)-3-oxobutanamide.

The title compound, C12H15NO3, crystallizes with Z' = 2 in space group Pca21 with the two independent mol-ecules having almost the same conformation, differing mostly at the end of the butanamide chain. A local inversion center near 1/8, 3/4, z relates the two mol-ecules, as is common for structures in this space group with Z' = 2. The mol-ecule crystallizes as the keto tautomer, and the ß-diketone moieties are twisted out of planarity, with O-C⋯C-O pseudo torsion angles of -74.4 (5) and -83.9 (5)°. The N-H group of each independent mol-ecule donates an inter-molecular hydrogen bond to an amide carbonyl oxygen atom by positive or negative translations along the b axis, thus forming anti-parallel chains propagating in the [010] direction.

Analysis of umbilical cord tissue as an indicator of in utero exposure to toxic adulterating substances.

In utero drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure, as drugs used by the mother during the third trimester may be retained in the UCT. Focus has also been given to potential adverse health effects among drug users, resulting from exposure to pharmacologically active adulterants and cutting agents in the street drug supply. The in utero effects of these substances have not been well studied in humans, nor has their presence been demonstrated as a means for assessing adverse health effects in the neonate. Here, we describe the application of a novel test method to analyze UCT for the presence of more than 20 common adulterating/cutting substances via LC/Q-TOF. In total, 300 de-identified UCT samples were analyzed-all had previously tested positive for cocaine or opiates. Generally, the positivity rates of individual compounds were similar between the Cocaine and Opiates Subgroups, apart from levamisole, xylazine, dipyrone (metabolites), and promethazine. Many of the adulterants used in the street drug supply do have legitimate medicinal/therapeutic uses, including several of the compounds most frequently detected in this study. Caffeine and lidocaine were the most frequently identified compounds both individually (>70% each) and in combination with each other. Alternatively, levamisole, an adulterant with no legitimate therapeutic use, was present in 12% of cases. Importantly, this data demonstrates that the detection of traditional drugs of abuse may serve as indicators of potential in utero exposure to toxic adulterating substances during gestation. While there is cause for concern with respect to any unintentional drug exposure, illicit drug use during pregnancy, including uncontrolled dosing, poly-adulterant consumption, and the interactions of these drug mixtures, produces a significant public health threat to the neonate which warrants further study.

N-(4-Meth-oxy-3-nitro-phen-yl)acetamide.

The title compound, C9H10N2O4, crystallizes with a disordered nitro group in twinned crystals. Both the meth-oxy group and the acetamide groups are nearly coplanar with the phenyl ring, and the C-N-C-O torsion angle [0.2 (4)°] is also insignificantly different from zero. Overall, the 12-atom meth-oxy-phenyl-acetamide group is nearly planar, with an r.m.s. deviation of 0.042 Å. The nitro group is twisted out of this plane by about 30°, disordered into two orientations with opposite senses of twist. In the crystal, the N-H group donates a hydrogen bond to a nitro oxygen atom, generating chains propagating in the [101] direction. The amide carbonyl oxygen atom is not involved in the hydrogen bonding.

An electrochemical sensor based on electrospun MoS2 @SnO2 modified carbon nanofiber composite materials for simultaneously detection of phenacetin and indomethacin.

SnO2 -CNF was prepared by coaxial blending technology, and MoS2 was grown uniformly on SnO2 -CNF composite by adding a hydrothermal post-treatment step. The uniform distribution of MoS2 on one-dimensional SnO2 -CNF can effectively establish a layered three-dimensional structure. Accordingly, the prepared MoS2 -coated SnO2 -CNF composite material has higher surface area and more active sites to obtain better electrochemical performance. We constructed an electrochemical sensor within the composite material with enhanced performance to realize the simultaneous and highly sensitive detection of phenacetin and indomethacin. The sensor has linear ranges of 0.050-7200 µM and 0.05-500 µM, respectively, and the detection limits were 0.016 µM and 0.013 µM. Furthermore, the sensor has good anti-interference ability and stability, which also achieves good recovery rate in the actual sample detection.

Inhibitory effects of Triphala on CYP isoforms in vitro and its pharmacokinetic interactions with phenacetin and midazolam in rats.

Context: Direct evidence of Triphala-drug interactions has not been provided to date. Objective: This study was aimed to determine the effects of Triphala on cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) in vitro, and to investigate pharmacokinetic interactions of Triphala with CYP-probes in rats. Materials and methods: Effects of Triphala on the activities of CYP isoforms and P-gp were examined using human liver microsomes (HLMs) and Caco-2 cells, respectively. Pharmacokinetic interactions between Triphala and CYP-probes (i.e., phenacetin and midazolam) were further examined in rats. Results: Triphala extract inhibited the activities of CYP isoforms in the order of CYP1A2>3A4>2C9>2D6 with the IC50 values of 23.6 ± 9.2, 28.1 ± 9.8, 30.41 ± 16.7 and 93.9 ± 27.5 µg/mL, respectively in HLMs. It exhibited a non-competitive inhibition of CYP1A2 and 2C9 with the K i values of 23.6 and 30.4 µg/mL, respectively, while its inhibition on CYP3A4 was competitive manner with the Ki values of 64.9 µg/mL. The inhibitory effects of Triphala on CYP1A2 and 3A4 were not time-dependent. Moreover, Triphala did not affect the P-gp activity in Caco-2 cells. Triphala, after its oral co-administration at 500 mg/kg, increased the bioavailabilities of phenacetin and midazolam by about 61.2% and 40.7%, respectively, in rats. Discussion and conclusions: Increases observed in the bioavailabilities of phenacetin and midazolam after oral co-administration of Triphala in rats provided a direct line of evidence to show Triphala-drug interactions via inhibition of CYP1A and CYP3A activities, respectively. These results, together with the lack of time-dependency of CYP 1A2 and 3A4 inhibition in vitro, suggested that the inhibitory effect of Triphala is primarily reversible.

Solubility Characteristics of Acetaminophen and Phenacetin in Binary Mixtures of Aqueous Organic Solvents: Experimental and Deep Machine Learning Screening of Green Dissolution Media.

The solubility of active pharmaceutical ingredients is a mandatory physicochemical characteristic in pharmaceutical practice. However, the number of potential solvents and their mixtures prevents direct measurements of all possible combinations for finding environmentally friendly, operational and cost-effective solubilizers. That is why support from theoretical screening seems to be valuable. Here, a collection of acetaminophen and phenacetin solubility data in neat and binary solvent mixtures was used for the development of a nonlinear deep machine learning model using new intuitive molecular descriptors derived from COSMO-RS computations. The literature dataset was augmented with results of new measurements in aqueous binary mixtures of 4-formylmorpholine, DMSO and DMF. The solubility values back-computed with the developed ensemble of neural networks are in perfect agreement with the experimental data, which enables the extensive screening of many combinations of solvents not studied experimentally within the applicability domain of the trained model. The final predictions were presented not only in the form of the set of optimal hyperparameters but also in a more intuitive way by the set of parameters of the Jouyban-Acree equation often used in the co-solvency domain. This new and effective approach is easily extendible to other systems, enabling the fast and reliable selection of candidates for new solvents and directing the experimental solubility screening of active pharmaceutical ingredients.

Metagenomics insights into the selective inhibition of NOB and comammox by phenacetin: Transcriptional activity, nitrogen metabolism and mechanistic understanding.

Phenacetin (PNCT), a common antipyretic and analgesic drug, is often used to treat fever and headache. However, the effect of PNCT on nitrifiers in wastewater treatment processes remains unclear. The practicability of attaining partial nitrification (PN) through inhibitor-PNCT was investigated in this study. The optimal treatment conditions of soaking once for 18 h with 2.50 × 10-3 g PNCT/(g MLSS) were applied to the PN stability experiment. The results showed that ammonia oxidation activity recovered quickly after 3 cycles of operation, while nitrite oxidation activity was suppressed steadily. In addition, average ammonium removal efficiency and nitrite accumulation ratio during 138 cycles could reach 94.94% and 85.38%, respectively. Complimentary DNA high-throughput sequencing and oligotyping analysis showed that the activity of Nitrosomonas would gradually surpass Nitrospira after PNCT treatment only once. The decrease of Nitrospira activity was accompanied by the simplification of oligotypes after PNCT treatment, while Nitrosomonas could adapt to PNCT stress by reducing the differences between oligotypes. Metagenomics revealed that the decrease in the number of NXR in the nitrogen metabolism pathways was the key reason for achieving PN. The potential mechanisms might be that the dominant nitrite-oxidizing bacteria and complete ammonia oxidizers were bio-killed by PNCT.