Temperature-Induced Sign Inversion of Circularly Polarized Luminescence of Binaphthyl-Bridged Tetrathiapyrenophanes.

D2-symmetric (R)-binaphthyl-bridged pyrenophanes containing thioether bonds were synthesized. The pyrenophanes exhibited the temperature-induced sign inversion of circularly polarized luminescence (CPL) while maintaining the emission wavelength and reversibility. The Δglum value reached 0.02, and the FL quenching by heat was negligible. The sign inversion of CPL originates from the inversion of intramolecular excimer chirality associated with excitation dynamics. The two pyrenes form a kinetically trapped left-handed twist excimer at low temperatures, while they form a thermodynamically favored right-handed twist excimer at high temperatures. The thioether linkers can impart flexibility suitable for the inversion of chirality of the excimers.

Coronary computed tomography angiographic detection of in-stent restenosis via deep learning reconstruction: a feasibility study.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

Core Transcriptome of Hydrogen Producing Marine Vibrios Reveals Contribution of Glycolysis in Their Efficient Hydrogen Production.

Pyruvate (Pyr) is the end product of the glycolysis pathway. Pyr is also renewable and is further metabolized to produce formate, which is the precursor of H2, via pyruvate formate lyase (PFL) under anaerobic conditions. The formate is excluded and re-imported via the formate channel and is then converted to H2 via the formate hydrogenlyase (FHL) complex. In H2 producing marine vibrios, such as Vibrio tritonius and Vibrio porteresiae in the Porteresiae clade of the family Vibrionaceae, apparent but inefficient H2 production from Pyr has been observed. To elucidate the molecular mechanism of why this inefficient H2 production is observed in Pry-metabolized marine vibrio cells and how glycolysis affects those H2 productions of marine vibrios, the "Core Transcriptome" approach to find common gene expressions of those two major H2 producing Vibrio species in Pyr metabolism was first applied. In the Pyr-metabolized vibrio cells, genes for the "Phosphoenolpyruvate (PEP)-Pyruvate-Oxalate (PPO)" node, due to energy saving, and PhoB-, RhaR-, and DeoR-regulons were regulated. Interestingly, a gene responsible for oxalate/formate family antiporter was up-regulated in Pyr-metabolized cells compared to those of Glc-metabolized cells, which provides new insights into the uses of alternative formate exclusion mechanics due to energy deficiencies in Pyr-metabolized marine vibrios cells. We further discuss the contribution of the Embden-Meyerhof-Parnas (EMP) pathway to efficient H2 production in marine vibrios.

Helix-forming aliphatic homo-δ-peptide foldamers based on the conformational restriction effects of cyclopropane.

Considerable effort has been directed toward developing artificial peptide-based foldamers. However, detailed structural analysis of δ-peptide foldamers consisting of only aliphatic δ-amino acids has not been reported. Herein, we rationally designed and stereoselectively synthesized aliphatic homo-δ-peptides forming a stable helical structure by using a chiral cyclopropane δ-amino acid as a monomer unit. Structural analysis of the homo-δ-peptides using circular dichroism, infrared, and NMR spectroscopy indicated that they form a stable 14-helical structure in solution. Furthermore, we successfully conducted X-ray crystallographic analysis of the homo-δ-peptides, demonstrating a right-handed 14-helical structure. This helical structure of the crystal was consistent with those predicted by theoretical calculations and those obtained based on NMR spectroscopy in solution. This stable helical structure is due to the effective restriction of the backbone conformation by the structural characteristics of cyclopropane. This work reports the first example of aliphatic homo-δ-peptide foldamers having a stable helical structure both in the solution and crystal states.

Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

Expression of Acetabular Labral Vascular Endothelial Growth Factor and Nerve Growth Factor Is Directly Associated with Hip Osteoarthritis Pain: Investigation by Immunohistochemical Staining.

The acetabular labrum enhances hip joint stability and plays a key role in osteoarthritis (OA) progression. Labral nerve endings contribute to hip OA pain. Moreover, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are associated with pain. Consequently, we analysed VEGF and NGF expression levels in the labrum and their roles in OA. Labra obtained from OA patients were stained immunohistochemically, and labral cells were cultured and subjected to a reverse transcription (RT)-polymerase chain reaction (PCR) to analyse VEGF and NGF mRNA expression. VEGF and NGF expression were compared in each region of the labrum. Correlations between VEGF and NGF expression and age, body mass index, Kellgren-Lawrence grade, Harris Hip Score, the visual analogue scale (VAS), and Krenn score were analysed, and the RT-PCR confirmed the findings. VEGF and NGF expression were high on the labral articular side, negatively correlated with the Krenn score, and positively correlated with the VAS in early OA. VEGF and NGF mRNA expression increased significantly in patients with severe pain and decreased significantly in severely degenerated labra. In early OA, VEGF and NGF expression in the acetabular labrum was associated with the occurrence of hip pain; therefore, these factors could be effective targets for pain management.

Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology　- A Serial Computed Tomography Angiography Study.

BACKGROUND: Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results: This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. CONCLUSIONS: In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Silencing of LRRFIP1 enhances the sensitivity of gemcitabine in pancreatic cancer cells by activating JNK/c-Jun signaling.

BACKGROUND: The epithelial-mesenchymal transition (EMT) in cancer cells has been shown to closely associate with the survival and drug resistance of cancer cells. We recently provided evidence that Wnt signal activator leucine-rich repeat in flightless-1-interacting protein 1 (LRRFIP1) regulates EMT in pancreatic cancer. LRRFIP1 silencing inhibits the translocation of ß-catenin to the nucleus, which led to reverse EMT in cancer cells. It was suggested that LRRFIP1 was implicated in gemcitabine sensitivity by regulating EMT signaling. METHODS: Gemcitabine chemosensitivity was investigated in LRRFIP1-knockdown pancreatic cancer cells (PANC-1 and MIA Paca-2). In addition, the effects of LRRFIP1 knockdown on JNK/SAPK (stress activated-protein kinase) signaling and apoptosis were evaluated. RESULTS: LRRFIP1 silencing accelerates gemcitabine-induced caspase activity and cell death in pancreatic cancer cells. It was also revealed that gemcitabine-induced phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun were increased in LRRFIP1 knockdown cells. The activation of JNK/c-Jun in LRRFIP1-knockdown cells was significantly diminished by the inhibition of Rac activity. It was confirmed that the acquisition of gemcitabine sensitivity by LRRFIP1 silencing largely depends on the stimulation of JNK/SAPK (stress activated-protein kinase) signaling. CONCLUSIONS: Our findings suggest that reversing EMT and transient activation of JNK might be essential for the gemcitabine sensitivity in LRRFIP1 knockdown pancreatic cancer cells. Our discoveries highlight the potential role of LRRFIP1 in the chemosensitivity related to the regulation of EMT signaling.

One-pot synthesis of tetrasubstituted 2-aminofurans via Au(I)-catalyzed cascade reaction of ynamides with propargylic alcohols.

One-pot synthesis of fully substituted 2-aminofurans via a Au(I)-catalyzed cascade reaction of ynamides and propargylic alcohol was realized. Hydroalkoxylation of ynamide with propargylic alcohol, Saucy-Marbet rearrangement, and cyclization of the resultant 3,4-dienamide sequentially proceeds in a one-pot reaction under highly mild conditions to give fully substituted 2-aminofurans.

Association of computed tomography-derived myocardial mass with fractional flow reserve-verified ischemia or subsequent therapeutic strategy.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)-verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P < 0.001). Addition of MVT to a model including patient characteristics (age, gender), visual assessment (≥ 70% stenosis, high-risk appearance), and quantitative CT vessel parameters [minimal lumen area (MLA), plaque burden at MLA, percent aggregate plaque volume] improved C-index (from 0.745 to 0.778, P = 0.020). Furthermore, of 130 vessels with FFR ≤ 0.80, myocardial volume exposed to ischemia (MVI) was larger in the vessels with early revascularization after FFR examination than those without (37.2 ± 20.0 vs. 26.8 ± 15.0 cm3, P = 0.003), and was independently associated with early revascularization [OR = 1.03, 95% confidence interval (1.02-1.11), P < 0.001]. Using an on-site CT workstation, MVT identified coronary arteries with FFR-verified ischemia easily and non-invasively, and MVI was associated with subsequent therapeutic strategy after FFR examinations.

Aerial floating 3D display device with lenticular-type naked-eye 3D display and a crossed-mirror array.

The depth feeling of a naked-eye 3D display is determined by the combination of the display and the lenticular lens, and because the parallax of the displayed image cannot be made stronger, providing a more stereoscopic effect is difficult. In this study, we propose a system that provides a clearer stereoscopic effect by enabling the naked-eye 3D display to be observed as an aerial stereoscopic image without the framework of the display. By comparing it with the conventional aerial display method, we demonstrate that it is possible to maintain the same level of resolution as the method without a crossed-mirror array and that natural stereoscopic view is possible.

Differences in the geometrical spinal shape in the sagittal plane according to age and magnitude of pelvic incidence in healthy elderly individuals.

BACKGROUND: Several studies indicated the influence of age and sex on spinal alignment using spino-pelvic radiographic parameters. However, information regarding the geometrical assessment of the sagittal spinal plane in the elderly population remains limited. This study aimed to determine the apices of lumbar lordosis and thoracic kyphosis, and spinal inflection point in elderly individuals and clarify the effect of age, sex, and pelvic incidence (PI) on sagittal geometry. METHODS: In total, 440 volunteers (193 men; 247 women) were enrolled. The spino-pelvic radiographic parameters were measured. The apices of thoracic kyphosis and lumbar lordosis, and the inflection point where the vertebral curvature changes from kyphosis to lordosis were investigated. We analyzed the differences in the sagittal curve shape according to the sex, age, and PI magnitude. RESULTS: On average, the apices of thoracic kyphosis and lumbar lordosis, and the inflection point were located at the levels of the T8/9 intervertebral disc, L3/4 disc, and L1 vertebra, respectively. Significant differences between men and women were observed with respect to the spino-pelvic parameters; however, the positions of the apices were significantly different only with respect to the lumbar apex offsets among individuals in their 70s. The inflectional point and apex of thoracic kyphosis among individuals aged >80 years were located significantly anteriorly and caudally in comparison to those among individuals aged <69 years. The apex of lumbar lordosis and the inflection point in individuals with high PI were located significantly anteriorly and cranially in comparison to those in individuals with low PI. CONCLUSIONS: The apices of thoracic kyphosis and lumbar lordosis, and the inflection point were located at the T8/9 intervertebral disc, L3/4 disc, and L1 vertebra, respectively. The shape of the sagittal spinal curve varied according to age and the magnitude of PI, and these findings cannot be evaluated using the conventional spino-pelvic parameters. Knowledge of standard geometrical spine shape could be useful for spinal deformity treatment in elderly patients.

Palladium-Catalyzed Decarboxylative Alkynylation of α-Acyloxyketones by C(sp3 )-O Bond Cleavage.

Palladium-catalyzed decarboxylative alkynylation of α-acyloxyketones triggered by C(sp3 )-O bond cleavage is disclosed. The decarboxylation strategy featuring a neutral reaction condition enabled an unprecedent catalytic alkynylation of a ketone enolate. The reaction was applied to a variety of substrates, giving desired products in good yields. We successfully obtained X-ray crystallography of a new palladium-enolate intermediate that was synthesized by a reaction of [Pd(cod)(CH2 TMS)2 ] with XPhos and α-acyloxyketone at room temperature, indicating facile C(sp3 )-O bond disconnection.

Prediction of sudden cardiac death in patients with chronic heart failure by regional washout rate in cardiac MIBG SPECT imaging.

BACKGROUND: The sympathetic nervous system provides an important trigger for major arrhythmic events through regional heterogeneity of sympathetic activity, which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR). There is little information available on the prognostic value of regional WR in SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with chronic heart failure (CHF). METHODS: We studied 73 CHF outpatients with LVEF < 40%. At study entry, the regional WR was measured in 17 segments on the polar map. We defined abnormal regional WR as both the regional WR range (maximum - minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15 normal controls. RESULTS: During a mean follow-up of 7.5 ± 4.1 years, 15 of 73 patients had SCD. The abnormal regional WR and abnormal global WR on planar images were significantly and independently associated with SCD. Patients with both the abnormal regional WR and global WR had a significantly higher risk of SCD than those with none of these criteria. CONCLUSIONS: The analysis of regional MIBG WR on SPECT imaging provides additional prognostic value to global WR on planar images for SCD prediction in CHF patients.

A scalable algorithm of numerical real-time path integral for quantum dissipative systems.

Numerical real-time path integration has been a practical method to study a quantum system under the influence of its environment. Performing the path integral computations, however, is a resource-demanding task in general, and implementing it is less straightforward with modern hardware architectures of massively parallel platforms. In this article, a numerical algorithm based on the quasiadiabatic propagator path integral scheme is proposed and shown to scale for systems with large size. As a case study of performance, the quantum dynamics of excitation energy transfer in the Fenna-Matthews-Olson complex is discussed, employing a vibronic model in which the system size can be varied simply by adding vibrational excitations.

Retraction Note to: Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate.

The Editor-in-Chief has retracted this article [1] because an investigation by Keio University has concluded that there are inaccuracies in the data reported.

Rhodium(I)-Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh-C Bond by a Tethered Hydroxy Group.

Rhodium(I)-catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh-C(sp2 ) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ-bond metathesis of a tethered O-H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.

Regulatory signatures of liver regeneration distilled by integrative analysis of mRNA, histone methylation, and proteomics.

The capacity of the liver to regenerate is likely to be encoded as a plasticity of molecular networks within the liver. By applying a combination of comprehensive analyses of the epigenome, transcriptome, and proteome, we herein depict the molecular landscape of liver regeneration. We demonstrated that histone H3 Lys-4 was trimethylated at the promoter regions of many loci, among which only a fraction, including cell-cycle-related genes, were transcriptionally up-regulated. A cistrome analysis guided by the histone methylation patterns and the transcriptome identified FOXM1 as the key transcription factor promoting liver regeneration, which was confirmed in vitro using a hepatocarcinoma cell line. The promoter regions of cell-cycle-related genes and Foxm1 acquired higher levels of trimethylated histone H3 Lys-4, suggesting that epigenetic regulations of these key regulatory genes define quiescence and regeneration of the liver cells. A quantitative proteome analysis of the regenerating liver revealed that conditional protein degradation also mediated regeneration-specific protein expression. These sets of informational resources should be useful for further investigations of liver regeneration.

Serial Change in Serum Chloride During Hospitalization Could Predict Heart Failure Death in Acute Decompensated Heart Failure Patients.

BACKGROUND: Although hyponatremia predicts morbidity and mortality in acute decompensated heart failure (ADHF), hypochloremia is also independently associated with poor prognosis in ADHF. Little is known, however, about the prognostic value of serial change in serum chloride during hospitalization in ADHF patients.Methods and Results:We prospectively studied 208 ADHF survivors after discharge and divided them into 4 groups according to serum chloride on admission and at discharge: (1) persistent hypochloremia group (n=12), hypochloremia both on admission and at discharge; (2) progressive hypochloremia group (n=42), development of hypochloremia after admission; (3) improved hypochloremia group (n=14), hypochloremia only on admission; and (4) no hypochloremia group, no hypochloremia during hospitalization (n=140). During a mean follow-up period of 1.86±0.76 years, 20 of 208 patients had heart failure death (HFD). In a model adjusted for hyponatremia, hypochloremia both on admission and at discharge was still significantly associated with HFD. Hyponatremia, however, was not significantly associated with HFD after adjustment for hypochloremia. Patients with persistent hypochloremia (HR, 9.13; 95% CI: 2.56-32.55) and with progressive hypochloremia (HR, 4.65; 95% CI: 1.61-13.4) had a significantly greater risk of HFD than those without hypochloremia during hospitalization. CONCLUSIONS: Both persistent hypochloremia and progressive hypochloremia during hospitalization are associated with HFD in ADHF patients.