Investigation of the Structure of Atomically Dispersed NiNx Sites in Ni and N-Doped Carbon Electrocatalysts by 61Ni Mössbauer Spectroscopy and Simulations.

Ni and nitrogen-doped carbons are selective catalysts for CO2 reduction to CO (CO2R), but the hypothesized NiNx active sites are challenging to probe with traditional characterization methods. Here, we synthesize 61Ni-enriched model catalysts, termed 61NiPACN, in order to apply 61Ni Mössbauer spectroscopy using synchrotron radiation (61Ni-SR-MS) to characterize the structure of these atomically dispersed NiNx sites. First, we demonstrate that the CO2R results and standard characterization techniques (SEM, PXRD, XPS, XANES, EXAFS) point to the existence of dispersed Ni active sites. Then, 61Ni-SR-MS reveal significant internal magnetic fields of ∼5.4 T, which is characteristic of paramagnetic, high-spin Ni2+, in the 61NiPACN samples. Finally, theoretical calculations for a variety of Ni-Nx moieties confirm that high-spin Ni2+ is stable in non-planar, tetrahedrally distorted geometries, which results in calculated isotropic hyperfine coupling that is consistent with 61Ni-SR-MS measurements.

Impact of small diameter and low level of emission laser coronary atherectomy in patients with acute myocardial infarction.

Excimer laser coronary atherectomy (ELCA) is an effective treatment to remove intracoronary thrombi. In the present study, we compared in-hospital mortality in patients with acute myocardial infarction (AMI) who underwent conventional treatment and conventional treatment plus ELCA. Among 656 patients who were admitted to our hospital through the Tokyo CCU Network, 104 patients with AMI who were treated by percutaneous coronary intervention between January 2013 and December 2016 met inclusions criteria and underwent conventional treatment with ELCA (ELCA group) and 89 underwent conventional treatment alone (conventional group). We retrospectively evaluated in-hospital mortality within 30 days and used propensity score (PS) matching to reduce assignment bias and multivariate analysis to detect the predictors of in-hospital mortality. In-hospital mortality rate was significantly lower in the ELCA group before and after PS matching (2.9% vs. 13.5%, p = 0.006 before PS matching, and 2.8% vs. 14.1%, p = 0.016 after PS matching). After PS matching, ß-blocker or statins use, incidence of shock, Killip classification, and door-to-balloon time were not significantly different. A multivariate logistic regression analysis identified ELCA, dyslipidemia, shock, and left ventricular ejection fraction as independent predictors of in-hospital mortality (odds ratio (OR), 0.147, 95% confidence interval [CI], 0.022-0.959, p = 0.045; OR, 0.077, 95% CI, 0.007-0.805, p = 0.032; OR, 6.494, 95% CI, 1.228-34.34, p = 0.028; OR, 0.890, 95% CI, 0.828-0.957, p = 0.002, respectively). Our data indicate that ELCA with the small diameter and low level emission may reduce the in-hospital mortality compared to conventional methods in patients with AMI in drug-eluting stent era.

The Thermal Stability of the Collagen Triple Helix Is Tuned According to the Environmental Temperature.

Triple helix formation of procollagen occurs in the endoplasmic reticulum (ER) where the single-stranded α-chains of procollagen undergo extensive post-translational modifications. The modifications include prolyl 4- and 3-hydroxylations, lysyl hydroxylation, and following glycosylations. The modifications, especially prolyl 4-hydroxylation, enhance the thermal stability of the procollagen triple helix. Procollagen molecules are transported to the Golgi and secreted from the cell, after the triple helix is formed in the ER. In this study, we investigated the relationship between the thermal stability of the collagen triple helix and environmental temperature. We analyzed the number of collagen post-translational modifications and thermal melting temperature and α-chain composition of secreted type I collagen in zebrafish embryonic fibroblasts (ZF4) cultured at various temperatures (18, 23, 28, and 33 °C). The results revealed that thermal stability and other properties of collagen were almost constant when ZF4 cells were cultured below 28 °C. By contrast, at a higher temperature (33 °C), an increase in the number of post-translational modifications and a change in α-chain composition of type I collagen were observed; hence, the collagen acquired higher thermal stability. The results indicate that the thermal stability of collagen could be autonomously tuned according to the environmental temperature in poikilotherms.

Peptide precursors that acquire denatured collagen-hybridizing ability by O-to-N acyl migration at physiological pH.

Here, we report peptide probes with either single or cyclic double stranded collagen-like sequences that spontaneously acquire collagen-hybridizing ability at physiological pH. These peptides have ester bonds derived from O-acyl isopeptide units that are converted to amide bonds via intramolecular O-to-N acyl migration by a pH shift. The peptides that do not require pre-treatment for disassembly will be useful as prodrugs in theranostic treatments targeting unfolded collagen.

Long-Term Performance of Right Ventricular Implantable Cardioverter-Defibrillator Leads in Arrhythmogenic Right Ventricular Cardiomyopathy and Hypertrophic Cardiomyopathy.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (-3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (-0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

[Case of Recurrent Breast Cancer with BRCA2 Mutation Successfully Treated with Olaparib Therapy].

A 70-year-old woman was diagnosed with cT2N2M0 left triple negative breast cancer. She received neoadjuvant chemotherapy. Around 30 months after the surgery, she developed carcinomatous pericardial tamponade, carcinomatous pleurisy, and metastatic thyroid cancer due to the breast cancer. Around the same time, a BRCA2 mutation was confirmed. Thus, olaparib therapy was started. Around 45 days after the start of olaparib administration, the therapeutic effect was cPR. The treatment remains effective even after approximately 1 year.

A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2n P Library and SPOTs Method.

d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead-2n -peptide (OB2n P) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2n P library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-ß-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the µ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.

Cyclic Peptides for Efficient Detection of Collagen.

We report here a new class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), that efficiently hybridize with the triple-helix-forming portions of collagen. cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages. Enzyme-linked immunosorbent assays and western blotting analysis showed that cCMPs exhibit more potent affinity toward collagen than reported collagen-binding peptides and can specifically detect different collagen polypeptides in a mixture of proteins. Collagen secreted from cultured cells was detected by confocal microscopy with fluorescein-labeled cCMP. The cCMP is also shown to detect sensitively folding intermediates in the endoplasmic reticulum, something that was difficult to visualize with conventional collagen detectors. Molecular-dynamics simulations suggested that a cCMP forms a more stably hybridized product than its single-chain counterpart; this could explain why cCMP has higher affinity toward denatured collagen. These results indicate the usefulness of cCMPs as tools for detecting denatured collagen.

Early Transfer of Patients with Acute Heart Failure from a Core Hospital to Collaborating Hospitals and Their Prognoses.

Japan is facing problems associated with "heart failure (HF) pandemics" and bed shortages in core hospitals that can accommodate patients with acute HF. The prognosis is currently unknown for acute HF patients who were transferred from core hospitals to collaborating hospitals during the very early treatment phase and whose treatment strategies are in place.We enrolled 166 acute HF patients who were hospitalized between January 1, 2015, and December 31, 2015, and compared the conditions of transferred patients (n = 53, median duration before transfer = 6 days) and nontransferred patients (n = 113). The transferred and nontransferred patients had similar one-year mortality rates (24.5% versus 19.5%, log-rank P = 0.27) and composite one-year mortality and HF readmission rates (35.8% versus 31.0%, log-rank P = 0.32). Multivariate analysis determined that patient transfers were not associated with a higher composite endpoint (hazard ratio, 1.08; 95% confidence interval, 0.58-1.99, P = 0.82). Transferred patients with low composite congestion scores (CCSs) had significantly lower composite endpoints than those with high CCSs (23.5% versus 57.9%, log-rank P = 0.005).Acute HF patients who were transferred did not have inferior prognoses compared with nontransferred patients when the treatment strategies were correctly assumed by cardiologists. The implementation of early and strict decongestion strategies before transfer may be important for reducing cardiovascular events.

Structure-activity relationships and action mechanisms of collagen-like antimicrobial peptides.

An antimicrobial triple-helical peptide, R3, was previously obtained from a collagen-like combinatorial peptide library. In this research, based on structure-activity relationship studies of R3, a more potent peptide, RR4, with increased positive net charge and charge density relative to R3, was developed. RR4 exhibited antimicrobial activity against both Gram-negative and Gram-positive bacterial strains, including multidrug-resistant strains. Its action could be attributed to entry into cells and interactions with intercellular molecules such as DNA/RNA that inhibited cell division rather than increasing bacterial membrane permeability. Furthermore, RR4 exhibited remarkable stability in serum and low cytotoxicity.

Ferrimagnetic Cage Framework in Ca12Fe10Si4O32Cl6.

The positively charged cage framework of the natural mineral mayenite, which enables various species with negative charge to be stabilized, is one of the key structures to provide the new functionalities exploited in applications. Here we report the structural and magnetic properties of recently found eltyubyuite, Ca12Fe10Si4O32Cl6, which is the first compound bearing a transition metal oxide as a main constituent in the mayenite-type structure. From neutron powder diffraction measurements at T = 20 K and the low temperature Mössbauer measurement, we determined the magnetic structure of eltyubyuite to be a ferrimagnet with oppositely aligned magnetic moments of +3.17(3) and -3.05(8) µB in two tetrahedral Fe sites with different oxygen ligands, all bridging oxygens or mixed bridging and nonbridging oxygens. As far as is known, this result is likely to be a first example showing ferrimagnetism stemming from only tetrahedral Fe3+ ions. The reduced magnetic moment per Fe3+ and the resultant small net moment per unit cell of 22 µB at µ0H = 5 T and T = 15 K are attributed to strong covalency in much shorter Fe-O bonds in the FeO4 tetrahedra.

Collagen-like antimicrobial peptides.

Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016.

Synchrotron-based Nickel Mössbauer Spectroscopy.

We used a novel experimental setup to conduct the first synchrotron-based (61)Ni Mössbauer spectroscopy measurements in the energy domain on Ni coordination complexes and metalloproteins. A representative set of samples was chosen to demonstrate the potential of this approach. (61)NiCr2O4 was examined as a case with strong Zeeman splittings. Simulations of the spectra yielded an internal magnetic field of 44.6 T, consistent with previous work by the traditional (61)Ni Mössbauer approach with a radioactive source. A linear Ni amido complex, (61)Ni{N(SiMe3)Dipp}2, where Dipp = C6H3-2,6-(i)Pr2, was chosen as a sample with an "extreme" geometry and large quadrupole splitting. Finally, to demonstrate the feasibility of metalloprotein studies using synchrotron-based (61)Ni Mössbauer spectroscopy, we examined the spectra of (61)Ni-substituted rubredoxin in reduced and oxidized forms, along with [Et4N]2[(61)Ni(SPh)4] as a model compound. For each of the above samples, a reasonable spectrum could be obtained in ∼1 d. Given that there is still room for considerable improvement in experimental sensitivity, synchrotron-based (61)Ni Mössbauer spectroscopy appears to be a promising alternative to measurements with radioactive sources.

Cellular Uptake of IgG Using Collagen-Like Cell-Penetrating Peptides.

Cell-penetrating peptides (CPPs) are attractive tools for delivering macromolecules that have poor membrane permeability, such as antibodies, into cells. However, the major drawback of conventional CPPs is their instability in bodily fluids. We previously reported a novel CPP employing a collagen-like triple-helical structure that exhibited remarkable resistance against serum proteases. Herein, we report the delivery of full-length immunoglobulin G (IgG) antibody into cells using a triple-helical CPP. The CPP was conjugated to IgG via a one-pot reaction using 2-iminothiolane as a crosslinking reagent. The triple-helical CPP was less prone to being aggregated and neutralized by serum than was octaarginine, a conventional CPP. However, most of the conjugates were found to be entrapped in endosomes.

57Fe polarization-dependent synchrotron Mössbauer spectroscopy using a diamond phase plate and an iron borate nuclear Bragg monochromator.

Energy-domain (57)Fe polarization-dependent synchrotron radiation Mössbauer spectroscopy was developed by using a diamond X-ray phase plate and an iron borate nuclear Bragg monochromator. The former controls the polarization of the incident synchrotron radiation X-rays and the latter filters the (57)Fe-Mössbauer radiation with a narrow bandwidth of ∼3.4 Γ0 (Γ0 ≃ 4.7 neV: natural linewidth of the (57)Fe nucleus) from the broadband synchrotron radiation. The developed nuclear diffraction optics allowed (57)Fe-Mössbauer studies to be performed with various polarization states, i.e. linear polarization, circular polarization and non-polarization. In this paper, the spectrometer system, beam characterization, performance-test experiments and a grazing-incidence Mössbauer measurement of an isotope-enriched ((57)Fe: 95%) iron thin film are described.

Discrimination of thoracic vein potentials facilitated by atrial pacing during the isolation.

BACKGROUND: Although electrical thoracic vein (TV) isolation is an established strategy during atrial fibrillation (AF) ablation, discriminating TV potentials from far-field signals is critical for the achievement. METHODS AND RESULTS: One hundred consecutive drug-refractory symptomatic paroxysmal AF patients who underwent AF catheter ablation were included. All patients underwent circumferential pulmonary vein (PV) isolation during distal coronary sinus (CS) pacing with a cycle length of 600 ms. A superior vena cava (SVC) isolation was added during high right atrial (HRA) pacing with the same cycle length in 79 patients in whom SVC potentials were identified. The interval between the near-field PV potentials and far-field atrial signals significantly prolonged more during distal CS pacing than sinus rhythm (SR) in the left superior (26.0 [18.5-32.8] ms to 36.0 [24.3-55.5] ms, P < 0.01) and left inferior PVs (21.0 [14.0-30.0] ms to 40.0 [23.0-56.0] ms, P < 0.01), but not in the right superior (34.0 [20.0-40.0] ms to 23.0 [18.0-36.0] ms, P = 0.13) and right inferior PVs (22.0 [16.0-28.0] ms to 25.0 [18.0-38.0] ms, P = 0.05). The interval between the SVC potentials and far-field atrial signals significantly prolonged more during HRA pacing than SR (20.0 [0-32.0] ms to 34.0 [24.0-46.0] ms, P < 0.01). Electrical isolation was successfully achieved in all TVs without any complications except for transient right phrenic nerve palsy in two patients. CONCLUSIONS: Discrimination of ipsilateral left PVs and SVC potentials is facilitated by pacing from the distal CS and HRA, respectively. Better recognition of TV potentials would help to achieve electrical isolation.

A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging.

We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.

Variability of microcirculatory resistance index and its relationship with fractional flow reserve in patients with intermediate coronary artery lesions.

BACKGROUND: The relationship between the functional significance of epicardial coronary artery stenosis and microvascular resistance remains to be determined. Furthermore, little is known regarding the determinants of microvascular resistance in patients with intermediate coronary lesions. METHODS AND RESULTS: Using a pressure-temperature sensor-tipped guidewire, thermodilution-derived index of microcirculatory resistance (IMR) was measured, along with fractional flow reserve (FFR), in 131 coronary arteries of 104 patients with intermediate stenosis, in order to determine the relationship between IMR and clinical data. IMR varied widely (median, 20.8; range, 6.3-65.2), and no significant relationship was observed between IMR and FFR after IMR was corrected for coronary wedge pressure in the territories with functionally significant stenoses. There was no significant relationship between IMR and Framingham risk score, systematic coronary risk evaluation (SCORE), ACC/AHA lesion classification, or SYNTAX score. Right coronary artery (RCA) lesion location and history of hypertension were significantly associated with increased IMR. Multivariate analysis showed that RCA lesion location (odds ratio [OR], 4.52; 95% confidence interval [CI]: 1.84-11.11, P=0.001) and hypertension (OR, 3.03; 95% CI: 1.15-7.96, P=0.025) were independent predictors of increased IMR. CONCLUSIONS: Functional significance of intermediate coronary stenosis was not correlated with microvascular resistance of the perfusion territory. Intermediate coronary lesions may result in increased microcirculatory resistance irrespective of functional significance of the stenosis, with significant regional difference in microvascular resistance.

Usefulness of Balloon-Assisted Ultrasound-Guided Percutaneous Thrombin Injection to Femoral Artery Pseudoaneurysm by Transradial Artery Approach.

Balloon-Assisted Ultrasound-Guided Percutaneous Thrombin Injection (BATI) is useful for iatrogenic pseudoaneurysm. In previous reports, BATI for pseudoaneurysm of the femoral artery was performed by contralateral transfemoral approach. It has been reported that patients with obesity, hypertension, and diabetes have more hemorrhagic complications at the puncture site of the femoral artery. We report a case in which BATI by transradial artery approach was useful for patients with obesity, hypertension, and diabetes who were expected to be at high risk of hemorrhagic complications of transfemoral artery approach.

Observation of a critical charge mode in a strange metal.

Understanding the strange metallic behavior that develops at the brink of localization in quantum materials requires probing the underlying electronic charge dynamics. Using synchrotron radiation-based Mössbauer spectroscopy, we studied the charge fluctuations of the strange metal phase of ß-YbAlB4 as a function of temperature and pressure. We found that the usual single absorption peak in the Fermi-liquid regime splits into two peaks upon entering the critical regime. We interpret this spectrum as a single nuclear transition, modulated by nearby electronic valence fluctuations whose long time scales are further enhanced by the formation of charged polarons. These critical charge fluctuations may prove to be a distinct signature of strange metals.