Phoenix

A novel chiral coordination polymer, [Cu­(C₆H₅CH­(OH)­COO)­(μ-C₆H₅CH­(OH)­COO)] (<b>1</b>-L and <b>1</b>-D), was synthesized through a reaction of copper acetate with l-mandelic acid at room temperature. Although previously reported copper mandelate prepared by hydrothermal reaction was a centrosymmetric coordination polymer because of the racemization of mandelic acid, the current coordination polymer shows noncentrosymmetry and a completely different structure from that previously reported. The X-ray crystallography for <b>1</b>-L revealed that the copper center of the compound showed a highly distorted octahedral structure bridged by a chiral mandelate ligand in the unusual coordination mode to construct a one-dimensional (1D) zigzag chain structure. These 1D chains interdigitated each other to give a layered structure as a result of the formation of multiple aromatic interactions and hydrogen bonds between hydroxyl and carboxylate moieties at mandelate ligands. The coordination polymer <b>1</b>-L belongs to the noncentrosymmetric space group of C2 to show piezoelectric properties and second harmonic generation (SHG) activity

DataSheet_1_FZL, a dynamin-like protein localized to curved grana edges, is required for efficient photosynthetic electron transfer in Arabidopsis.zip

Photosynthetic electron transfer and its regulation processes take place on thylakoid membranes, and the thylakoid of vascular plants exhibits particularly intricate structure consisting of stacked grana and flat stroma lamellae. It is known that several membrane remodeling proteins contribute to maintain the thylakoid structure, and one putative example is FUZZY ONION LIKE (FZL). In this study, we re-evaluated the controversial function of FZL in thylakoid membrane remodeling and in photosynthesis. We investigated the sub-membrane localization of FZL and found that it is enriched on curved grana edges of thylakoid membranes, consistent with the previously proposed model that FZL mediates fusion of grana and stroma lamellae at the interfaces. The mature fzl thylakoid morphology characterized with the staggered and less connected grana seems to agree with this model as well. In the photosynthetic analysis, the fzl knockout mutants in Arabidopsis displayed reduced electron flow, likely resulting in higher oxidative levels of Photosystem I (PSI) and smaller proton motive force (pmf). However, nonphotochemical quenching (NPQ) of chlorophyll fluorescence was excessively enhanced considering the pmf levels in fzl, and we found that introducing kea3-1 mutation, lowering pH in thylakoid lumen, synergistically reinforced the photosynthetic disorder in the fzl mutant background. We also showed that state transitions normally occurred in fzl, and that they were not involved in the photosynthetic disorders in fzl. We discuss the possible mechanisms by which the altered thylakoid morphology in fzl leads to the photosynthetic modifications.</p

Theranostic Nanoparticles for MRI-Guided Thermochemotherapy: “Tight” Clustering of Magnetic Nanoparticles Boosts Relaxivity and Heat-Generation Power

Magnetic-resonance-imaging (MRI)-guided magnetic thermochemotherapy is a potentially invasive technique combining diagnosis and treatment. It requires the development of multifunctional nanoparticles with (1) biocompatibility, (2) high relaxivity, (3) high heat-generation power, (4) controlled drug release, and (5) tumor targeting. Here, we show the synthesis of such multifunctional nanoparticles (“Core–Shells”) and the feasibility of MRI-guided magnetic thermochemotherapy using the synthesized nanoparticles. “Tight” iron-oxide nanoparticle clustering to zero interparticle distance within the Core–Shells boosts the relaxivity and heat-generation power while maintaining biocompatibility. The initial Core–Shell drug release occurs in response to an alternating magnetic field (AMF) and continues gradually after removal of the AMF. Thus, a single Core–Shell dose realizes continuous chemotherapy over a period of days or weeks. The Core–Shells accumulate in abdomen tumors, facilitating MRI visualization. Subsequent AMF application induces heat generation and drug release within the tumors, inhibiting their growth. Core–Shell magnetic thermochemotherapy exhibits significantly higher therapeutic efficacy than both magnetic hyperthermia and chemotherapy alone. More importantly, there are minimal side effects. The findings of this study introduce new perspectives regarding the development of materials for MRI, magnetic hyperthermia, and drug delivery systems. Both conventional and novel iron-oxide-based materials may render theranostics (i.e., techniques fusing diagnosis and treatment) feasible

Organic–Inorganic Hybrid Nanoparticles for Tracking the Same Cells Seamlessly at the Cellular, Tissue, and Whole Body Levels

Techniques to elucidate the kinetics and distribution of the same cells in the whole body and in tissues are necessary for further studies of cancer, immunity, and regenerative medicine. Fluorescent imaging is a powerful technique for visualization of cells. However, current fluorescent probes are applicable in either the ultraviolet (UV)–visible (Vis) region (300–650 nm) or the biological transparency window (BTW, 650–900 nm), but not both. Thus, they cannot serve as fluorescent probes for both in vivo and in vitro imaging, and it is difficult to achieve imaging of the same cells seamlessly from the cellular level to the whole body and tissue levels using currently available fluorescent probes. Accordingly, in this paper, we describe organic–inorganic hybrid nanoparticles (HNPs) that could be used to achieve seamless tracking of the same cells. Within the HNPs, a porphyrin molecule, Vis-fluorophore, was surrounded by a siloxane chain, preventing the aggregation of porphyrin molecules. As a result, the porphyrin fluorescence was not quenched. Furthermore, indocyanine green (ICG), a BTW fluorophore, was localized on the HNP surface, leading to fluorescence resonance energy transfer (FRET) from porphyrin to ICG only near the HNP surface. Through the above structural design, the HNPs acquired both excitation (λ_ex) and emission (λ_em) wavelengths in the visible region and BTW, respectively, as well as large Stokes shifts. The HNP-labeled immune cells successfully and the labeled cells were separated easily from unlabeled cells by fluorescence-activated cell sorting. The kinetics of the labeled cells in the whole body were revealed by fluorescence imaging within BTW. Furthermore, the distributions of the same labeled cells were elucidated by histological analysis within the UV–vis region. Thus, the HNPs served as fluorescent probes for seamless tracking of the same cells

Red Blood Cell-Shaped Microparticles with a Red Blood Cell Membrane Demonstrate Prolonged Circulation Time in Blood

Prolonging the circulation time (CT) of microparticles (MPs) in the blood is key for a successful microparticle-based medicinal approach to serve as drug delivery systems (DDSs). Previously, we reported that MPs that mimic the shape of red blood cells (RBCs) avoid accumulation in the spleen and lungs. We now describe the effectiveness of mimicking not only the shape of RBCs but also their surface structure for the prolongation of CT. RBC-shaped MPs (RBC-MPs) were electrosprayed with cellulose and covered with a native RBC membrane (RBCM) collected from mouse blood. Seven hours after intravenous injection, approximately twice as many RBCM-covered RBC-MPs (RBC-MPs@RBCM) were present in the blood of mice compared to unmodified RBC-MPs. Twenty-four hours postinjection, the concentration of RBC-MPs@RBCM in the blood was 4 times higher. These findings suggest that an RBCM covering the MPs contributed to significant CT prolongation, which may positively impact their applications as DDSs

Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study

<div><p>Background</p><p>This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β₂-agonist (LABA).</p><p>Methods</p><p>285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209). Primary objective: to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV₁) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.</p><p>Results</p><p>At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV₁ and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.</p><p>Conclusions</p><p>The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://www.clinicaltrials.gov/ct2/show/NCT01340209?term=NCT01340209&rank=1" target="_blank">NCT01340209</a></p></div

Frequency of adverse events with incidence ≥4% in any treatment group (treated set).

<p>^aPatients were randomised 2:2:1 to the tiotropium Respimat 5 μg, tiotropium Respimat 2.5 μg and placebo Respimat groups, respectively.</p><p>^bThe preferred term ‘asthma’ summarises several lowest level terms.</p><p>Frequency of adverse events with incidence ≥4% in any treatment group (treated set).</p

CONSORT diagram.

<p>CONSORT diagram.</p

Additional file 10: of Overexpression of the protein disulfide isomerase AtCYO1 in chloroplasts slows dark-induced senescence in Arabidopsis

Table S1. Number of Cys residues in chloroplast proteins in Arabidopsis. (PDF 73 kb

Overall summary of adverse events (treated set).

<p>^aPatients were randomised 2:2:1 to the tiotropium Respimat 5 μg, tiotropium Respimat 2.5 μg and placebo Respimat groups, respectively.</p><p>^bAs determined by the investigator.</p><p>^cElevation of aspartate aminotransferase and/or alanine aminotransferase ≥3 × upper limit of normal combined with elevated total bilirubin ≥2 × upper limit of normal at the same visit.</p><p>^dAsthma worsening.</p><p>AE, adverse event.</p><p>Overall summary of adverse events (treated set).</p