The present study focuses on the effects of nitrogen (N) ion implantation in vertically aligned ZnO nanorod arrays (NRAs) and the photocatalytic degradation of acetaminophen. The X-ray diffraction of these NRAs exhibit a wurtzite structure with a predominant (002) diffraction peak that shifts slightly after N-ion implantation. The field emission scanning electron microscopic images of as-prepared NRAs show a length of ∼4 μm and diameter of ∼150 nm. UV-visible spectroscopy reveals that the band gap of pristine ZnO NRAs decreases from 3.2 to 2.18 eV after N-ion implantation. Under visible irradiation, the N-ion-implanted ZnO catalyst exhibits significant enhancement of the photocatalytic degradation of acetaminophen from 60.0 to 98.46% for 120 min.

A boron-doped diamond (BDD) has been widely used as an outstanding electrode for constructing high-performance electrochemical biosensors. In this paper, we fabricated a novel electrode combined of nanometer-sized graphite-BDD film (NG-BDD) by chemical vapor deposition. The nanometer-sized graphite (NG) is formed on the (111) facet of BDD via converting an sp3 diamond structure to an sp2 graphitic phase at high temperature in boron-rich ambient. The electrode was characterized by means of scanning electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. This NG-BDD was performed as an electrode of electrochemical biosensor to detect trace acetaminophen (APAP) accurately. Cyclic voltammetry and differential normal pulse voltammetry are used to investigate the overall performance of the electrochemical device. The sensor has a linear electrochemical response to APAP in the concentration range of 0.02-50 μM, and the detection limit is estimated to be as low as 5 nM. The research has resulted in a solution of constructing a reusable NG-BDD sensor to detect APAP with stability and show potential in extensive application.

The purpose of this study is to explore the emulsion liquid membrane stability for acetaminophen (ACTP) removal from aqueous solution. In this work, the membrane phase was prepared by dissolving trioctylamine (TOA) with kerosene and Span80. The stability of the emulsion in terms of emulsion size, membrane breakage, and its efficiency in removing ACTP was considered for the optimization of parameters. Investigation on the stability of emulsion was carried out by manipulating the concentration of stripping agent, agitation speed, extraction time, and treat ratio. The best condition to produce a very stable emulsion was achieved at 0.1 M of stripping agent concentration, with 300 rpm of agitation speed for 3 min of extraction time with a treat ratio of 3:1. Eighty-five percent of ACTP successfully stripped into the emulsion with minimum membrane breakage of 0.17% through this experiment.

Coal fly ash was decorated with a graphene oxide-tungsten oxide nanorods nanocomposite (CFA/GO/WO3NRs nanocomposite) via a hydrothermal method and applied for the remediation of lead (Pb2+ ions). The Pb2+ ion-loaded spent adsorbent (CFA/GO/WO3NRs + Pb2+ nanocomposite) was reused for the photodegradation of acetaminophen. CFA/GO/WO3NRs + Pb2+ nanocomposite displayed rapid removal of Pb2+ ions. Pseudo-second-order kinetics and the Langmuir isotherm model described the adsorption data. The adsorption capacity of the CFA/GO/WO3NRs nanocomposite was 41.51 mg/g for the removal of Pb2+ ions. Additionally, the Pb2+ ion-loaded spent adsorbent significantly influenced the degradation of acetaminophen by photocatalysis where 93% degradation was observed. It is worthy to note the reuse application of Pb2+ ion-loaded spent adsorbent as a photocatalyst, which will significantly reduce the secondary waste obtained from conventional adsorption methods.

Idiosyncratic drug reactions are unpredictable adverse reactions. Although most such adverse reactions appear to be immune mediated, their exact mechanism(s) remain elusive. The idiosyncratic drug reaction most associated with serious consequences is idiosyncratic drug-induced liver injury (IDILI). We have developed a mouse model of amodiaquine (AQ)-induced liver injury that reflects the clinical characteristics of IDILI in humans. This was accomplished by impairing immune tolerance by using PD-1-/- mice and an antibody against CTLA-4. PD-1 and CTLA-4 are known negative regulators of lymphocyte activation, which promote immune tolerance. Immune checkpoint inhibitors have become important tools for the treatment of cancer. However, as in our model, immune checkpoint inhibitors increase the risk of IDILI with drugs that have an incidence of causing liver injury. Agents such as 1-methyl-d-tryptophan (D-1-MT), an inhibitor of the immunosuppressive indoleamine 2,3-dioxygenase (IDO) enzyme, have also been proposed as anti-cancer treatments. Another possible risk factor for the induction of an immune response is the release of danger-associated molecular patterns (DAMPs). Acetaminophen (APAP) is known to cause acute liver injury, and it is likely to cause the release of DAMPs. Therefore, either of these agents could increase the risk of IDILI, although through different mechanisms. If true, then this would have clinical implications. We found that co-treatment with D-1-MT paradoxically decreased liver injury in our model, and although APAP appeared to slightly increase AQ-induced liver injury, the difference was not significant. Such results highlight the complexity of the immune response, which makes potential interactions difficult to predict.

Sampling and extraction of chemical residues present on flat or curved surfaces as well as touch-sensitive objects are challenging. Hydrogels are characterized by high mechanical flexibility and water content. Thus, they are an ideal medium for transferring water-soluble analytes from a sampled surface to the next stage of an analytical workflow. Here, we demonstrate gel-phase microextraction (GPME), in which disks of blended hydrogels are utilized to lift traces of water-soluble substances adsorbed on surfaces. The protocol has been optimized in a series of tests involving fluorometric and mass spectrometric measurements. Compared with the pure agarose hydrogel, most of the tested blended hydrogels provide a higher efficiency for the sampling/extraction of a model analyte, fluorescein. The blended hydrogel disks are incorporated into three-dimensional (3D)-printed acrylonitrile-butadiene-styrene chips to create easy-to-use sampling probes. We exemplify the suitability of this improved GPME approach in sampling chemical residues present on the skin, glass, and daily use objects. In these tests, the extracts were analyzed on a triple quadrupole mass spectrometer fitted with an electrospray ion source operated in the positive- and negative-ion modes. The method enabled the detection of diclofenac on excised porcine skin fragments exposed to a topical nonsteroidal anti-inflammatory drug and sweat residues (lactic acid) left on surfaces touched by humans. The limits of detection for diclofenac and lactic acid in hydrogel extract were 6.4 × 10-6 and 2.1 × 10-5 M, respectively. In a model experiment, conducted using the presented approach, the amount of lactic acid on a glass slide with fingerprints was estimated to be ∼1.4 × 10-7 mol cm-2.

The concept of drug recycle by recovering active pharmaceutical ingredients (APIs) from unused tablets and capsules was demonstrated using acetaminophen, tetracycline HCl, and (R,S)-(±)-ibuprofen as case examples. The recovery process comprised three core unit operations: solid-liquid extraction, filtration, and crystallization. Recovery yields of 58.7 wt %, 73.1 wt %, and 67.6 wt % for acetaminophen, tetracycline HCl, and (R,S)-(±)-ibuprofen were achieved, respectively. More importantly, all of the APIs were of high purity based on high-performance liquid chromatography assay. The crystal forms of the recovered APIs were in conformity with the standards.

Multidevice capillary vibrating sharp-edge spray ionization (cVSSI) source parameters have been examined to determine their effects on conducting in-droplet hydrogen/deuterium exchange (HDX) experiments. Control experiments using select compounds indicate that the observed differences in mass spectral isotopic distributions obtained upon initiation of HDX result primarily from solution-phase reactions as opposed to gas-phase exchange. Preliminary studies have determined that robust HDX can only be achieved with the application of same-polarity voltage to both the analyte and the deuterium oxide reagent (D2O) cVSSI devices. Additionally, a similar HDX reactivity dependence on the voltage applied to the D2O device for various analytes is observed. Analyte and reagent flow experiments show that, for the multidevice cVSSI setup employed, there is a nonlinear dependence on the D2O reagent flow rate; increasing the D2O reagent flow by 100% results in only an ∼10-20% increase in deuterium incorporation for this setup. Instantaneous (subsecond) response times have been demonstrated in the initiation or termination of HDX, which is achieved by turning on or off the reagent cVSSI device piezoelectric transducer. The ability to distinguish isomeric species by in-droplet HDX is presented. Finally, a demonstration of a three-component cVSSI device setup to perform multiple (successive or in combination) in-droplet chemistries to enhance compound ionization and identification is presented and a hypothetical metabolomics workflow consisting of successive multidevice activation is briefly discussed.

The occurrence of contaminants of emerging concern (CECs) in water is an environmental issue that must be addressed to avoid damage to ecosystems and human health. Inspired by this current issue, in this work, we fabricated nanocellulose (NC) particles grafted with the block copolymer Jeffamine ED 600 (NC-Jeffamine) capable of adsorbing acetaminophen, sulfamethoxazole, and N,N-diethyl-meta-toluamide (DEET) from aqueous solution by electrostatic interactions. NC-Jeffamine composites were prepared by carboxylation of the NC surface via 2,2,6,6-tetramethyl-1-piperidinyloxy oxidation followed by the covalent attachment of Jeffamine using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysulfosuccinimide sodium salt reaction. The reaction was followed and confirmed by Fourier transform infrared and conductometric titration. The physical characterization was performed by thermogravimetric analysis, Brunauer-Emmett-Teller analysis, scanning electron microscopy, dynamic light scattering, and Z-potential analysis. This material was used to study the adsorption profile of three CECs in deionized water, namely, acetaminophen, sulfamethoxazole, and DEET. The adsorption isotherms were obtained at pH 3, 7, and 9, where the best adsorption results corresponded to pH 9 because of the uniform dispersion of the adsorbate in solution. A computational study based on the density functional theory determined that the possible interactions of the CECs with the adsorbent material were related to hydrogen bonds and/or van der Waals forces. The calculated binding energies were used as a descriptor to characterize the optimum adsorption site of CECs onto NC-Jeffamine.

We previously showed that commercially available rice peptide Oryza Peptide-P60 (OP60) increased the intracellular glutathione levels. This study aimed to evaluate the antioxidant potential of this peptide and assess its mechanism of action. Pretreatment of HepG2 cells with OP60 reduced the cytotoxicity caused by H2O2 or acetaminophen (APAP) (47.7 ± 1.3% or 12.2 ± 1.3% of the cytotoxicity for 5 mg/mL OP60 pretreatment compared to that in H2O2- or APAP-treated groups, respectively; p < 0.01) through the restoration of glutathione homeostasis. Moreover, OP60 elevated the mRNA level of genes encoding heavy and light subunits of γ-glutamylcysteine synthetase (γ-GCS) by 2.9 ± 0.1-fold and 2.7 ± 0.2-fold (p < 0.001), respectively, at 8 h and also increased the level of mRNA encoding other antioxidant enzymes. Besides, OP60 promoted Nrf2 nuclear translocation by 2.2 ± 0.3-fold (p < 0.05) after 8 h. Conversely, knockdown of Nrf2 inhibited the increase of the intracellular glutathione levels and suppressed the induction of antioxidant enzyme expression by OP60. In animal studies, OP60 prevented APAP-induced liver injury by suppressing glutathione depletion (from 0.19 ± 0.02 mmol/mg protein to 0.90 ± 0.02 mmol/mg protein; p < 0.01, by pretreatment with 500 mg/kg OP60) and increasing heavy subunit of γ-GCS and heme oxygenase-1 expression in the liver. Our results indicated that OP60 exhibits a cytoprotective effect via the Nrf2 signaling pathway and is one of the few peptides with excellent antioxidant properties.

The clinical use of some drugs, such as carbamazepine, phenytoin, and allopurinol, is often associated with adverse cutaneous reactions. The bioactivation of drugs into immunologically reactive metabolites by the liver is postulated to be the first step in initiating a downstream cascade of pathological immune responses. Current mechanistic understanding and the ability to predict such adverse drug cutaneous responses have been partly limited by the lack of appropriate cutaneous drug bioactivation experimental models. Although in vitro human liver models have been extensively investigated for predicting hepatotoxicity and drug-drug interactions, their ability to model the generation of antigenic reactive drug metabolites that are capable of eliciting immunological reactions is not well understood. Here, we employed a human progenitor cell (HepaRG)-derived hepatocyte model and established highly sensitive liquid chromatography-mass spectrometry analytical assays to generate and quantify different reactive metabolite species of three paradigm skin sensitizers, namely, carbamazepine, phenytoin, and allopurinol. We found that the generation of reactive drug metabolites by the HepaRG-hepatocytes was sensitive to the medium composition. In addition, a functional assay based on the activation of U937 myeloid cells into the antigen-presenting cell (APC) phenotype was established to evaluate the immunogenicity potential of the reactive drug metabolites produced by HepaRG-derived hepatocytes. We showed that the reactive drug metabolites of known skin sensitizers could significantly upregulate IL8, IL1β, and CD86 expressions in U937 cells compared to the metabolites from a nonskin sensitizer (i.e., acetaminophen). Thus, the extent of APC activation by HepaRG-hepatocytes conditioned medium containing reactive drug metabolites can potentially be used to predict their skin sensitization potential.