Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high‐efficient red organic light‐emitting diodes (OLEDs) and non‐doped deep red/near‐infrared (NIR) OLEDs, ...is challenging. Now, two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non‐doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π–π interactions. mDPBPZ‐PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ‐PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non‐doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680 nm.
Two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED.
Background and Purpose
Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents ...cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose‐induced hypertension.
Experimental Approach
Rats were fed 10% fructose with or without resveratrol (10 mg·kg−1·day−1) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail‐cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real‐time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels.
Key Results
In fructose‐fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22‐phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP‐activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose‐fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose‐fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose‐fed rats.
Conclusions and Implications
Collectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose‐fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.
Developing low‐cost and high‐activity pH‐universal hydrogen evolution reaction (HER) catalysts is very crucial to the industrialization of water electrolysis. However, the high price, low yield, and ...poor stability of current HER catalysts make them difficult to meet practical requirements. Herein, a plasma spraying technique is employed to prepare self‐supported Cu catalysts with tensile strain for the first time. The tensile strain upshifts the d‐band of Cu, improves the water dissociation and H* adsorption, eventually improves the intrinsic HER catalytic activity. As such, Cu electrode achieves overpotentials of 182 mV in 0.5 m H2SO4, 261 mV in 1 M PBS, and 121 mV in 1 M KOH at 10 mA cm–2. In addition, Cu electrode also performs well at high current densities, the overpotentials at 1 A cm–2 are much lower than those of Pt foil in acid, neutral, and alkaline solutions.
The Cu electrode prepared by plasma spraying exhibits an excellent pH‐universal HER catalytic activity, superb long‐term stability, and marvelous corrosion resistance. The superb HER activity is attributed to self‐supported porous structure, abundant active sites, tensile strain enhanced intrinsic catalytic activity, and small charge transfer resistance.
Aims/Introduction
Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening ...cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics.
Materials and Methods
Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency LF, high frequency HF, and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score.
Results
The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P < 0.0001). Multiple linear regression analysis also showed that feet ESC and SDNN value (P = 0.003 and P < 0.0001) were significantly associated with CAN score. Combining SDNN and feet ESC also can increase the diagnostic accuracy of CAN with respective to sensitivity and specificity by using receiver operating characteristic analysis.
Conclusions
Combining the results of SDNN and feet ESC can not only assess, but also quantitatively reflect the progress or improvement of autonomic nerve function (including sympathetic and parasympathetic activity) in patients with T2DM.
Whether goal-directed fluid therapy based on dynamic predictors of fluid responsiveness (GDFTdyn) alone improves clinical outcomes in comparison with standard fluid therapy among patients undergoing ...surgery remains unclear.
PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched for relevant studies. Studies comparing the effects of GDFTdyn with that of standard fluid therapy on clinical outcomes among adult patients undergoing surgery were considered eligible. Two analyses were performed separately: GDFTdyn alone versus standard fluid therapy and GDFTdyn with other optimization goals versus standard fluid therapy. The primary outcomes were short-term mortality and overall morbidity, while the secondary outcomes were serum lactate concentration, organ-specific morbidity, and length of stay in the intensive care unit (ICU) and in hospital.
We included 37 studies with 2910 patients. Although GDFTdyn alone lowered serum lactate concentration (mean difference (MD) - 0.21 mmol/L, 95% confidence interval (CI) (- 0.39, - 0.03), P = 0.02), no significant difference was found between groups in short-term mortality (odds ratio (OR) 0.85, 95% CI (0.32, 2.24), P = 0.74), overall morbidity (OR 1.03, 95% CI (0.31, 3.37), P = 0.97), organ-specific morbidity, or length of stay in the ICU and in hospital. Analysis of trials involving the combination of GDFTdyn and other optimization goals (mainly cardiac output (CO) or cardiac index (CIx)) showed a significant reduction in short-term mortality (OR 0.45, 95% CI (0.24, 0.85), P = 0.01), overall morbidity (OR 0.41, 95% CI (0.28, 0.58), P < 0.00001), serum lactate concentration (MD - 0.60 mmol/L, 95% CI (- 1.04, - 0.15), P = 0.009), cardiopulmonary complications (cardiac arrhythmia (OR 0.58, 95% CI (0.37, 0.92), P = 0.02), myocardial infarction (OR 0.35, 95% CI (0.16, 0.76), P = 0.008), heart failure/cardiovascular dysfunction (OR 0.31, 95% CI (0.14, 0.67), P = 0.003), acute lung injury/acute respiratory distress syndrome (OR 0.13, 95% CI (0.02, 0.74), P = 0.02), pneumonia (OR 0.4, 95% CI (0.24, 0.65), P = 0.0002)), length of stay in the ICU (MD - 0.77 days, 95% CI (- 1.07, - 0.46), P < 0.00001) and in hospital (MD - 1.18 days, 95% CI (- 1.90, - 0.46), P = 0.001).
It was not the optimization of fluid responsiveness by GDFTdyn alone but rather the optimization of tissue and organ perfusion by GDFTdyn and other optimization goals that benefited patients undergoing surgery. Patients managed with the combination of GDFTdyn and CO/CI goals might derive most benefit.
Objective
Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional ...preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death‐preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes.
Methods
Associations of caregivers' death‐preparedness states (no‐death‐preparedness, cognitive‐death‐preparedness‐only, emotional‐death‐preparedness‐only, and sufficient‐death‐preparedness states) at last preloss assessment with bereavement outcomes over the first two bereavement years were evaluated among 332 caregivers of advanced cancer patients using hierarchical linear models with the logit‐transformed posterior probability for each death‐preparedness state.
Results
Caregivers with a higher logit‐transformed posterior probability for sufficient death‐preparedness state reported less prolonged‐grief symptoms, lower likelihoods of severe depressive symptoms and heightened decisional regret, and better mental health‐related quality of life (HRQOL). Caregivers with a higher logit‐transformed posterior probability for no‐death‐preparedness state reported less prolonged‐grief symptoms, a lower likelihood of severe depressive symptoms, and better mental HRQOL. A higher logit‐transformed posterior probability for cognitive‐death‐preparedness‐only state was associated with bereaved caregivers' higher likelihood of heightened decisional regret, whereas that for emotional‐death‐preparedness‐only state was not associated with caregivers' bereavement outcomes.
Conclusions
Caregivers' bereavement outcomes were associated with their preloss death‐preparedness states, except for physical health‐related QOL. Interventions focused on not only cultivating caregivers' accurate prognostic awareness but also adequately preparing them emotionally for their relative's forthcoming death are actionable opportunities for high‐quality end‐of‐life care and are urgently warranted to facilitate caregivers' bereavement adjustment.
Background/Objective
Facilitating death preparedness is important for improving cancer patients' quality of death and dying. We aimed to identify factors associated with the four death‐preparedness ...states (no‐preparedness, cognitive‐only, emotional‐only, and sufficient‐preparedness) focusing on modifiable factors.
Methods
In this cohort study, we identified factors associated with 314 Taiwanese cancer patients' death‐preparedness states from time‐invariant socio‐demographics and lagged time‐varying modifiable variables, including disease burden, physician prognostic disclosure, patient‐family communication on end‐of‐life (EOL) issues, and perceived social support using hierarchical generalized linear modeling.
Results
Patients who were male, older, without financial hardship to make ends meet, and suffered lower symptom distress were more likely to be in the emotional‐only and sufficient‐preparedness states than the no‐death‐preparedness‐state. Younger age (adjusted odds ratio 95% confidence interval = 0.95 0.91, 0.99 per year increase in age) and greater functional dependency (1.05 1.00, 1.11) were associated with being in the cognitive‐only state. Physician prognostic disclosure increased the likelihood of being in the cognitive‐only (51.51 14.01, 189.36) and sufficient‐preparedness (47.42 10.93, 205.79) states, whereas higher patient‐family communication on EOL issues reduced likelihood for the emotional‐only state (0.38 0.21, 0.69). Higher perceived social support reduced the likelihood of cognitive‐only (0.94 0.91, 0.98) but increased the chance of emotional‐only (1.09 1.05, 1.14) state membership.
Conclusions
Death‐preparedness states are associated with patients' socio‐demographics, disease burden, physician prognostic disclosure, patient‐family communication on EOL issues, and perceived social support. Providing accurate prognostic disclosure, adequately managing symptom distress, supporting those with higher functional dependence, promoting empathetic patient‐family communication on EOL issues, and enhancing perceived social support may facilitate death preparedness.
During rheumatoid arthritis (RA) treatment, long-term injection of antitumor necrosis factor α antibodies (anti-TNFα Abs) may induce on-target toxicities, including severe infections (tuberculosis TB ...or septic arthritis) and malignancy. Here, we used an immunoglobulin G1 (IgG1) hinge as an Ab lock to cover the TNFα-binding site of Infliximab by linking it with matrix metalloproteinase (MMP) -2/9 substrate to generate pro-Infliximab that can be specifically activated in the RA region to enhance the selectivity and safety of treatment. The Ab lock significantly inhibits the TNFα binding and reduces the anti-idiotypic (anti-Id) Ab binding to pro-Infliximab by 395-fold, 108-fold compared with Infliximab, respectively, and MMP-2/9 can completely restore the TNFα neutralizing ability of pro-Infliximab to block TNFα downstream signaling. Pro-Infliximab was only selectively activated in the disease site (mouse paws) and presented similar pharmacokinetics (PKs) and bio-distribution to Infliximab. Furthermore, pro-Infliximab not only provided equivalent therapeutic efficacy to Infliximab but also maintained mouse immunity against Listeria infection in the RA mouse model, leading to a significantly higher survival rate (71%) than that of the Infliximab treatment group (0%). The high-selectivity pro-Infliximab maintains host immunity and keeps the original therapeutic efficiency, providing a novel strategy for RA therapy.
Abstract
Background
The Wnt/β-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/β-catenin signaling pathway induces ...overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/β-catenin signaling pathway is important to understanding Wnt/β-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes.
Methods
Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo.
Results
The results showed that
RMI2
mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the β-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the
RMI2
promoter. We then found a TCF binding site at − 333/− 326 of the
RMI2
promoter, which is crucial for β-catenin responsiveness in liver cell lines.
RMI2
was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover,
RMI2
upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/β-catenin-related genes, but silencing
RMI2
had the opposite effects. Notably, the expression of
RMI2
was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both:
P
< 0.05). In addition, a total of 373 HCC patients’ data from the Caner Genome Atlas project (TCGA) were used to validate our findings.
Conclusions
Taking all these findings together, we determined that
RMI2
was a new target gene of the Wnt/β-catenin signaling pathway. We also found that
RMI2
promotes EMT markers, HCC cell invasion, and metastasis, which indicated that
RMI2
is a potential target for preventing or at least mitigating the progression of HCC.
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