Microscopic vibrational circular dichroism on the forewings of a European hornet: heterogenous sequences of protein domains with different secondary structures.

We developed a microscopic scanning for vibrational circular dichroism (VCD) spectroscopy in which a quantum cascade laser is equipped with a highly focused infrared light source to attain a spatial resolution of 100 µm. This system was applied to the forewing of a European hornet to reveal how the protein domains are organised. Two-dimensional patterns were obtained from the VCD signals with steps of 100 µm. We scanned the 1500-1740 cm-1 wavenumber range, which covers amide I and II absorptions. Zone sequenced α-helical and ß-sheet domains within an area of 200 µm2 in membranes close to where two veins cross. The sign of the VCD signal at 1650 cm-1 changed from positive to negative when probed along the zone axis, intermediated by the absence of VCD activity. The significance of this zone is discussed from the viewpoint of the mechanical properties required for flying motion. These features are unattainable using conventional FTIR (Fourier transform infrared) or FT-VCD methods with a spatial resolution of ∼10 mm2.

Association between preoperative white matter hyperintensities and postoperative new ischemic lesions on magnetic resonance imaging in patients with cognitive decline after carotid endarterectomy.

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78-28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42-571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA.

Prediction of spontaneous echocardiographic contrast within the left atrial appendage in cardiac computed tomography of patients with atrial fibrillation.

This study aimed to assess the predictors of spontaneous echocardiographic contrast (SEC) using left atrial appendage (LAA) findings in cardiac computed tomography (CT) of patients with atrial fibrillation (AF). We retrospectively analyzed cardiac CT findings of the LAA, including morphology, volume, and filling defects, of 641 patients who underwent transesophageal echocardiography (TEE) prior to pulmonary vein isolation (PVI) from January 6, 2013 through December 16, 2019 at our institution. We investigated potential associated factors that might be predictors of SEC using cardiac CT findings and computed a receiver operator characteristic, choosing a threshold value at which the likelihood of SEC could be predicted based on the LAA volume indexed for body size. SEC correlated significantly with indexed LAA volume (P < 0.001; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.17-1.48) of 7.75 cm3/m2 or greater (sensitivity, 76.0%; specificity, 57.7%), LAA early filling defect (P = 0.005; OR, 2.72; 95% CI, 1.35-5.48), a history of persistent AF (P < 0.001; OR, 3.81; 95% CI, 1.86-7.80), and LAA flow velocity (P < 0.001; OR, 0.97; 95% CI, 0.96-0.99). Findings of LAA in cardiac CT can allow for the noninvasive estimation of SEC to determine the need for additional TEE investigation and the need to obtain additional information for risk stratification and management of thromboembolic events in patients with AF.

Computed tomography findings associated with the reduction in left atrial appendage flow velocity in patients with atrial fibrillation.

The reduction in flow velocity within the left atrial appendage (LAAFV) is associated with a high risk of thromboembolic events. There has been few reports using sufficient sample size about the relationship between LAAFV reduction and LAA features on cardiac computed tomography (CT), including LAA volume and filling defects, in patients with atrial fibrillation (AF). We evaluated the predictors of reduced flow velocity within the LAA using the findings of cardiac CT in patients with AF. We retrospectively analysed the cardiac CT findings of the LAA of 440 patients who underwent transoesophageal echocardiography prior to pulmonary vein isolation between 12 February, 2013 and 16 December, 2019 at our institution. We investigated the potential predictors of reduced LAAFV and the difference in LAAFV between the different morphological types of the LAA. The reduced flow velocity within the LAA was significantly correlated with higher CHADS2 scores [P = 0.001; odds ratio (OR), 1.52; 95% confidence interval (CI), 1.18-1.95], early filling defect in the LAA (P = 0.001; OR, 3.36; 95% CI 1.63-6.93), and increased indexed LAA volume (P = 0.036; OR, 1.09; 95% CI 1.01-1.19). The LAA morphological type and AF type were not significant predictors of the LAAFV reduction. Increased LAA volume, early filling defects in the LAA, and higher CHADS2 scores were independent predictors of LAAFV reduction in patients with AF. Our findings suggest that cardiac CT findings might allow non-invasive estimation of reduced LAAFV. These CT-derived parameters may provide additional information for the risk stratification and management of thromboembolic events in patients with AF.

Multidimensional Vibrational Circular Dichroism Apparatus Equipped with Quantum Cascade Laser and Its Use for Investigating Some Peptide Systems Containing d-Amino Acids.

We developed a multidimensional vibrational circular dichroism system with a positional coordinate, making it possible to move in both x- and y-directions using an automatic stage. Quantum cascade laser (QCL) was used as a light source to achieve high intensity and narrow focusing. The QCL emitted light in the wavenumber range of 1500-1740 cm-1, which encompassed absorption bands assigned to the stretching vibrations of amides I and II. The operation of the instrument was analyzed for samples containing amide groups. An aqueous solution of Gly-l-Leu or Gly-d-Leu was measured under the background absorbance as high as 3.5 due to the water medium. The spectra were recorded by scanning at 1.0 cm-1 steps. The time required for performing measurement at each wavenumber was less than 1 s. The mirror-image relation was maintained between the optical antipodes. A peak assigned to amide II appeared clearly at around 1580 cm-1. In the case of KBr pellets containing the same compounds, peaks assigned to amide I and II were observed. For two-dimensional pattering, a KBr pellet comprising two domains of amino acids (or l-Ala and d-Ser) was investigated. The distribution of each component within the pellet was obtained under the two-dimensional alignment at the spatial interval of 2.5 mm.

HOMO-LUMO Energy-Gap Tuning of π-Conjugated Zwitterions Composed of Electron-Donating Anion and Electron-Accepting Cation.

π-Conjugated molecules with small highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps (ΔEH-L) have been extensively studied because of their unique optoelectronic properties. Although the expansion of π-conjugation is one of the well-known approaches for designing molecules with small ΔEH-L values, such an approach inevitably gives large π-conjugated molecules sometimes suffering from synthetic difficulty and low solubility toward organic solvents. To develop relatively small donor-acceptor molecules with small ΔEH-L values, we have designed and synthesized π-conjugated zwitterions composed of electron-donating anions, such as phenoxide and anthroxide, and electron-accepting cations, such as pyridinium and acridinium. The energy difference between the HOMO of the anion and the LUMO of the cation (ΔED-A) and the interplanar angle between them (φDA) have a crucial effect on ΔEH-L, and hence, on the electronic structures and optoelectronic properties of these zwitterions. The zwitterions with small ΔED-A and large φDA have a small ΔEH-L of ca. 1 eV and show amphoteric redox properties and near-infrared (NIR) electronic absorption exceeding λ = 1000 nm. The NIR absorption responds to solvent polarity, temperature, and acid addition. This molecular design will generate small π-conjugated donor-acceptor molecules with small ΔEH-L values.

Impact of Percutaneous Edge-to-Edge Repair in Patients With Atrial Functional Mitral Regurgitation.

BACKGROUND: The aim of this study was to clarify the clinical outcomes of patients with atrial functional mitral regurgitation (FMR) who underwent the MitraClip procedure compared with those with conventional FMR and sinus rhythm (SR).Methods and Results:Of 303 patients with FMR who underwent the MitraClip procedure, 40 with "atrial-FMR" defined as FMR with permanent atrial fibrillation and normal left ventricular (LV) function/size and 115 with "sinus-FMR" defined as FMR with SR and LV dysfunction were reviewed. Transthoracic and 3D transesophageal echocardiography, and the cardiac complication rate (composite of all-cause death, heart failure admission, mitral valve (MV) surgery, and redo MitraClip procedure) during the 12-month follow-up were compared between the groups. After the MitraClip procedure, reductions in the mitral annular area and its anteroposterior dimension and in the leaflet closure area were observed in both groups. MV orifice area was smaller with greater transmitral pressure gradient (P<0.05) after the procedure in atrial-FMR patients than in those with sinus-FMR. The prevalence of residual MR was similar, but significant tricuspid regurgitation (TR) was more prevalent in the atrial-FMR group at follow-up. Cardiac complication rate was comparable between groups (20% vs. 25%, P=0.63). CONCLUSIONS: Reduction of MR occurred in atrial-FMR probably because of the increase in leaflet coaptation area. Significant TR was more common after the MitraClip procedure in patients with atrial-FMR than with sinus-FMR. However, mid-term outcomes were comparable between patients with atrial-FMR and sinus-FMR.

Left ventricular outflow tract area after percutaneous transseptal transcatheter mitral valve implantation: A three-dimensional transesophageal echocardiography study.

BACKGROUND: Left ventricular (LV) outflow tract (LVOT) obstruction increases mortality in patients undergoing transcatheter mitral valve implantation (TMVI) in degenerated bioprostheses, annuloplasty rings, and native mitral valves. We aimed to evaluate the LVOT area after TMVI using 3-dimensional (3D) transesophageal echocardiography (TEE) and to investigate the preprocedural cardiac geometry that affects the LVOT area after TMVI. METHODS: We retrospectively reviewed echocardiography data in 43 patients who had TMVI. A change in pressure gradient across LVOT from before to after TMVI (∆PG) and postprocedure 3D LVOT cross-sectional area at the level of the most distal portion of the mitral valve stent that was closest to the LV apex were assessed as evidence of LVOT narrowing. RESULTS: Transcatheter mitral valve implantation with the use of balloon-expandable valve system was performed for 24 bioprostheses, 7 annuloplasty rings, and 12 native valves. Compared to patients without increase in LVOT gradient (∆PG <10 mm Hg; n = 33), patients with increase in LVOT gradient (∆PG ≥10 mm Hg; n = 10) had smaller LV end-systolic volume (LVESV), greater LV ejection fraction (LVEF), and smaller aorto-mitral (AM) angle. The LVOT area at the valve stent distal edge showed strong association with ∆PG (r = -.68, P < .0001). Only a small AM angle was associated with a small LVOT area at the valve stent distal edge on multivariable analysis, independent of LVESV and LVEF. CONCLUSION: Small LV size, preserved LVEF, and small AM angle were associated with LVOT narrowing. 3D-derived AM angle might be independently associated with LVOT narrowing in patients undergoing transcatheter mitral valve-in-valve, valve-in-ring, and valve-in-native valve implantation, independent of LVESV and LVEF.

Metal-Free Twofold Electrochemical C-H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis.

The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non-protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C-N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against castrate-resistant prostate cancer. Further improvement of the structure led to significantly increased cancer cell line toxicity. Thus, exploiting environmentally benign electrooxidation, we present a new versatile and powerful method based on direct C-H activation that is applicable for example the production of medicinally relevant compounds.

Electrogenerated Cationic Reactive Intermediates: The Pool Method and Further Advances.

Electrochemistry serves as a powerful method for generating reactive intermediates, such as organic cations. In general, there are two ways to use reactive intermediates for chemical reactions: (1) generation in the presence of a reaction partner and (2) generation in the absence of a reaction partner with accumulation in solution as a "pool" followed by reaction with a subsequently added reaction partner. The former approach is more popular because reactive intermediates are usually short-lived transient species, but the latter method is more flexible and versatile. This review focuses on the latter approach and provides a concise overview of the current methods for the generation and accumulation of cationic reactive intermediates as a pool using modern techniques of electrochemistry and their reactions with subsequently added nucleophilic reaction partners.

Vibrational circular dichroism towards asymmetric catalysis: chiral induction in substrates coordinated with copper(II) ions.

Cu(ii) complexes containing RR- or SS-2,2'-isopropylidene-bis(4-phenyl-2-oxazoline) (denoted as [Cu(RR- or SS-oxa)]2+) are known to catalyse many asymmetric organic reactions. Herein, the source of enantioselectivity was investigated by vibrational circular dichroism (VCD) spectroscopy. An achiral ß-diketonato ligand (denoted as LH), such as 1-phenyl-1,3-butanedione and dibenzoylmethane, was added to form [Cu(RR- or SS-oxa)L]+. Clear VCD peaks were obtained from a CDCl3 solution of [Cu(RR- or SS-oxa)]2+ or [Cu(RR- or SS-oxa)L]+ at 1000-1800 cm-1. It is to be noted that when LH was coordinated, a new VCD peak appeared at ∼1380 cm-1, which was assigned to the C-O asymmetric stretching vibration of L-. Theoretical simulation helped rationalise the results in terms of the transformation of coordinated L- into a twisted chiral form. The extent of steric control within the coordination sphere was demonstrated, revealing the first step for enantioselectivity during catalysis.

Identification of the Distal End of Carotid Plaque Using 3-Dimensional Fast Spin Echo T1-Weighted Magnetic Resonance Plaque Imaging.

BACKGROUND: Complete removal of the distal end of the plaque is an important requirement in carotid endarterectomy (CEA) to avoid postoperative complication. Preoperative identification of the distal end of plaque contributes to complete plaque removal. Three-dimensional (3D) magnetic resonance (MR) plaque imaging has been widely used to evaluate carotid plaque characterization. The purpose of the present study was to determine whether preoperative 3D fast spin echo (FSE) T1-weighted MR plaque imaging could identify the distal end of carotid plaque. METHODS: This study was designed as a prospective cohort study. We examined 50 patients with cervical internal carotid artery (ICA) stenosis who underwent CEA. 3D-FSE T1-weighted MR plaque imaging of the affected carotid bifurcation was preoperatively performed using a 1.5-T scanner. Identification of the distal end of plaque (DEMRI) on MR plaque imaging was performed and the distance from the baseline (DistanceMRI) was measured. Intraoperatively, the superimposed distal end of carotid plaque (Esim) was marked on the ICA according to the measurement on MR plaque imaging. The actual distal end of plaque (DECEA) was then identified after arteriotomy and the difference (DifferenceCEA-MRI) between Esim and DECEA was measured. Contrast ratio of carotid plaque and tortuosity of the ICA were calculated using MR plaque imaging. RESULTS: Interobserver agreements in measurement of DistanceMRI were excellent (intraclass correlation coefficient, .955; 95% confidence interval, .922-.974). In 28 patients (56%), Esim was identical to DECEA. Mean DifferenceCEA-MRI was 1.32 ± 1.77 mm. DifferenceCEA-MRI was significantly greater with fibrotic plaque (4.14 ± 1.21 mm) than with lipid-rich or necrotic plaque (.43 ± .87 mm; P < .05) or hemorrhagic plaque (1.27 ± 1.64 mm; P < .05). Mean DifferenceCEA-MRI was significantly greater in the group with tortuosity of the ICA less than 120° (3.86 ± 1.77 mm) than in the group with greater than or equal to 120° but less than or equal to 150° (1.15 ± 1.51 mm; P < .05) or greater than150° (0.50 ± 1.10 mm; P < .05). No patients showed residual stenosis after surgery on postoperative MR angiography. CONCLUSIONS: Using 3D-FSE T1-weighted MR plaque imaging allowed identification of the distal end of carotid plaque and contributed to complete removal of the plaque, although it may be reduced for cases with low-signal-intensity plaque or severe tortuosity of the ICA.

A Novel Approach to Functionalization of Aryl Azides through the Generation and Reaction of Organolithium Species Bearing Masked Azides in Flow Microreactors.

A novel straightforward method for aryl azides having functional groups based on generation and reactions of aryllithiums bearing a triazene group from polybromoarenes using flow microreactor systems was achieved. The present approach will serve as a powerful method in organolithium chemistry and open a new possibility in the synthesis of polyfunctional organic azides.

Oxo-Thiolation of Cationically Polymerizable Alkenes Using Flow Microreactors.

The present study describes the cationic oxo-thiolation of polymerizable alkenes by using highly reactive cationic species generated by anodic oxidation. These highly reactive cations were able to activate alkenes before their polymerization. Fast mixing in flow microreactors effectively controlled chemoselectivity, enabling higher reaction temperatures.

Generation and Reaction of Functional Alkyllithiums by Using Microreactors and Their Application to Heterotelechelic Polymer Synthesis.

Flow microreactors enabled the successful generation of various functional alkyllithiums containing electrophilic functional groups, as well as the use of these alkyllithiums in subsequent reactions. The high reactivity of these series of reactions could be achieved by the extremely accurate and selective control of residence time. Moreover, integrated flow microreactor systems could be used to successfully synthesize heterotelechelic polymers with two functionalities, one at each end, via a process involving controlled anionic polymerization initiated by functional alkyllithium compounds, followed by trapping reactions with difunctional electrophiles.

Synthesis of Functionalized Ketones from Acid Chlorides and Organolithiums by Extremely Fast Micromixing.

Synthesis of ketones containing various functional groups from acid chlorides bearing electrophilic functional groups and functionalized organolithiums was achieved using a flow microreactor system. Extremely fast mixing is important for high chemoselectivity.

Competing forces in the self-assembly of amide-functionalized discotic mesogens.

The effect of incorporating a single amide group on the self-assembly of discotic mesogens was examined. Two series of tetraalkoxydibenzophenazines amides were prepared: tertiary diethyl amides, dEt(n) incapable of hydrogen bonding, and secondary amides HBu(n) that can act as both H-bond donors and acceptors. These compounds exhibit markedly different behavior in solution; NMR studies of dEt(n) show no evidence of self-association, whereas HBu(n) strongly associate via H-bonding and π-stacking. Compounds HBu(n) also act as small molecule gelators in a range of solvents, a property not observed for the corresponding tertiary amides. All compounds were found to form Colh liquid crystal phases; variable temperature XRD experiments indicate that each column has a diameter approximately equal to that of a single molecule. A comparison of the phase behavior of HBu(n) and dEt(n) suggests that the columnar phases of the former are stabilized by hydrogen bonding, likely at the expense of local parallel alignment of these molecules. Single crystal X-ray diffraction studies revealed that dEt(6) adopts an antiparallel arrangement in the solid state, in keeping with previous theories of packing within columnar LC phases. These studies highlight the interplay between competing factors, such as hydrogen bonding, π-stacking and dipole-dipole interactions that affect the stability of the LC phases.

Alkyllithium Compounds Bearing Electrophilic Functional Groups: A Flash Chemistry Approach.

Flash chemistry based on flow microreactor systems allowed alkyllithiums bearing electrophilic functional groups to be successfully generated and used for subsequent reactions. The series of reactions with high reactivity was achieved by extremely accurate control over residence time in a controlled and selective manner.

Scaling Law for Three-Body Collisions of Identical Fermions with p-Wave Interactions.

We experimentally confirmed the threshold behavior and scattering length scaling law of the three-body loss coefficients in an ultracold spin-polarized gas of ^{6}Li atoms near a p-wave Feshbach resonance. We measured the three-body loss coefficients as functions of temperature and scattering volume, and we found that the threshold law and the scattering length scaling law hold in limited temperature and magnetic field regions. We also found that the breakdown of the scaling laws is due to the emergence of the effective-range term. This work is an important first step towards a full understanding of the loss of identical fermions with p-wave interactions.

Ca2+-Signal Transduction Inhibitors, Kujiol A and Kujigamberol B, Isolated from Kuji Amber Using a Mutant Yeast.

A podocarpatriene and a labdatriene derivative, named kujiol A [13-methyl-8,11,13-podocarpatrien-19-ol (1)] and kujigamberol B [15,20-dinor-5,7,9-labdatrien-13-ol (2)], respectively, were isolated from Kuji amber through detection with the aid of their growth-restoring activity against a mutant yeast strain ( zds1Δ erg3Δ pdr1Δ pdr3Δ), which is known to be hypersensitive with respect to Ca2+-signal transduction. The structures were elucidated by spectroscopic data analysis. Compounds 1 and 2 are rare organic compounds from Late Cretaceous amber, and the mutant yeast used seems useful for elucidating a variety of new compounds from Kuji amber specimens, produced before the K-Pg boundary.