Highly efficient thermally activated delayed fluorescence (TADF) molecules are in urgent demand for solid‐state lighting and full‐color displays. Here, the design and synthesis of three ...triarylamine‐pyridine‐carbonitrile‐based TADF compounds, TPAPPC, TPAmPPC, and tTPAmPPC, are shown. They exhibit excellent photoluminescence quantum yields of 79−100% with small ΔEST values, fast reverse intersystem crossing (RISC), and high horizontal dipole ratios (Θ// = 86−88%) in the thin films leading to the enhancement of device light outcoupling. Consequently, a green organic light‐emitting diode (OLED) based on TPAmPPC shows a high average external quantum efficiency of 38.8 ± 0.6%, a current efficiency of 130.1 ± 2.1 cd A–1, and a power efficiency of 136.3 ± 2.2 lm W–1. The highest device efficiency of 39.8% appears to be record‐breaking among TADF‐based OLEDs to date. In addition, the TPAmPPC‐based device shows superior operation lifetime and high‐temperature resistance. It is worth noting that the TPA‐PPC‐based materials have excellent optical properties and the potential for making them strong candidates for TADF practical application.
Three 2,6‐diphenylpyridine‐3,5‐dicarbonitrile‐based compounds with excellent photoluminescent quantum yields (79–100%) and high horizontal dipole ratios (86−88%) in the thin films are demonstrated. With two methyl groups on the triarylamines, the spin−orbit coupling is enhanced due to the elevated locally excited triplet states (3LE), leading to a fast reverse intersystem crossing. Green thermally activated delayed fluorescence (TADF) organic light‐emitting diodes based on them exhibit a record‐high external quantum efficiency of 39.8% without any optical extraction technique.
The development of high-performance near-infrared organic light-emitting diodes is hindered by strong non-radiative processes as governed by the energy gap law. Here, we show that exciton ...delocalization, which serves to decouple the exciton band from highly vibrational ladders in the S0 ground state, can bring substantial enhancements in the photoluminescence quantum yield of emitters, bypassing the energy gap law. Experimental proof is provided by the design and synthesis of a series of new Pt(ii) complexes with a delocalization length of 5–9 molecules that emit at 866–960 nm with a photoluminescence quantum yield of 5–12% in solid films. The corresponding near-infrared organic light-emitting diodes emit light with a 930 nm peak wavelength and a high external quantum efficiency up to 2.14% and a radiance of 41.6 W sr−1 m−2. Both theoretical and experimental results confirm the exciton–vibration decoupling strategy, which should be broadly applicable to other well-aligned molecular solids.Pt(ii) complexes allow the fabrication of efficient near-infrared organic light-emitting diodes that operate beyond the 900 nm region.
HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.
The ERASE-C Campaign is an ...outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up).
At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.
Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.
NCT03803410 and NCT03891550.
Small extracellular vesicles (sEVs) are important mediators of cell-cell communication with respect to diverse physiological processes. To further understand their physiological roles, understanding ...blood sEV homoeostasis in a quantitative manner is desired. In this study, we propose novel kinetic approaches to estimate the secretion and clearance of mouse plasma-derived sEVs (MP-sEVs) based on the hypothesis that blood sEV concentrations are determined by a balance between the secretion and clearance of sEVs. Using our specific and sensitive sEV labelling technology, we succeeded in analysing MP-sEV clearance from the blood after intravenous administration into mice. This revealed the rapid disappearance of MP-sEVs with a half-life of approximately 7 min. Moreover, the plasma sEV secretion rate, which is presently impossible to directly evaluate, was calculated as 18 μg/min in mice based on pharmacokinetic (PK) analysis. Next, macrophage-depleted mice were prepared as a model of disrupted sEV homoeostasis with retarded sEV clearance. MP-sEV concentrations were increased in macrophage-depleted mice, which probably reflected a shift in the balance of secretion and clearance. Moreover, the increased MP-sEV concentration in macrophage-depleted mice was successfully simulated using calculated clearance rate constant, secretion rate constant and volume of distribution, suggesting the validity of our PK approaches. These results demonstrate that blood sEV concentration homoeostasis can be explained by the dynamics of rapid secretion/clearance.
Near‐infrared organic light‐emitting diodes (NIR OLEDs) enable many unique applications ranging from night‐vision displays and photodynamic therapies. However, the development of efficient NIR OLEDs ...with a low efficiency roll‐off is still challenging. Here, a series of new heteroleptic Pt(II) complexes (1–4) flanked by both pyridyl pyrimidinate and functional azolate chelates are synthesized. The reduced ππ* energy gap of the pyridyl pyrimidinate chelate, and strong intermolecular interaction and high crystallinity in vacuum‐deposited thin films engender strong intermolecular charge transfer transition including metal–metal‐to‐ligand charge transfer; thereby, exhibiting efficient photoluminescence within 776–832 nm and short radiative lifetimes of 0.52–0.79 µs. Consequently, nondoped NIR‐emitting OLEDs based on these Pt(II) complexes are fabricated, to which Pt(II) complexes 2 and 4 give record high maximum external quantum efficiency of 10.61% at 794 nm and 9.58% at 803 nm, respectively. Moreover, low efficiency roll‐off is also observed, among which the device efficiencies of 2 and 4 are at least four times higher than that of the best NIR‐emitting OLEDs recorded at current density of 100 mA cm−2.
Nondoped near‐infrared organic light‐emitting diodes based on pyrimidinate‐pyrazolate Pt(II) metal complexes 2 and 4 are fabricated, yielding a record high maximum external quantum efficiency of 10.61% at 794 nm and 9.58% at 803 nm, respectively.
Flow and turbulent structures generated by the interaction of forced incoming oscillatory flow with a circular, vertical cylinder placed in an open channel with a horizontal bed are investigated ...using eddy-resolving simulations. Validation simulations performed with a Keulegan–Carpenter (KC) number of 20 and multiple-mode forcing corresponding to the laboratory experiment of Sumer et al. (J. Fluid Mech., vol. 332, 1997, pp. 41–70) show that detached eddy simulation (DES) predicts more accurately the amplification of the bed shear stress beneath the horseshoe vortex system (upstream side of the cylinder) and the maximum magnitude of the bed shear stress at the downstream (wake) side of the cylinder compared with unsteady Reynolds-averaged Navier–Stokes simulations. High-Reynolds-number DES simulations are then conducted with 1.5 ≤ KC ≤ 30.8 and one-mode sinusoidal forcing of the streamwise velocity in the approaching flow to investigate the changes in the wake vortex-flow regimes, the coherence of the horseshoe vortices and the generation of other near-bed coherent structures in the wake during the oscillatory cycle. The flow is periodic, no horseshoe vortices form and no vortices are shed in the wake for KC = 1.5. By contrast, for KC ≥ 8 horseshoe vortices are present over part of the oscillatory cycle and up to three wake vortices are shed over each half-cycle as KC is increased to 30.8. For an intermediate range of KC numbers, one (KC = 15.4) or two (KC = 8) of the vortices forming at the back of the cylinder during each half-cycle are washed around it when the flow reverses. The main horseshoe vortex and other horizontal near-bed vortices have a large capacity to amplify the bed shear stresses when the incoming velocity magnitude is significantly less than its peak value. Assuming the depth-averaged velocity in the incoming (undisturbed) oscillatory flow is the same in simulations conducted with different KC numbers, the peak values of the sediment entrainment potential measured by the mean (cycle-averaged) volumetric flux of sediment entrained from the bed over one oscillatory cycle occur for 8 ≤ KC ≤ 15.4. For all KC numbers, the in-line force variation over the oscillatory cycle is fairly well approximated by the Morison equation. For KC = 1.5, the in-line force is only due to inertia effects. For KC = 30.8, the maximum and minimum values of the phase-averaged in-line force are approximatively in phase with those of the incoming flow velocity. For KC ≥ 15, the phase-averaged in-line force coefficients vary between 0.8 and 1.1 during most of the oscillatory cycle (e.g. when the incoming flow velocity is not close to zero). This is different from cases with KC ≤ 8 where the in-line force coefficient is equal to zero twice during the oscillatory cycle as the in-line force becomes equal to zero for non-zero values of the incoming velocity. The largest cycle-to-cycle variations of the in-line force coefficient and in-line force are observed around KC = 8. For KC = 8 and 15.4, the cylinder is subject to relatively large phase-averaged spanwise drag forces that are comparable to the peak phase-averaged streamwise drag forces. As KC is increased to 30.8, the phase-averaged spanwise drag force becomes zero over the whole oscillatory cycle but the cylinder is still subject to large instantaneous spanwise forces over part of the oscillatory cycle.
Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 ...can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.
Objective:
In this study, we intended to evaluate whether swallow treatment with neuromuscular electrical stimulation is superior to that without neuromuscular electrical stimulation, and whether ...neuromuscular electrical stimulation alone is superior to swallow therapy.
Methods:
We searched the PubMed and Scopus databases from their earliest record to 31 December 2014 for randomized and quasi-randomized controlled trials that used neuromuscular electrical stimulation to treat post-stroke dysphagia. The Jadad scale was used to assess the quality of the included studies. We extracted the mean differences and standard deviation (SD) between baseline and posttreatment or posttreatment mean and SD for selected outcomes measured in the experimental and control groups for subsequent meta-analyses.
Results:
Eight studies were identified. For the comparison “swallow treatment with neuromuscular electrical stimulation vs. swallow treatment without neuromuscular electrical stimulation,” we found a significant standardized mean difference (SMD) of 1.27 (95% confidence interval (CI) = 0.51–2.02, P = 0.001) with significant heterogeneity (I2 = 85%). The meta-analysis for the comparison of neuromuscular electrical stimulation alone and swallow therapy demonstrated a non-significant SMD of 0.25 (95% CI = –0.16–0.65, P = 0.23) without significant heterogeneity (I2 = 16%).
Conclusion:
Swallow treatment with neuromuscular electrical stimulation seems to be more effective than that without neuromuscular electrical stimulation for post-stroke dysphagia in the short term considering the limited number of studies available. Evidence was insufficient to indicate that neuromuscular electrical stimulation alone was superior to swallow therapy.
Epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived ...mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133
/CD83
cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation. Then, tumor-tropic BM-MSCs circulated to primary sites and triggered CD151
/CD38
cells acquiring EMT-associated CSC properties through IL6R/pY705-STAT3 signaling to promote tumor initiation and were also attracted by and migrated towards the premetastatic niche. In summary, STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates the EMT-MET switch within the distinct molecular subtypes of CSCs to complete the metastatic process.
It is often helpful to classify biomarker values into groups of different risk levels to facilitate evaluation of a biological, physiological, or pathological state. Stratification of patients into ...two risk groups is commonly seen, but there is always need for more than two groups for fine assessment. So far, there are no standard methods or tools to help decide how many cutoff points are optimal. In this study, we developed a comprehensive package that included methods to determine both the optimal number and locations of cutoff points for both survival data and dichotomized outcome. We illustrated workflow of this package with data from 797 patients with cervical cancer. By analyzing several risk factors of cervical cancer such as tumor size, body mass index (BMI), number of lymph nodes involved and depth of stromal invasion, in relation to survival and clinical outcome such as lymph nodal metastasis and lymphovascular invasion, we demonstrated that the best choice for BMI and stromal invasion was two cutoff points and one for the others. This study provided a useful tool to facilitate medical decisions and the analyses on cervical cancer may also be of interest to gynecologists. The package can be freely downloaded.
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