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Iron-related disorders are among the most prevalent diseases worldwide. Systemic iron homeostasis requires hepcidin, a liver-derived hormone that controls iron mobilization through its molecular target ferroportin (FPN), the only known mammalian iron exporter. This pathway is perturbed in diseases that cause iron overload. Additionally, intestinal HIF-2α is essential for the local absorptive response to systemic iron deficiency and iron overload. Our data demonstrate a hetero-tissue crosstalk mechanism, whereby hepatic hepcidin regulated intestinal HIF-2α in iron deficiency, anemia, and iron overload. We show that FPN controlled cell-autonomous iron efflux to stabilize and activate HIF-2α by regulating the activity of iron-dependent intestinal prolyl hydroxylase domain enzymes. Pharmacological blockade of HIF-2α using a clinically relevant and highly specific inhibitor successfully treated iron overload in a mouse model. These findings demonstrate a molecular link between hepatic hepcidin and intestinal HIF-2α that controls physiological iron uptake and drives iron hyperabsorption during iron overload.

Recently, solution-electrode glow discharges (SEGDs) have shown great utility as ionization sources for mass spectrometry (MS). The solution composition of SEGD electrodes is pivotal to their performance as it influences analyte-ion formation. The performance of electrospray ionization is heavily dictated by spray-solution composition, which can alter ionization efficiency and pathways. While SEGDs produce Taylor cones similar to electrospray ionization, the influence of solution-electrode composition on molecular-ion formation has not been studied. Here, we examine how additives to an atmospheric-pressure solution-cathode glow discharge (SCGD) influence molecular ionization and fragmentation. The impact of several additives to the acidic solution of an SCGD ionization source was evaluated based on mass-spectrometric performance. Addition of methanol increased molecular- and fragment-ion signals for peptide angiotensin II. This effect is likely due to improved desolvation and a greater interaction of analyte molecules with glow-discharge species. Several high-boiling-point reagents were tested to examine changes in the ion signal, the average charge state, and the degree of fragmentation. Overall, these additives inhibited fragmentation but significantly lowered intact molecular-ion signals. Interestingly, loss of fragment ions trended with the boiling point of the reagent used. We hypothesize that analyte molecules become trapped in droplets produced at the solution-cathode surface. These droplets do not fully desolvate before escaping the discharge region, sparing analyte molecules from fragmentation. For low volatility additives, droplets do not desolvate, even as they enter the heated MS, which yields a loss in molecular ions. The changing composition of the SCGD solution alters analytical performance, but also provides insight into analyte ionization and fragmentation processes. [ABSTRACT FROM AUTHOR]

Time‐of‐flight mass spectrometry (TOFMS) is one of the simplest and most powerful approaches for mass spectrometry. Realization of the advantages inherent in TOFMS requires innovation in the theory and practice of the technique. Instrumental developments, in turn, create new capabilities that enable applications in chemical measurement. This review focuses on the recent advances in TOFMS instrumentation. New strategies for ion acceleration, multiplexed detection, miniaturized TOFMS instruments, approaches to extend the length of ion flight, and novel ion detection technologies are reviewed. Techniques that change the basic paradigm of TOFMS by measuring m/z based on ion flight distance are considered, as are applications at the frontiers of instrumental performance. © 2020 John Wiley & Sons Ltd. Mass Spec Rev [ABSTRACT FROM AUTHOR]

A new method of detection for ion chromatography (IC) is described that couples replacement-ion chromatography (RIC) with an atmospheric-pressure solution-cathode glow discharge (SCGD). In the new instrument, a conventional suppressed IC arrangement is followed by a “replacement column” that consists of a cation-exchange micromembrane suppressor continuously regenerated with Li2SO4. In this arrangement analytes are stoichiometrically converted to Li salts when they pass through the replacement column and are introduced into the SCGD, where they are detected indirectly by atomic emission spectrometry. Though found to be unsuitable for cation determinations, the SCGD–RIC instrument shows good repeatability (<3.5% peak area relative standard deviation), approximately 4 orders of linear dynamic range, universal calibration (similar molar sensitivity for anions of the same charge), and detection limits between 0.08 and 0.64 μg·mL-1 (25-μL injection) for several mono- and divalent anions. Deviations from the universal calibration were also observed and are critically evaluated. Optimal operating conditions are described, analytical figures of merit are presented, and background sources present in the system are characterized and explained. [ABSTRACT FROM AUTHOR]

Our research group earlier used dispersion that occurs during flow injection to detect and reduce matrix interference in inductively coupled plasma time of flight mass spectrometry (ICP-TOFMS). In the absence of a matrix interference, the ratio of signals from any two sample constituents should remain constant, independent of the dilution, over the course of a flow injection transient. However, when an interferent is present, the signal ratio from different analytes will change with dilution, owing to the difference in severity of the interference on specific analytes. As a result, matrix interference can be recognized (flagged) by monitoring the signal ratios of two analytes over the course of a flow injection transient; a ratio that changes over time indicates the presence of an interferent. The drawback of this earlier method was that dispersion, and therefore dilution, was somewhat element specific, causing the ratios to wander even when no interference existed. Here, a gradient HPLC pump is used to overcome this drawback by creating a longer, better-controlled dilution. Under these conditions, variation in dispersion between elements is negligible and difficulties associated with it are reduced or eliminated. Further, when an interference exists, the optimal dilution factor to reduce the interference to an acceptable level can be found from the gradient-dilution curve as the point where the signal ratio between two elements becomes constant. [ABSTRACT FROM AUTHOR]