Hydrogen-Bonded Thiol Undergoes Unconventional Excited-State Intramolecular Proton-Transfer Reactions.

The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone (3NTF) undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm-1. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant nπ* character of the tautomeric lowest excited state. Herein, based on the 3-mercaptoflavone scaffold and π-elongation concept, a new series of 4'-substituted-7-diethylamino-3-mercaptoflavones, NTFs, was designed and synthesized with varied H-bond strength and 690-720 nm tautomeric emission upon ultraviolet (UV) excitation in cyclohexane. The order of their H-bonding strength was experimentally determined to be N-NTF < O-NTF < H-NTF < F-NTF, while the rate of -SH ESIPT measured by fluorescence upconversion was F-NTF (398 fs)-1 < H-NTF (232 fs)-1 < O-NTF (123 fs)-1 < N-NTF (101 fs)-1 in toluene. Unexpectedly, the strongest H-bonded F-NTF gives the slowest ESIPT, which does not conform to the traditional ESIPT model. The results are rationalized by the trend of carbonyl oxygen basicity rather than -SH acidity. Namely, the thiol acidity relevant to the H-bond strength plays a minor role in the driving force of ESIPT. Instead, the proton-accepting strength governs ESIPT. That is to say, the noncanonical thiol H-bonding system undergoes an unconventional type of ESIPT.

Entropy-driven charge-transfer complexation yields thermally activated delayed fluorescence and highly efficient OLEDs.

Exciplex-forming systems that display thermally activated delayed fluorescence are widely used for fabricating organic light-emitting diodes. However, their further development can be hindered through a lack of structural and thermodynamic characterization. Here we report the generation of inclusion complexes between a cage-like, macrocyclic, electron-accepting host (A) and various N-methyl-indolocarbazole-based electron-donating guests (D), which exhibit exciplex-like thermally activated delayed fluorescence via a through-space electron-transfer process. The D/A cocrystals are fully resolved by X-ray analyses, and UV-visible titration data show their formation to be an endothermic and entropy-driven process. Moreover, their emission can be fine-tuned through the molecular orbitals of the donor. Organic light-emitting diodes were fabricated using one of the D/A systems, and the maximum external quantum efficiency measured was 15.2%. An external quantum efficiency of 10.3% was maintained under a luminance of 1,000 cd m-2. The results show the potential of adopting inclusion complexation to better understand the relationships between the structure, formation thermodynamics and properties of exciplexes.

PLI-Based Connectivity in Resting-EEG is a Robust and Generalizable Feature for Detecting MCI and AD: A Validation on a Diverse Multisite Clinical Dataset.

The high prevalence rate of Alzheimer's disease (AD) and mild cognitive impairment (MCI) has been a serious public health threat to the modern society. Recently, many studies have demonstrated the potential of using non-invasive electroencephalography (EEG) and machine learning to assist the diagnosis of AD/MCI. However, the majority of these research recorded EEG signals from a single center, leading to significant concerns regarding the generalizability of the findings in clinical settings. The current study aims to reevaluate the effectiveness of EEG-based machine learning model for the detection of AD/MCI in the case of a relatively large and diverse data set. We collected resting-state EEG data from 150 participants across six hospitals and examined the classification performances of Linear Discriminative Analysis (LDA) classifiers on the phase lag index (PLI) feature. We also compared the performance of PLI over the other commonly-used EEG features and other classifiers. The model was first tested on a training set to select the feature subset and then further validated with an independent test set. The results demonstrate that PLI performs the best compared to other features. The LDA classifier trained with the optimal PLI features can provide 82.50% leave-one-participant-out cross-validation (LOPO-CV) accuracy on the training set and maintain a good enough performance with 75.00% accuracy on the test set. Our results suggest that PLI-based functional connectivity could be considered as a reliable bio-maker to detect AD/MCI in the real-world clinical settings.

Engineering the Macrocyclic Donor Structures towards Deep-Blue Thermally Activated Delayed Fluorescence Emitters.

Deep-blue thermally activated delayed fluorescence (TADF) molecules present promising potential in organic light-emitting diodes (OLEDs), especially for display applications. Here, an efficient molecular engineering approach to modifying the donor or acceptor features of the D-π-A-configured TADF molecules for deep-blue emission is reported. By introducing oxygen and sulfone as a bridge unit onto the macrocyclic donor, two emitters, c-ON-MeTRZ and c-NS-MeTRZ, are synthesized and characterized, respectively. The reduced donor strength of c-ON-MeTRZ and c-NS-MeTRZ as compared to that of the model molecule c-NN-MeTRZ leads to blue-shifted emissions with high photoluminescence quantum yields (PLQYs) and retains TADF characters, while the new emitter c-NN-MePym with the most blue-shifted emission only exhibits a pure fluorescent nature because of the electron-accepting feature of pyrimidine that is insufficient for inducing the TADF property. In the presence of macrocyclic donors, these new emitters show high horizontal dipole ratios (Θ// = 85-89%), which are beneficial for improving the light out-coupling efficiency. Deep-blue TADF OLEDs incorporating c-ON-MeTRZ as an emitter doped in the mCPCN host achieves a high maximum external quantum efficiency (EQEmax) of 30.2% together with 1931 Commission Internationale de I'Eclairage (CIE) coordinates of (0.14, 0.13), while the counter device employing c-NS-MeTRZ as a dopant gives EQEmax of 15.4% and CIE coordinates of (0.14, 0.09). The EQEmax of c-ON-MeTRZ- and c-NS-MeTRZ-based devices can be significantly improved to 34.4 and 29.3%, respectively, with a polar host DPEPO, which stabilizes the charge transfer (CT) S1 state to give lower ΔEST for improving the reverse intersystem crossing process. The efficient TADF character, high PLQYs, and high anisotropic emission dipole ratios work together to render the superior electroluminescence (EL) efficiencies. Based on the detailed characterizations of physical properties, theoretical analyses, and comprehensive study on the corresponding devices, a clear structure-property-performance relationship has been successfully established to verify the effective molecular design strategy of modulating the macrocyclic donor characters for efficient deep-blue TADF emitters.

Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Briavioids E-G, Newly Isolated Briarane-Diterpenoids from a Cultured Octocoral Briareum violaceum.

The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E-G (1-3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1-8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4-8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.

Highly Efficient Singlet Oxygen Generation by BODIPY-Ruthenium(II) Complexes for Promoting Neurite Outgrowth and Suppressing Tau Protein Aggregation.

Singlet oxygen (1O2) has been recently identified as a key molecule against toxic Aß aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)-ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy─an appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.

Pentaleno[1,2-c]pyrroles: Tricyclic 5/5/5 Fused Rings.

A novel method for the preparation of tetrahydropentaleno[1,2-c]pyrroles (8) is described via the reaction of anilines with 1-en-4-yn-3-ols in the presence of Lewis acid. Oxidation of 8 with Br2 gave pentaleno[1,2-c]pyrroles (10), which is the first reported tricyclic 5/5/5 ring with a fully conjugated system. Structures of these obtained compounds were characterized by spectroscopic methods, and compounds 8a,b and 10c were further confirmed by X-ray crystallographic determination.

A linear Di-coordinate boron radical cation.

The pursuit of di-coordinate boron radical has been continued for more than a half century, and their stabilization and structural characterization remains a challenge. Here we report the isolation and structural characterization of a linear di-coordinate boron radical cation, achieved by stabilizing the two reactive atomic orbitals of the central boron atom by two orthogonal π-donating and π-accepting functionalities. The electron deficient radical cation undergoes facile one-electron reduction to borylene and binds Lewis base to give heteroleptic tri-coordinate boron radical cation. The co-existence of half-filled and empty p orbitals at boron also allows the CO-regulated electron transfer to be explored. As the introduction of CO promotes the electron transfer from a tri-coordinate neutral boron radical to a boron radical cation, the removal of CO under vacuum furnishes the reverse electron transfer from borylene to yield a solution consisting of two boron radicals.

Altered coordination between frontal delta and parietal alpha networks underlies anhedonia and depressive rumination in major depressive disorder.

BACKGROUND: A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear. METHODS: We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals. RESULTS: We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination. LIMITATIONS: The sample size was small. CONCLUSION: Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future.

Pd-Promoted Cyclization of (Z)-Pent-2-en-4-yn-1-yl Alkanoates Leading to Furans via an Acyl Group Shift and Further Synthetic Transformation.

Palladium-promoted acyl migration was observed in the reaction of (Z)-pent-2-en-4-yn-1-yl alkanoates in the presence of DBU to yield 2-(alkanoylmethyl)furan derivatives (2) in high yields. Compounds 2 then underwent oxidative decarbonylation to afford 2-acylfurans with O2 as the oxidant under mild and metal-free conditions. The mechanistic pathway of the reaction involving an intramolecular cyclization and acyl group shift is discussed.

An Electric Wheelchair Manipulating System Using SSVEP-Based BCI System.

Most people with motor disabilities use a joystick to control an electric wheelchair. However, those who suffer from multiple sclerosis or amyotrophic lateral sclerosis may require other methods to control an electric wheelchair. This study implements an electroencephalography (EEG)-based brain-computer interface (BCI) system and a steady-state visual evoked potential (SSVEP) to manipulate an electric wheelchair. While operating the human-machine interface, three types of SSVEP scenarios involving a real-time virtual stimulus are displayed on a monitor or mixed reality (MR) goggles to produce the EEG signals. Canonical correlation analysis (CCA) is used to classify the EEG signals into the corresponding class of command and the information transfer rate (ITR) is used to determine the effect. The experimental results show that the proposed SSVEP stimulus generates the EEG signals because of the high classification accuracy of CCA. This is used to control an electric wheelchair along a specific path. Simultaneous localization and mapping (SLAM) is the mapping method that is available in the robotic operating software (ROS) platform that is used for the wheelchair system for this study.

Porous Supramolecular Assembly of Pentiptycene-Containing Gold(I) Complexes: Persistent Excited-State Aurophilicity and Inclusion-Induced Emission Enhancement.

We report herein a porous supramolecular framework formed by a linear mononuclear Au(I) complex (1) via the tongue-and-groove-like joinery between the pentiptycene U-cavities (grooves) and the rod-shaped π-conjugated backbone and alkyl chains (tongues) with the assistance of C-H···π and aurophilic interactions. The framework contains distorted tetrahedral Au4 units, which undergo stepwise and persistent photoinduced Au(I)-Au(I) bond shortening (excited-state aurophilicity), leading to multicolored luminescence photochromism. The one-dimensional pore channels could accommodate different solvates and guests, and the guest inclusion-induced luminescence enhancement (up to 300%) and/or vapochromism are characterized. A correlation between the aurophilic bonding and the luminescence activity is uncovered by TDDFT calculations. Isostructural derivatives 2 and 3 corroborate both the robustness of the porous supramolecular assembly and the mechanisms of the stimulation-induced luminescence properties of 1. This work demonstrates the cooperation of aurophilicity and structural porosity and adaptability in achieving novel supramolecular photochemical properties.

Evaluation of Three Sample Introduction Systems for Impurity Analysis of an Ultrapure Reagent Using a Scanning Mobility Particle Sizer.

The semiconductor industry continues to shrink the device sizes while applying more complex shapes and using diverse materials, which requires parallel improvements in the quality of ultrapure reagents. The need for ultrapure reagents has led to ever-higher demands for the performance of analytical instruments used to detect ultratrace impurities. In this study, nonvolatile impurities in ultrapure reagents were quantified using a scanning mobility particle sizer (SMPS). The performances of three different sample introduction systems, i.e., an electrospray (ES), an aerosol generator with a heating chamber and a Nafion desolvation membrane (NB-II), and a MicroMist nebulizer with a heated cyclonic spray chamber and a three-stage Peltier-cooled desolvation system (MM-APEX), were evaluated for the lower limit of detection of a SMPS. The MM-APEX equipped with the SMPS was able to detect NaCl additives at a concentration of 100 parts per trillion (ppt, ng/L) in ultrapure water, which was approximately 104- and 102-fold lower than those of ES and NB-II, respectively. The practical application of MM-APEX with the SMPS for commercial isopropanol samples was also studied. The results clearly demonstrate that the impurity concentrations presented by the NaCl-equivalent concentrations among different sources of isopropanol were at the ppt to parts-to-billion (ppb) scale. The SMPS system equipped with MM-APEX is capable of recognizing impurities with concentrations ranging from tens ppt to thousands of parts per million (ppm), which is beneficial for an ultratrace analysis of nonvolatile impurities in semiconductor process chemicals.

Palladium-Catalyzed Vinylation of Cyclopentenes with Inverted Z,E-Isomerism of Vinylic Substrates.

A palladium-promoted Mizoroki-Heck type reaction employing a directing-group strategy to efficiently produce the coupled vinyl cyclopentenes with excellent regio- and stereoselectivity is reported. Typically, a Pd-catalyzed reaction of 2-(cyclopent-2-en-1-yl)-N-tosylacetamide (1a) with (E)-styryl bromides gave cis-2-((Z)-styryl)cyclopent-3-en-1-yl-N-tosylacetamide (3e), an allylic substitution product. Interestingly, we have found that the E,Z-stereochemistry of vinylic substrates is inverted in those products. The mechanism of this catalytic reaction is discussed.

Metal-Ion-Induced Mechanical Chirality: Achiral Rotaxane as the Only Ligand in Chiral Palladium(II)-N-Heterocyclic Carbene Complexes.

We report the insertion of Pd(II) into an originally achiral rotaxane producing two chiral metallorotaxanes: one is planar-chiral, with its two interlocked components both chelating nonequivalently to the metal center; the other is C2-symmetrical-chiral, with the dynamically exchangeable stereogenic units stabilized by the interlocked structure. Chiral additives confirmed the existence of chirality, with the enantiomers of the C2-symmetrical N-heterocyclic carbene complex being resolved using chiral TRISPHAT counteranions.

Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles.

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.

Ten-year trends in depression care in Taiwan.

BACKGROUND/PURPOSE: The number of psychiatrists working in community clinics in Taiwan has increased dramatically in the recent decade. This study aimed to investigate the trend of prevalence and incidence of depressive disorders and assess the quality of depression care between 2007 and 2016 in Taiwan. METHODS: We used the claims database derived from Taiwan's National Health Insurance (NHI) program, in which approximately 23.0 million individuals were enrolled, translating to a coverage rate of 99%. Patients with depressive disorders were identified based on International Classification of Diseases codes. The process indicators of depression care quality included visit, duration, and dose adequacy. The outcome indicators included the rate of psychiatric hospitalisation, emergency visit, self-harm hospitalisation, and suicide. RESULTS: The prevalence of treated depressive disorders increased from 1.61% in 2007 to 1.92% in 2016, i.e., a 25% increase, whereas the incidence of first-ever or recurrent depressive disorder did not change significantly. The number of patients treated by psychiatrists and in community clinics also increased. The quality of depression care improved, the proportion of patients receiving minimum psychiatric clinic follow-up and adequate medication increased, and the rate of emergency visits, psychiatric hospitalisation, and self-harm hospitalisation declined. CONCLUSION: The community-based psychiatric services increased and the quality indicators of depression care in Taiwan improved during 2007-2016. The causality warrants further investigations.

Resting-State EEG Signal for Major Depressive Disorder Detection: A Systematic Validation on a Large and Diverse Dataset.

Major depressive disorder (MDD) is a global healthcare issue and one of the leading causes of disability. Machine learning combined with non-invasive electroencephalography (EEG) has recently been shown to have the potential to diagnose MDD. However, most of these studies analyzed small samples of participants recruited from a single source, raising serious concerns about the generalizability of these results in clinical practice. Thus, it has become critical to re-evaluate the efficacy of various common EEG features for MDD detection across large and diverse datasets. To address this issue, we collected resting-state EEG data from 400 participants across four medical centers and tested classification performance of four common EEG features: band power (BP), coherence, Higuchi's fractal dimension, and Katz's fractal dimension. Then, a sequential backward selection (SBS) method was used to determine the optimal subset. To overcome the large data variability due to an increased data size and multi-site EEG recordings, we introduced the conformal kernel (CK) transformation to further improve the MDD as compared with the healthy control (HC) classification performance of support vector machine (SVM). The results show that (1) coherence features account for 98% of the optimal feature subset; (2) the CK-SVM outperforms other classifiers such as K-nearest neighbors (K-NN), linear discriminant analysis (LDA), and SVM; (3) the combination of the optimal feature subset and CK-SVM achieves a high five-fold cross-validation accuracy of 91.07% on the training set (140 MDD and 140 HC) and 84.16% on the independent test set (60 MDD and 60 HC). The current results suggest that the coherence-based connectivity is a more reliable feature for achieving high and generalizable MDD detection performance in real-life clinical practice.