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.
The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a ...matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC.
This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18–70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up.
Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0–69·0), 74 patients had died (29 29% of 100 patients in the ENPG group and 45 45% of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9–92·7) in the ENPG group and 68·0% (58·6–77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29–0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five 5% of 99 patients who underwent ENPG and 26 26% of 101 patients who underwent IMRT). Five 5% of the 99 patients who underwent ENPG and 20 20% of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity.
Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy.
Sun Yat-sen University Clinical Research 5010 Program
The design of square‐planar Pt(II) complexes with highly efficient solid‐state near infrared (NIR) luminescence for electroluminescence is attractive but challenging. This study presents the ...fine‐turning of excited‐state properties and application of a series of isoquinolinyl pyrazolate Pt(II) complexes that are modulated by steric demanding substituents. It reveals that the bulky substituents do not always disfavor metallophilic Pt···Pt interactions. Instead, π–π stacking among chelates, which are fine‐tuned by the associated substituents, also exerts strong influence to the metal‐metal‐to‐ligand charge transfer (MMLCT) transition character. Theoretical calculations indicate that Pt···Pt contacts become more relevant in the trimers rather than the dimers, especially in their T1 states, associated with a change from mixed 3LC/3MLCT transition in the monomer/dimer to mixed 3LC/3MMLCT transition character in the trimer. Electroluminescence devices affording intense deep‐red/NIR emission (near 670 nm) with unprecedentedly high external quantum efficiency over 30% are demonstrated. This work provides deep insights into formation MMLCT transition of square‐planar Pt(II) complexes and efficient molecular design for deep‐red/NIR electroluminescence.
A series of deep‐red/near infrared phosphorescent square‐planar isoquinolinyl pyrazolate Pt(II) complexes modeled by sterically demanding substituents is designed and demonstrates high photoluminescence quantum efficiencies and short excited‐state lifetimes. This allows highly efficient deep‐red/near infrared organic electroluminescence with an external quantum efficiency as high as 30% and peak wavelength of ≈670 nm.
Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. ...However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Stem Cells 2017;35:2138-2149.
Research into organic light emitters employing multiple resonance-induced thermally activated delayed fluorescence (MR-TADF) materials is presently attracting a great deal of attention due to the ...potential for efficient deep-blue emission. However, the origins and mechanisms of successful TADF are unclear, as many MR-TADF materials do not show TADF behaviour in solution, but only as particular pure solids. Here, an investigation into a well-known MR-TADF material, DABNA-1, together with other new MR materials (9H-quinolino3,2,1-klphenothiazin-9-one (QPO) and 9H-quinolino-3,2,1-kl-phenothiazin-9-one 5,5-dioxide (QP3O)), yields new insights regarding the origin of TADF. Although a material system may support the concept of MR, inefficiency in both forward and reverse intersystem crossings forbids TADF unless a suitable host material allows an exciplex-like host–emitter interaction that boosts TADF. This boosted-TADF mechanism can be generalized to any fluorescence dye that lacks TADF in the photoluminescence measurement but has a thermally accessible S1–T1 energy gap, opening the way to high-performance organic light-emitting diodes.This study reveals the importance of host–guest interactions for effective multiple-resonance thermally activated delayed fluorescence in organic light emitters.
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.
Abstract
Background
Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of over 98% of the US population. Studies among highly exposed ...individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population.
Methods
We measured prediagnostic serum concentrations of PFOA and 7 additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were 2-sided.
Results
We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37, P = .002) and a greater than twofold increased risk among those in the highest quartile vs the lowest (OR = 2.63, 95% CI = 1.33 to 5.20, Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63, P = .02) and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed 8 or more years after phlebotomy.
Conclusions
Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical.
Inflammatory pain sensation is an important symptom which protects the body against additional tissue damage and promotes healing. Discovering long-term and effective treatments for pain remains ...crucial in providing efficient healthcare. Electroacupuncture (EA) is a successful therapy used for pain relief. We aimed to investigate effects and mechanisms of Complete Freund's Adjuvant (CFA)-inducing inflammatory pain in the cerebellum, and the inhibition of this inflammatory hyperalgesia using EA at Zusanli acupoint (ST36). The results display a significant increase in mechanical and thermal sensitivities in the CFA and CFA + SHAM groups, which was significantly reduced in the CFA+EA and CFA + KO groups. This evidence was substantiated in the protein levels observed using immunoblotting, and presented with significant escalations after CFA inducing inflammatory hyperalgesia in CFA and CFA + SHAM groups. Then, they were significantly attenuated by EA in the CFA + EA group. Furthermore, the CFA + transient receptor vanilloid member 1 (TRPV1)
group indicated similar significant decreases of protein expression. Additionally, a concomitant overexpression in lobule VIa was also observed in immunofluorescence. These consequences suggest that CFA-induced inflammatory pain provokes modifications in cerebellum lobules V, VIa and VII, which can subsequently be regulated by EA treatment at the ST36 through its action on TRPV1 and related molecular pathways.
PDF
