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Nanoparticles (NPs) entering water systems are an emerging concern as NPs are more frequently manufactured and used. Single particle inductively coupled plasma-mass spectrometry (SP-ICP-MS) methods were validated to detect Zn- and Ce-containing NPs in surface and drinking water using a short dwell time of 0.1 ms or lower, ensuring precision in single particle detection while eliminating the need for sample preparation. Using this technique, information regarding NP size, size distribution, particle concentration, and dissolved ion concentrations was obtained simultaneously. The fates of Zn- and Ce-NPs, including those found in river water and added engineered NPs, were evaluated by simulating a typical drinking water treatment process. Lime softening, alum coagulation, powdered activated carbon sorption, and disinfection by free chlorine were simulated sequentially using river water. Lime softening removed 38–53 % of Zn-containing and ZnO NPs and >99 % of Ce-containing and CeO 2 NPs. Zn-containing and ZnO NP removal increased to 61–74 % and 77–79 % after alum coagulation and disinfection, respectively. Source and drinking water samples were collected from three large drinking water treatment facilities and analyzed for Zn- and Ce-containing NPs. Each facility had these types of NPs present. In all cases, particle concentrations were reduced by a minimum of 60 % and most were reduced by >95 % from source water to finished drinking water. This study concludes that uncoated ZnO and CeO 2 NPs may be effectively removed by conventional drinking water treatments including lime softening and alum coagulation.

Accurate determination of the drug-to-antibody ratio (DAR) of interchain cysteine-linked antibody–drug conjugates (ADCs) is challenging. High-resolution mass spectrometry (HRMS) analysis of the ADCs at the intact or subunit level provides a feasible way to measure the DAR. However, the measured DAR is usually lower than the true DAR because of the variation in ionization efficiency between different DAR species. In this work, we developed a novel standard-free HRMS method involving isotope-labeled payload conjugation, protease digestion, and liquid chromatography–HRMS (LC-HRMS) analysis for accurate determination of the DAR of the interchain cysteine-linked ADCs with cleavable or non-cleavable linkers. Isotope-labeled payload conjugations eliminated the structural and chemical differences between different DAR species and ensured that the drugs or payload-containing peptides could be separated from each other in the mass spectrometer. A papain digestion strategy for ADCs with cleavable linkers showed a DAR of 3.79, with a relative standard deviation (RSD) of 0.48 (n = 3). Similarly, the trypsin and chymotrypsin digestion strategy that is applicable to ADCs with non-cleavable linkers showed a DAR of 3.77 and an RSD of 0.86 (n = 3). The DAR determined by this method was consistent with the DAR of the ADCs that was measured by the UV/Vis method. This method will be very useful to researchers working in the field of ADC discovery and development.

This is the first comprehensive study to evaluate the cytotoxicity, biochemical mechanisms of toxicity, and oxidative DNA damage caused by exposing human bronchoalveolar carcinoma-derived cells (A549) to 70 and 420 nm ZnO particles. Particles of either size significantly reduced cell viability in a dose- and time-dependent manner within a rather narrow dosage range. Particle mass-based dosimetry and particle-specific surface area-based dosimetry yielded two distinct patterns of cytotoxicity in both 70 and 420 nm ZnO particles. Elevated levels of reactive oxygen species (ROS) resulted in intracellular oxidative stress, lipid peroxidation, cell membrane leakage, and oxidative DNA damage. The protective effect of N -acetylcysteine on ZnO-induced cytotoxicity further implicated oxidative stress in the cytotoxicity. Free Zn 2+ and metal impurities were not major contributors of ROS induction as indicated by limited free Zn 2+ cytotoxicity, extent of Zn 2+ dissociation in the cell culture medium, and inductively-coupled plasma-mass spectrometry metal analysis. We conclude that (1) exposure to both sizes of ZnO particles leads to dose- and time-dependent cytotoxicity reflected in oxidative stress, lipid peroxidation, cell membrane damage, and oxidative DNA damage, (2) ZnO particles exhibit a much steeper dose–response pattern unseen in other metal oxides, and (3) neither free Zn 2+ nor metal impurity in the ZnO particle samples is the cause of cytotoxicity.

The toxicology of nanomaterials is a blooming field of study, yet it is difficult to keep pace with the innovations in new materials and material applications. Those applications are quickly being introduced in research, industrial, and consumer settings. Even though the cytotoxicity of many types of nanoparticles has been demonstrated, the behavior of those particles in a biological environment is not yet fully known. This work characterized the following over time: protein adsorption on silica particle surfaces, the internalization of particles in human lung carcinoma (A549) cells when coated with different specific proteins or no proteins at all, and the cellular loss of particles following the removal of extracellular particles. Proteins were shown to quickly saturate the particle surface, followed by a competitive process of particle agglomeration and protein adsorption. Uptake of particles peaked at 8-10 h, and it was determined that, in this system, the charge of the protein-coated particles changed the rate of uptake if the charge difference was great enough. Cells internalized particles lacking any adsorbed proteins with approximately 3 times the rate of protein-coated particles with the same charge. Although particles exited cells over time, the process was slower than uptake and did not near completion within 24 h. Finally, analysis at the single cell level afforded observations of particle agglomerates loosely associated with cell membranes when serum was present in the culture medium, but in the absence of serum, particles adhered to the dish floor and formed smaller agglomerates on cell surfaces. Although data trends were easily distinguished, all samples showed considerable variation from cell to cell. [graphic removed]

Pteridines and their derivatives function as intermediates in the metabolism of several vitamins and cofactors, and their relevance to disease has inspired new efforts to study their roles as disease biomarkers. Recent analytical advances, such as the emergence of sensitive mass spectrometry techniques, new workflows for measuring pteridine derivatives in their native oxidation states and increased multiplexing capacities for the simultaneous determination of many pteridine derivatives, have enabled researchers to explore the roles of urinary pteridines as disease biomarkers at much lower levels with greater accuracy than with previous technologies or methods. As a result, urinary pteridines are being increasingly studied as putative cancer biomarkers with promising results being reported from exploratory studies. In addition, the role of urinary neopterin as a universal biomarker for immune system activation is being investigated in new diseases where it is anticipated to become a useful supplementary marker in clinical diagnostic settings. In summary, this review provides an overview of recent developments in the clinical study of urinary pteridines as disease biomarkers, covers the most promising aspects of advanced analytical techniques being developed for the determination of urinary pteridines and discusses the major challenges associated with implementing pteridine biomarkers in clinical laboratory settings.

Unconventional oil reservoirs have great potential to become significant sources of petroleum production in the future. Many shale oil systems consist of nanoscale pores and fractures that are significantly smaller than those from conventional reservoirs, and pore sizes are only slightly more than one order of magnitude of those of the saturating fluid molecules. This difference will cause abnormal wettability effect and typical fluid flow mechanisms in unconventional oil systems. Therefore, it is increasingly important to investigate fluid flow behaviours in nanoscale porous media. In this work, a lab-on-chip approach for the direct visualization of the water–oil flow in nanoscale channels was developed by using an advanced laser microscopy system combined with a nanofluidic chip. For the micro-scale study of interface transmission during the drainage and imbibition processes, parallel linear nanofluidic chips were used. A comprehensive study of water–oil flow behaviours is presented. During the drainage process, liquids tend to have a piston-like flow in nanoscale channels; both residual phase saturation and configuration affect the flow behaviour on such small scale; during the imbibition process, a fading-out phenomenon was observed. For a macroscale study of pressure and recovery relationships, unusual entrance pressure was discovered by using network nanofluidic chips comparing to conventional results.

Cancer biomarkers are biological, chemical or biophysical entities that are present in tumor tissues or body fluids which give valuable information about current and future behavior of cancer. This review discusses the applicability of biomarkers in different stages of cancer from cancer risk assessment to recurrence. In medical practice, biomarkers can be helpful in finding out one's potential cancer risk, confirming whether or not one is already affected with a particular type of cancer, to which drug will the cancer respond best and in what doses should it be administered, the effectiveness of the treatment and whether the cancer will recur. Although biomarker discovery and validation is a very challenging process, when considering its applications and advantages, it is well worth the effort.

Accurate determination of emerging contaminants in drinking water constitutes a major environmental challenge for which highly sensitive analytical methods are needed. This work details the development of a novel highly sensitive solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for simultaneous determination of a diverse panel of widely used trace contaminants, including two pharmaceuticals (fluoxetine and gemfibrozil), three pesticides (3-hydroxycarbofuran, azinphos-methyl, and chlorpyrifos), and two hormones (testosterone and progesterone) in water. The method is highly reproducible and sensitive with detection limits at subnanogram per liter level (0.05–0.5 ng/L). It was used to monitor the occurrence of these contaminants in source and drinking water across 18 drinking water treatment facilities in Missouri, USA in 1 year including cold winter and hot summer seasons. The experiment results indicated that all of the monitored contaminant concentrations are very low, lower than or close to the method detection limits, in the selected water treatment facilities. Pesticide concentrations were slightly elevated in some source waters during hot season, whereas slightly higher pharmaceuticals were observed during cold season. The concentrations of two hormones were lower than the limits of detection in all the water samples. These contaminants were present, if any, at below detection limits in all treated drinking water samples analyzed, suggesting that treatment processes effectively removed the contaminants studied herein.

A hydroxyapatite (HA, Ca₁₀(PO₄)₆(OH)₂), transformed from a calcium-containing borate glass, has been investigated for its protein adsorption and chromatographic characteristics. Microspheres of the borate glass were transformed into HA by reacting them with a 0.25 M phosphate (K₂HPO₄) solution for 24 h at 37 °C (pH 9.0). The HA microspheres with a diameter of 45–90 μm were hand packed into a steel column (4.6 mm × 80 mm) and used to separate a binary protein mixture of bovine serum albumin (BSA) and lysozyme. HA microspheres, with a diameter <45 μm, were used for separating a protein mixture of BSA, myoglobin, and lysozyme. These microspheres had a diameter that was 20–30 times larger than commercial HA column packing spherical particles, 2–3 μm, but these microspheres had a six times larger surface area and a more uniform spherical shape. These advantages compensated for their larger size and the separation results were comparable to those commercially available HA columns in the separation of the proteins studied. These unique HA microspheres, made from microspheres of a borate glass, are considered to be useful as packing materials for protein separation in chromatography.