Development and preliminary evaluation toward a new tuberculosis treatment monitoring tool: the PATHFAST TB LAM Ag assay.

The PATHFAST TB LAM Ag assay is based on a chemiluminescent enzyme immunoassay to quantify lipoarabinomannan (LAM) in sputum within 1 h, and was developed as an alternative to conventional culture methods for monitoring tuberculosis (TB) treatment. This study aimed to evaluate the analytical performance and initial clinical feasibility of using five variants, 178 non-tuberculous mycobacteria (NTM), 34 upper respiratory and oral cavity microorganisms, 100 sputum specimens from untreated patients, and potential interfering substances, including 27 drugs. The results reveled a single-site repeatability coefficient of variation (CV) of 5.

CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation.

Background: 27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma.

Star-Shaped Ruthenium Complexes as Prototypes of Molecular Gears.

The design and synthesis of two families of molecular-gear prototypes is reported, with the aim of assembling them into trains of gears on a surface and ultimately achieving controlled intermolecular gearing motion. These piano-stool ruthenium complexes incorporate a hydrotris(indazolyl)borate moiety as tripodal rotation axle and a pentaarylcyclopentadienyl ligand as star-shaped cogwheel, equipped with five teeth ranging from pseudo-1D aryl groups to large planar 2D paddles. A divergent synthetic approach was followed, starting from a pentakis(p-bromophenyl)cyclopentadienyl ruthenium(II) complex as key precursor or from its iodinated counterpart, obtained by copper-catalyzed aromatic Br/I exchange.

Hierarchical Emergence and Dynamic Control of Chirality in a Photoresponsive Dinuclear Complex.

Chiroptical photoswitches are of interest from a viewpoint of applications in advanced information technologies. We report dynamic on-off photoswitching of circularly polarized luminescence (CPL) in a binuclear europium complex system. Two coordination units are arranged closely in a chiral fashion by a photoresponsive ligand with a one-handed helical structure.

Production of reactive persulfide species in chronic obstructive pulmonary disease.

Background: Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine γ-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.

Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease.

Rationale: Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor β superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence.

Development of a Miniature Mass Spectrometer and an Automated Detector for Sampling Explosive Materials.

The development of a robust ionization source using the counter-flow APCI, miniature mass spectrometer, and an automated sampling system for detecting explosives are described. These development efforts using mass spectrometry were made in order to improve the efficiencies of on-site detection in areas such as security, environmental, and industrial applications. A development team, including the author, has struggled for nearly 20 years to enhance the robustness and reduce the size of mass spectrometers to meet the requirements needed for on-site applications.

Extracellular ATP is involved in dsRNA-induced MUC5AC production via P2Y2R in human airway epithelium.

Background: In response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations.

Fast and Efficient Oxidative Cycloreversion Reaction of a π-Extended Photochromic Terarylene.

We report herein a dramatic improvement in the kinetics and efficiency of an oxidative cycloreversion reaction of photochromic dithiazolylthiazoles. The cycloreversion reaction of a colored isomer of dithiazolylthiazole proceeds not only by photo-irradiation, but also through chemical oxidation with a net efficiency far exceeding 100 % owing to a chain reaction mechanism. By introducing aromatic groups on the reactive carbon atoms at the ends of a photoreactive 6π system in a dithiazolylthiazole, the net bleaching reaction rates were increased by up to 1300-fold, and turnover rates increased by two orders of magnitude.

27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells.

Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells.

Photoswitching of an intramolecular chiral stack in a helical tetrathiazole.

On-off photoswitching of circularly polarized luminescence was achieved using a pyrene-bearing helical tetrathiazole, in which two pyrene fluorophores stack in a chiral fashion (folded state). The pyrene-excimer based CPL was reversibly controlled by a geometrical change of the tetrathiazole upon photoisomerization.

Probe Heating Method for the Analysis of Solid Samples Using a Portable Mass Spectrometer.

We previously reported on the development of a portable mass spectrometer for the onsite screening of illicit drugs, but our previous sampling system could only be used for liquid samples. In this study, we report on an attempt to develop a probe heating method that also permits solid samples to be analyzed using a portable mass spectrometer. An aluminum rod is used as the sampling probe.

Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease.

Background: Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD). A large population of patients with COPD also have pulmonary hypertension. Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases.

Synthesis, structure, and properties of α,β-linked oligothiazoles with controlled sequence.

α,β-Linked oligothiazoles with head-to-tail connectivity are presented as a new family of helical scaffolds. Combinations of palladium-catalyzed cross-coupling reactions at the 5- and 4-positions of 2-phenylthiazole led to the synthesis of oligo(2-phenylthiazoles) with ortho linkages with a variety of defined sequences. The secondary structures of the α,β-linked oligo(2-phenylthiazoles) showed a clear dependence on their sequences.

Elucidating the sequence of intact bioactive peptides by using electron capture dissociation and hot electron capture dissociation in a linear radio-frequency quadrupole ion trap.

Rationale: Electron capture dissociation (ECD) is useful tool for sequencing of peptides and proteins with post-translational modifications. To increase the sequence coverage for peptides and proteins, it is important to develop ECD device with high fragmentation efficiency.

Methods: Sequence analysis of intact undigested bioactive peptides (3000-5000 Da) was performed by use of electron capture dissociation (rf-ECD) and collision-induced dissociation (CID) in a linear radio-frequency quadrupole ion trap that was coupled to a time-of-flight mass spectrometer.

Sensitive low-pressure dielectric barrier discharge ion source.

Rationale: We developed a novel highly sensitive soft ionization method: a low-pressure dielectric barrier discharge ionization (LP-DBDI) source. In this configuration, samples pass through the inside of a dielectric barrier discharge (DBD). Since samples pass through a DBD and its plasma jet, high ionization efficiency is expected.

High-throughput walkthrough detection portal for counter terrorism: detection of triacetone triperoxide (TATP) vapor by atmospheric-pressure chemical ionization ion trap mass spectrometry.

With the aim of improving security, a high-throughput portal system for detecting triacetone triperoxide (TATP) vapor emitted from passengers and luggage was developed. The portal system consists of a push-pull air sampler, an atmospheric-pressure chemical ionization (APCI) ion source, and an explosives detector based on mass spectrometry. To improve the sensitivity of the explosives detector, a novel linear ion trap mass spectrometer with wire electrodes (wire-LIT) is installed in the portal system.

Mass-selective axial ejection from a linear ion trap with a direct current extraction field.

We have developed a new mass-selective axial ejection method from a linear ion trap (LIT). In this method, a set consisting of a trap wire lens and an extraction wire lens positioned orthogonally to each other was placed between quadrupole rods. The trap wire lens confines the ions inside the trap, and the extraction wire axially extracts ions from the trap.

Fast multiple electron capture dissociation in a linear radio frequency quadrupole ion trap.

We developed a fast electron capture dissociation (ECD) device using a linear radio frequency-quadrupole (RFQ) ion trap. The device dissociated peptides and proteins using a focused electron beam with an intensity of 0.5 microA and a diameter of 1 mm.

Duty cycle enhancement of an orthogonal acceleration TOF mass spectrometer using an axially-resonant excitation linear ion trap.

We report a new technique to enhance detection duty cycle of an orthogonal-acceleration time-of-flight mass spectrometer (oaTOF) over a broad mass range. To this end, we used an axially-resonant-excitation linear ion trap, which ejects ions axially and mass selectively into a non-mass-selective linear ion trap in front of the TOF pusher. A delay between the ejection timing of the non-mass-selective LIT and the push timing of the oaTOF was swept mass-synchronously with the axially-resonant-excitation linear ion trap, so that ions are detected with duty cycle larger than 60% over a wide mass range from m/z 174.

'Information-Based-Acquisition' (IBA) technique with an ion-trap/time-of-flight mass spectrometer for high-throughput and reliable protein profiling.

Highly complex protein mixtures can be analyzed after proteolysis using liquid chromatography/mass spectrometry (LC/MS). In an LC/MS run, intense peptide ions originating from high-abundance proteins are preferentially analyzed using tandem mass spectrometry (MS(2)), so obtaining the MS(2) spectra of peptide ions from low-abundance proteins is difficult even if such ions are detected. Furthermore, the MS(2) spectra may produce insufficient information to identify the peptides or proteins.

Mass selective ejection by axial resonant excitation from a linear ion trap.

We describe a new mass selective ejection method from a linear ion trap, which we call axial resonant excitation (AREX). A set of vane lenses are inserted between each quadrupole rod to produce electrostatic potential that is approximately harmonic along the central axis of the quadrupole field. After ions with specific m/z are resonantly oscillated in the axial direction, the ions are mass selectively ejected in the axial direction.

Dual linear ion trap/orthogonal acceleration time-of-flight mass spectrometer with improved precursor ion selectivity.

A new hybrid mass spectrometer based on dual linear ion traps (LITs) and an orthogonal acceleration time-of-flight mass spectrometer (oaTOF), that can achieve MS(n) analysis and high-mass-accuracy detection with high sensitivity, has been developed. Dual-LIT was necessary because, in a single LIT plus oaTOF combination, the LIT pressure favorable for high precursor selectivity in MS(n) analysis (less than 1 mTorr) was far different from an optimum damping pressure (50-100 mTorr) for efficient connection to the TOF mass spectrometer. A dual-LIT solved this problem of inconsistency of the optimum pressures by using the first LIT for MS(n) analysis and the second LIT for collisional damping.