The triad types of molecules with various combinations of electron donors (D) and acceptors (A) have been widely explored in optoelectronics. However, their photophysical and photochemical ...properties, which are frequently unconventional, are relatively unexplored. In this study, a donor–donor–acceptor (D–D–A)-type triad, CTPS, consisting of the donor moiety of triphenylamine (D1) and the acceptor moiety of dibenzothiophene sulfone (A) bridging through the second donor carbazole (D2) into a U-shape configuration, was synthesized. CTPS exhibited dual emission bands, both of which reveal solvent-polarity-dependent solvatochromism and unusual excitation-wavelength-dependent ratiometric emission. Comprehensive studies clarified that two emissions originate from two different D–A charge-transfer (CT) states. The lower-energy CT(S) state possesses D1 → A through-space CT nature with optically forbidden transition, whereas the higher-lying CT(B) state is associated with optically allowed D2 → A CT through the π-conjugation transition. Upon S0 → CT(B) excitation, the charge transfer creates D2δ+Aδ− dipolar changes and Aδ−–D1 repulsion, leading to structural relaxation of the CT(B) state that competes with fast CT(B) → CT(S) internal conversion. Therefore, despite the fact that they originate from the same Franck–Condon excited state, both energy-stabilized CT(B) and CT(S) states are populated through two independent channels. The stabilized CT(B) and CT(S) states possess different optimized geometries and do not interconvert during their lifespans, rendering different population decay time constants. The slim highest occupied molecular orbital/lowest unoccupied molecular orbital overlapped D1–A CT(S) state exhibits thermally activated delayed fluorescence (TADF), the character of which was further exploited as a host in organic light-emitting diode. The results gain new insights into the properties of the bending-type D–D–A TADF triads. CTPS should not be a unique case. Bizarre photophysical behavior encountered in molecules comprising multiple D and A groups may involve the interplay among various local CT states, which might have been overlooked.
Measurement-device-independent quantum key distribution (MDI-QKD) can eliminate all detector side channels and it is practical with current technology. Previous implementations of MDI-QKD all used ...two symmetric channels with similar losses. However, the secret key rate is severely limited when different channels have different losses. Here we report the results of the first high-rate MDI-QKD experiment over asymmetric channels. By using the recent 7-intensity optimization approach, we demonstrate>10×higher key rate than the previous best-known protocols for MDI-QKD in the situation of large channel asymmetry, and extend the secure transmission distance by more than 20-50 km in standard telecom fiber. The results have moved MDI-QKD towards widespread applications in practical network settings, where the channel losses are asymmetric and user nodes could be dynamically added or deleted.
Abstract
Alternative Lengthening of Telomeres (ALT) utilizes a recombination mechanism and break-induced DNA synthesis to maintain telomere length without telomerase, but it is unclear how cells ...initiate ALT. TERRA, telomeric repeat-containing RNA, forms RNA:DNA hybrids (R-loops) at ALT telomeres. We show that depleting TERRA using an RNA-targeting Cas9 system reduces ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interactome reveals that TERRA interacts with an extensive subset of DNA repair proteins in ALT cells. One of TERRA interacting proteins, the endonuclease XPF, is highly enriched at ALT telomeres and recruited by telomeric R-loops to induce DNA damage response (DDR) independent of CSB and SLX4, and thus triggers break-induced telomere synthesis and lengthening. The attraction of BRCA1 and RAD51 at telomeres requires XPF in FANCM-deficient cells that accumulate telomeric R-loops. Our results suggest that telomeric R-loops activate DDR via XPF to promote homologous recombination and telomere replication to drive ALT.
Objectives
This study aimed to assess the comparative efficacy of four ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3‐year ...follow‐up in patients with persistent AF.
Background
The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear.
Methods
Patients with persistent AF were enrolled consecutively to undergo each of four ablation strategies: (a) Group 1 (Gp 1, n = 69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n = 75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n = 42), PVI plus the elimination of complex fractionated atrial electrograms; (d) Gp 4 (n = 67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model.
Results
Baseline characteristics were similar across the four groups. At a follow‐up period of 34.9 ± 38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other three groups (p = .002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p = .006). Independent predictors of recurrence of AF were the ablation strategy (p = .002) and left atrial diameter (LAD) (p = .01).
Conclusion
In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared with the other strategies. Both ablation strategy and baseline LAD predicted the 3‐year outcomes of freedom from AT/AF
Insufficient exercise affects the health of patients who have implantable cardioverter defibrillators (ICD). The purpose of this study was to investigate the correlations between exercise ...self-efficacy (ESE) and its associated psychological factors in ICD recipients. This cross-sectional study included individuals who had undergone ICD implantation at the cardiology department of a medical centre in Taiwan. A face-to-face survey was conducted. The survey questionnaire included questions regarding the participants' demographics, perceived health (PH), ICD shock-related anxiety (ICD-SRA), self-care self-efficacy (SSE), perceived exercise benefit (PE-benefit), perceived exercise barrier (PE-barrier), and ESE. Data were analysed using SPSS 20.0 Software. Stepwise multiple regression analyses were also performed to evaluate the predictive effects of the aforementioned factors on ESE. A total of 52 ICD recipients were enrolled. ESE was negatively correlated with ICD-SRA (r = -0.511; p < 0.01) and PE-barrier (r = -0.563; p < 0.01), but positively correlated with SSE (r = 0.339; p < 0.05) and PE-benefit (r = 0.464; p < 0.01). The stepwise multiple regression analysis revealed that PE-barrier, PE-benefit, and ICD-SRA effectively predicted ESE in the participants. ESE may be improved by overcoming PE-barrier, ICD-SRA and enhancing PE-benefit. Consequently, improving ESE may enhance the health benefits of exercise.
It is increasingly popular to collect as much data as possible in the hospital setting from clinical monitors for research purposes. However, in this setup the data calibration issue is often not ...discussed and, rather, implicitly assumed, while the clinical monitors might not be designed for the data analysis purpose. We hypothesize that this calibration issue for a secondary analysis may become an important source of artifacts in patient monitor data. We test an off-the-shelf integrated photoplethysmography (PPG) and electrocardiogram (ECG) monitoring device for its ability to yield a reliable pulse transit time (PTT) signal.
This is a retrospective clinical study using two databases: one containing 35 subjects who underwent laparoscopic cholecystectomy, another containing 22 subjects who underwent spontaneous breathing test in the intensive care unit. All data sets include recordings of PPG and ECG using a commonly deployed patient monitor. We calculated the PTT signal offline.
We report a novel constant oscillatory pattern in the PTT signal and identify this pattern as a sawtooth artifact. We apply an approach based on the de-shape method to visualize, quantify and validate this sawtooth artifact.
The PPG and ECG signals not designed for the PTT evaluation may contain unwanted artifacts. The PTT signal should be calibrated before analysis to avoid erroneous interpretation of its physiological meaning.
Introduction
We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first‐attempt endocardial ablation in patients with ...nonparoxysmal atrial fibrillation (AF).
Methods and Results
Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug‐refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation PVI, substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity‐matched analysis (N = 128) of long‐term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio HR, 4.17; 95% confidence interval 95% CI, 1.63‐10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09‐3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16‐5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08‐0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17‐0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups.
Conclusion
Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long‐term freedom from AF and atrial arrhythmia.
Targeted delivery of drugs to tumors represents a significant advance in cancer diagnosis and therapy. Therefore, development of novel tumor-specific ligands or pharmaceutical nanocarriers is highly ...desirable. In this study, we utilized phage display to identify a new targeting peptide, SP90, which specifically binds to breast cancer cells, and recognizes tumor tissues from breast cancer patients. We used confocal and electron microscopy to reveal that conjugation of SP90 with liposomes enables efficient delivery of drugs into cancer cells through endocytosis. Furthermore, in vivo fluorescent imaging demonstrated that SP90-conjugated quantum dots possess tumor-targeting properties. In tumor xenograft and orthotopic models, SP90-conjugated liposomal doxorubicin was found to improve the therapeutic index of the chemotherapeutic drug by selectively increasing its accumulation in tumors. We conclude that the targeting peptide SP90 has significant potential in improving the clinical benefits of chemotherapy in the treatment and the diagnosis of breast cancer.
Inflammation is a critical defense mechanism that is utilized by the body to protect itself against pathogens and other noxious invaders. However, if the inflammatory response becomes exaggerated or ...uncontrollable, its original protective role is not only demolished but it also becomes detrimental to the affected tissues or even to the entire body. Thus, regulating the inflammatory process is crucial to ensure that it is resolved promptly to prevent any subsequent damage. The role of neutrophils in inflammation has been highlighted in recent decades by a plethora of studies focusing on neutrophilic inflammatory diseases as well as the mechanisms to regulate the activity of neutrophils during the overwhelmed inflammatory process. As natural products have demonstrated promising effects in a wide range of pharmacological activities, they have been investigated for the discovery of new anti-inflammatory therapeutics to overcome the drawbacks of current synthetic agents. Octocorals have attracted scientists as a plentiful source of novel and intriguing marine scaffolds that exhibit many pharmacological activities, including anti-inflammatory effects. In this review, we aim to provide a summary of the neutrophilic anti-inflammatory properties of these marine organisms that were demonstrated in 46 studies from 1995 to the present (April 2023). We hope the present work offers a comprehensive overview of the anti-inflammatory potential of octocorals and encourages researchers to identify promising leads among numerous compounds isolated from octocorals over the past few decades to be further developed into anti-inflammatory therapeutic agents.
Biscembranoids are the distinctive tetraterpenoids owing a 14/6/14 membered tricyclic scaffold that have been mainly discovered in the soft corals, especially the genera
,
and
. Recent findings have ...demonstrated the great anti-inflammatory potential of biscembranoid analogues in human neutrophils, motivating more chemical and biological explorations targeting these marine-derived natural products. In the current study, the chemical diversity of biscembranoids derived from the cultured-type
von Marenzeller was illustrated through MS/MS molecular networking (MN) profiling approach. Based on the MN patterns, the prioritization of unknown biscembranoid derivatives was putatively analyzed. As a result, the biscembrane targeting isolation afforded two new metabolites, sarcotrochelides A (
) and B (
), along with six known analogues (
-
). Their structures and relative configurations were determined by spectroscopic methods. In vitro neutrophil inflammatory inhibition was further investigated for all isolates based on reduced superoxide anion (O
) generation detections. Compounds
-
showed significant dose-dependently inhibitory effects, suggesting the cruciality of 6,7-dihydrooxepin-2(5H)-one moiety and saturated γ-lactone ring in their reactive oxygen species (ROS)-dependent anti-inflammatory properties.
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