Sulfone-Embedded Heterocyclic Narrowband Emitters with Strengthened Molecular Rigidity and Suppressed High-Frequency Vibronic Coupling.

Sulfone-embedded heterocyclics are of great interest in organic light-emitting diodes (OLEDs), however, exploring highly efficient narrowband emitters based on sulfone-embedded heterocyclics remains challenging. Herein, five emitters with different sulfur valence state and molecular rigidity, namely tP, tCPD, 2tCPD, tPD and tPT, are thoroughly analysed. With restricted twisting of flexible peripheral phenyl by strengthening molecular rigidity, molecular emission spectra can be enormously narrowed. Further, introducing the sulfone group with bending vibration in low-frequency region that suppresses high-frequency vibration, sharp narrow full-widths at half-maximum of 28 and 25 nm are achieved for 2tCPD and tPD, respectively. Maximum external quantum efficiencies of 22.0 % and 27.1 % are successfully realized for 2tCPD- and tPD-based OLED devices. These results offer a novel design strategy for constructing narrowband emitters by introducing sulfone group into a rigid molecular framework.

Novel Polycyclic Fused Amide Derivatives: Properties and Applications for Sky-blue Electroluminescent Devices.

Aromatic imide derivatives play a critical role in boosting the electroluminescent (EL) performance of organic light-emitting diodes (OLEDs). However, the majority of aromatic imide-based materials are limited to long wavelength emission OLEDs rather than blue emissions due to their strong electron-withdrawing characteristics. Herein, two novel polycyclic fused amide units were reported as electron acceptor to be combined with either a tetramethylcarbazole or acridine donor via a phenyl linker to generate four conventional fluorescence blue emitters of BBI-4MeCz, BBI-DMAC, BSQ-4MeCz and BSQ-DMAC for the first time. BSQ-4MeCz and BSQ-DMAC based on a BSQ unit exhibited higher thermal stability and photoluminescence quantum yields than BBI-4MeCz and BBI-DMAC based on a BBI unit due to their more planar acceptor structure. The intermolecular interactions that exist in the BSQ series materials effectively inhibit the molecular rotation and configuration relaxation, and thus allow for blue-shifted emissions. Blue OLED devices were constructed with the developed materials as emitters, and the effects of both the structure of the polycyclic fused amide acceptor and the electron donor on the EL performance were clarified. Consequently, a sky-blue OLED device based on BSQ-DMAC was created, with a high maximum external quantum efficiency of 4.94% and a maximum luminance of 7761 cd m-2.

Hydrogen-Transfer-Mediated N-Arylation of Naphthols Using Indolines as Hydrogen Donors.

Using a hydrogen-transfer-mediated activation mode, we report a new catalytic system for the transfer hydrogenation of naphthols. In the presence of the Pd/C catalyst and base, various naphthols reacted with indolines to afford N-aryl-substituted heterocyclic compounds. Indolines were found to act as novel hydrogen donors for naphthols under palladium catalysis. This method features good functional tolerance, operational simplicity, and a readily available catalyst.

The Impact of Trainee Nationality on Patient Acceptance of Obstetrics and Gynecology Care: A Chinese Study.

Phenomenon: China is a relatively homogenous nation where the majority of people are Han Chinese. In recent years, a large number of international students have begun to study medicine in China. Due to the privacy and intimacy associated with obstetrical and gynecological diseases, Chinese women's acceptance toward international students' involvement in their care has not been reported thus far. This survey aims (1) to determine Chinese women's attitudes toward both Chinese and international medical student involvements in obstetrical and gynecological outpatient departments and (2) to investigate possible reasons, if any, for their rejection of the medical students. Approach: We conducted a cross-sectional survey study using a locally-developed questionnaire. The survey was conducted in the obstetrical and gynecological outpatient department of a tertiary hospital in a Chinese harbor city. We surveyed 600 patients for their attitudes towards the involvement of four groups of medical student in clinical practice: Chinese female, International female, Chinese male, and International male. Among the returned questionnaires, 501 satisfied the criteria for analysis. Findings: Patient's acceptance rates of the four groups of students (Chinese female, International female, Chinese male, and International male) were 59.7%, 55.9%, 32.1%, and 25.9%, respectively. Analysis revealed that language barriers and lack of friendliness were the two main reasons leading to patients' low acceptance rates of international students. Insights: Obstetrical and gynecological patients are more likely to accept female students over male students, regardless of their nationality, however International male students receive the least acceptance. For international students, improving their Chinese language skills and using more friendly expressions may facilitate their practice in China.

Transition metal-free α-methylation of 1,8-naphthyridine derivatives using DMSO as methylation reagent.

A practical approach to the direct α-methylation of 1,8-naphthyridines under mild reaction conditions has been developed using simple and readily available DMSO as a convenient and environmentally friendly carbon source. This method is transition metal-free and highly chemoselective, shows good functional group tolerance, and uses DMSO as a methyl source, providing efficient and rapid access to an important compound class, 2-methyl-1,8-naphthyridines.

[Quantitative Segmentation and Measurement of Tooth from Computed Tomography Image Based on Regional Adaptive Deformation Model].

For tooth segmentation problem on the three-dimensional computed tomography(CT)volume data,this paper proposes a regional adaptive deformable model for tooth structure measurement of CT images.The proposed method combines the automatic thresholding segmentation,CV active contour model,and graph-cut.Firstly,we achieved the segmentation and location of dental crowns by automatic thresholding segmentation.And then by using the above segmentation result as the initial contour,we utilized active contour method to slice gradually the segment of remaining tooth.By incorporating active contour and graph-cut then,we realized the accurate segmentation for tooth root,which is the most difficult to be segmented.The experimental results showed that the proposed tooth structure measurement accurately and automatically segmented dental crowns from CT data,and then rapidly and accurately segmented the tooth neck and tooth root.The structure of tooth could be effectively segmented from CT data by using the proposed method.Experimental results indicated that the proposed method was rather robust and accurate,and could effectively assist the doctor for diagnosis in clinical treatment.

Highly Horizontal Oriented Tricomponent Exciplex Host with Multiple Reverse Intersystem Crossing Channels for High-Performance Narrowband Electroluminescence and Eye-Protection White Organic Light-Emitting Diodes.

Despite multiple-resonance thermally activated delayed fluorescence (MR-TADF) emitters with small full-width at half maximum are attractive for wide color-gamut display and eye-protection lighting applications, their inefficient reverse intersystem crossing (RISC) process and long exciton lifetime induce serious efficiency roll-off, which significantly limits their development. Herein, a novel device concept of building highly efficient tricomponent exciplex with multiple RISC channels is proposed to realize reduced exciton quenching and enhanced upconversion of nonradiative triplet excitons, and subsequently used as a host for high-performance MR-TADF organic light-emitting diodes (OLEDs). Compared with traditional binary exciplex, the tricomponent exciplex exhibits obviously improved photoluminescence quantum yield, emitting dipole orientation and RISC rate constant, and a record-breaking external quantum efficiency (EQE) of 30.4% is achieved for tricomponent exciplex p-PhBCzPh: PO-T2T: DspiroAc-TRZ (50: 20: 30) based OLED. Remarkably, maximum EQEs of 36.2% and 40.3% and ultralow efficiency roll-off with EQEs of 26.1% and 30.0% at 1000 cd m-2 are respectively achieved for its sky-blue and pure-green MR-TADF doped OLEDs. Additionally, the blue emission unit hosted by tricomponent exciplex is combined with an orange-red TADF emission unit to achieve a double-emission-layer blue-hazard-free warm white OLED with an EQEmax of 30.3% and stable electroluminescence spectra over a wide brightness range.

Mirk/Dyrk1B mediates G0/G1 to S phase cell cycle progression and cell survival involving MAPK/ERK signaling in human cancer cells.

BACKGROUND: Mirk/Dyrk1B contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1 to maintain the viability of quiescent human cancer cells, and it could be negatively regulated by mitogenic-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling. This study was performed to investigate the effect of Mirk/Dyrk1B on cell cycle and survival of human cancer cells involving MAPK/ERK signaling. METHODS: The correlations between Mirk/Dyrk1B expression and active ERK1/2 detected by western blot in both ovarian cancer and non-small cell lung cancer (NSCLC) cells were analyzed by simple regression. Mirk/Dyrk1B unique phosphopeptides with sites associated with Mirk/Dyrk1B protein were isolated and quantitated by liquid chromatography coupled to tandem mass/mass spectrometry (LC-MS/MS) proteomics analysis. The human cancer cells were treated with small interfering RNAs (siRNAs) and/or U0126, an inhibitor of MEK for indicated duration, followed by investigating the alterations of cell cycle and apoptosis as well as related proteins examined by flow cytometry and Western blot, respectively. RESULTS: Our study demonstrated the widely expressed Mirk/Dyrk1B proteins in the human cancer cells were positively correlated with the levels of activated ERK1/2. Moreover, Mirk/Dyrk1B protein expressions consistent with the tyrosine autophosphorylated levels in the human cancer cells were increased by U0126 or growth factor-depleted culture. Conversely, knockdown of Mirk/Dyrk1B by siRNA led to up-regulated activation of c-Raf-MEK-ERK1/2 pathway and subsequent changes in cell cycle proteins (cyclin D1, p27kip1), accompanied by increased growth rate and cells from G0/G1 into S of cell cycle which could be blocked by U0126 in a dose-dependent manner, indicating Mirk/Dyrk1B may sequester MAPK/ERK pathway, and vice versa. Whereas, combined Mirk siRNA and U0126 induced cell apoptosis in the human cancer cells. CONCLUSIONS: These data together show that Mirk/Dyrk1B mediates cell cycle and survival via interacting with MAPK/ERK signals and simultaneous inhibition of both pathways may be a novel therapeutic target for human cancer.

Effect of finerenone on cardiovascular events in kidney disease and/or diabetes: a meta analysis of randomized control trials.

OBJECTIVE: To evaluate the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes. METHODS: The ClinicalTrials.gov, Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to December 20, 2021 in order to identify randomized controlled trials that evaluated the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes, without language restriction. This meta-analysis collected data from 7 randomized clinical trials that evaluated the effect of finrrenone in 15,618 patients with kidney disease and/or diabetes. Risk of bias was assessed by Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed by I2 statistic. The main endpoints included death from cardiovascular causes, death from any cause, incidence of myocardial infarction, rate of heart failure, hospitalization for any cause, rate of total advent events and study-drug-related adverse events. RESULTS: A total of 7 randomized controlled trials involving 15,618 fulfilled the inclusion criteria. The outcomes of this meta-analysis presented that finerenone significantly reduced the death from any cause (95% CI 0.82-0.99; P = 0.031), risk of heart failure (95% CI 0.67-0.92; P = 0.002) among patients with kidney disease and/or diabetes when compared to control group. Besides, finerenone could not reduce the incidence of death from cardiovascular, myocardial infarction and hospitalization for any cause among patients with kidney disease and/or diabetes (p > 0.05). In terms of safety, finerenone shared the same risk of total advent events with placebo among patients with kidney disease and/or diabetes (p > 0.05). However, finerenone had higher risk of study-drug-related advent events than placebo among patients with kidney disease and/or diabetes (95% CI 1.27-1.48; P < 0.001). CONCLUSIONS: In patients with kidney disease and/or diabetes, treatment with finerenone resulted in lower risk of death from any cause and heart failure than placebo. However, the study-drug-related advent events also increased significantly at the same time.

Protective Effects of Shen-Yuan-Dan Capsule against Ischemia/Reperfusion Injury in Cardiomyocytes by Alleviating Endoplasmic Reticulum Stress.

Objective: Endoplasmic reticulum (ER) stress leads to the accumulation of misfolded proteins and an active unfolded protein response (UPR). If the ER stress is not resolved, the UPR triggers activation of the apoptotic cell death program. It has been shown that ischemia/reperfusion (I/R) injury can induce apoptosis via the ER stress pathway. We previously found that Shen-Yuan-Dan capsule (SYDC), a widely used traditional Chinese medicine, reduces I/R injury. Here, we investigated whether SYDC protects against cardiomyocyte apoptosis by reducing ER stress during I/R injury and. if so, explored its mechanism of action. Methods: We use forty male Wistar rats to prepare the SYDC pharmacological serum. An I/R injury model was established using cultures of neonatal rat ventricular myocytes where cells were exposed to 2 h of reduced oxygenation followed by 4 h of normal oxygenation. After treatment of cultured cells with serum containing SYDC for 4 h, reverse transcription polymerase chain reaction and western blotting were performed to assess the expression levels of target molecules. Results: Ischemia/reperfusion (I/R) clearly decreased cell viability. Treatment of cells with SYDC in serum (5% and 10%) increased cell viability compared with control serum-treated I/R cardiomyocytes. The mRNA levels of glucose-regulated protein 78 (Grp78), C/EBP homologous protein (CHOP), and caspase-12 were significantly upregulated in the I/R group. The mRNA levels of Grp78, CHOP, and caspase-12 were significantly decreased in the 5% and 10% SYDC groups compared to the I/R group. The protein expression levels of Grp78, CHOP, and caspase-12 were significantly upregulated in the I/R group. Treatment of I/R cardiomyocytes with 5% or 10% SYDC reduced the expression levels of CHOP and caspase-12, while the control serum did not show this effect. Conclusions: These findings demonstrate that SYDC alleviates ER stress and prevents ER stress-induced apoptosis via the CHOP-dependent pathway.

Reliability Analysis of Critical Systems in A Fuel Booster Pump Using Advanced Simulation Techniques.

The fuel booster pump is one of the most vulnerable physical assets in an operating engine due to the harsh environmental and operational conditions. However, because of its high structural complexity and extreme operational conditions, the reliability design of the fuel booster pump becomes especially difficult, particularly by means of experiments. Thus, to overcome such a problem, advanced simulation techniques have become adequate solutions for the reliability assessment and analysis of a fuel booster pump at the design stage. In this paper, by considering the effects of the uncertainties of multiple design parameters, fatigue life distributions of the four key components (which are the sealing bolt, spline shaft, graphite ring, and inducer, respectively) in a fuel booster pump were first predicted by PoF-based reliability simulations. Then, through further sensitivity analysis on each key component, the design parameters most sensitive to the component mean fatigue life were detected from a total of 25 candidate parameters. These parameters include the "nominal diameter" and "preload" for the sealing bolt, "major and minor diameters of the small spline" for the spline shaft, "inside diameter" for the graphite ring, and "fuel pressure on the blade front surface" for the inducer, respectively. These sensitivity results were found to be in good agreement with the results from the qualitative cause analysis on each key component.

Effect of Annealing Temperature on the Microstructure and Mechanical Properties of High-Pressure Torsion-Produced 316LN Stainless Steel.

316LN stainless steel is a prospective structural material for the nuclear and medical instruments industries. Severe plastic deformation (SPD) combined with annealing possesses have been used to create materials with excellent mechanical properties. In the present work, a series of ultrafine-grained (UFG) 316LN steels were produced by high-pressure torsion (HPT) and a subsequent annealing process. The effects of annealing temperature on grain recrystallization and precipitation were investigated. Recrystallized UFG 316LN steels can be achieved after annealing at high temperature. The σ phase generates, at grain boundaries, at an annealing temperature range of 750-850 °C. The dislocations induced by recrystallized grain boundaries and strain-induced nanotwins are beneficial for enhancing ductility. Moreover, microcracks are easy to nucleate at the σ phase and the γ-austenite interface, causing unexpected rapid fractures.

Balanced crystalloids versus saline in critically ill patients: The PRISMA study of a meta-analysis.

OBJECTIVE: To compare the safety of balanced crystalloids and saline among critically ill patients in intensive care unit (ICU). METHODS: The Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to May 17, 2020 in order to identify randomized controlled trials which evaluated the safety of balanced crystalloids and saline in critically ill patients. The primary outcome was major adverse kidney events within 30 days (MAKE30). The second outcomes included 30-day mortality, ICU mortality, In-hospital mortality, ICU length of stay, hospital length of stay, creatinine highest before discharge (mg/dl) and needs for renal replacement therapy (RRT). RESULTS: A total of nine randomized controlled trials involving 19,578 critical ill patients fulfilled the inclusion criteria. The outcomes of this meta-analysis showed that balanced crystalloids treatment shared the same risk of MAKE30 with saline treatment among critical ill patients [RR = 0.95; 95%CI, 0.88 to 1.01; Z = 1.64 (P = .102)]. The clinical mortality which included 30-day mortality [RR = 0.92; 95%CI, 0.85 to 1.01; Z = 1.78 (P = .075)], ICU mortality [RR = 0.92; 95%CI, 0.83 to 1.02; Z = 1.67 (P = .094)] and In-hospital mortality [RR = 0.93; 95%CI, 0.71 to 1.21; Z = 0.55 (P = .585)] were similar between balanced crystalloids treatment and saline treatment among critical ill patients. Patients who received balanced crystalloids treatment or saline treatment needed the same length of ICU stay [WMD = 0.00; 95%CI, -0.09 to 0.10; Z = 0.09 (P = .932)] and hospital stay [WMD = 0.59; 95%CI, -0.33 to 1.51; Z = 1.26 (P = .209)]. Critical ill patients who received balanced crystalloids treatment or saline treatment had the same level of creatinine highest before discharge [WMD = 0.01; 95%CI, -0.02 to 0.04; Z = 0.76 (P = .446)] and needs for RRT [RR = 1.04; 95%CI, 0.75 to 1.43; Z = 0.21 (P = .830)]. Similar results were obtained in subgroups of trials stratified according to the age of patients (children or adults). CONCLUSIONS: When compared with saline, balanced crystalloids could not reduce the risk of MAKE30, 30-day mortality, ICU mortality and in-hospital mortality, could not reduce the length of ICU stay, length of hospital stay, the level of creatinine highest before discharge and the needs for RRT among critical ill children and adults. Therefore, it was still too early for balanced crystalloids to replace normal saline among critical ill patients.

Mono/Dual Amination of Phenols with Amines in Water.

We herein describe a practical direct amination of phenols through a palladium-catalyzed hydrogen-transfer-mediated activation method to synthesize the secondary and tertiary amines. In this conversion, environmentally friendly water and inexpensive ammonium formate were used as solvent and reductant, respectively. A range of amines, including aliphatic amines, aniline, secondary amines, and diamines, could be coupled effectively by this method to achieve mono/dual amination and cyclization of phenols. This study not only provides a green and mild strategy for the synthesis of secondary and tertiary naphthylamines but also expands the synthesis of chloroquine in organic chemistry.

Association between anti-TNF therapy for rheumatoid arthritis and hypertension: a meta-analysis of randomized controlled trials.

Tumor necrosis factor (TNF) is an important and pleiotropic cytokine which is also involved in the pathogenesis of inflammation in rheumatoid arthritis (RA), and RA treated with anti-TNF agents with a subsequent increase in hypertension risk is also observed in clinical trials. However, it is confusing that to what extent treatment with anti-TNF agents for RA might be associated with increasing risk of hypertension. The aim of this study was to investigate the overall incidence and risk of hypertension in RA patients who receive anti-TNF agents. The databases of Embase, PubMed, the Cochrane Library, and clinical trial registration Web site were searched for relevant trials. Statistical analyses were conducted to calculate the overall incidence, odds ratios, and 95% confidence intervals (CI) by using either random-effects or fixed-effect models according to the heterogeneity of the included studies. A total of 6321 subjects with RA from 11 randomized clinical trials (RCTs) were included in the meta-analysis. The overall incidence of hypertension associated with anti-TNF agent was 3.25% (95% CI: 1.51%-6.89%). The use of anti-TNF agent significantly increased the risk of developing hypertension (OR = 1.8896, 95% CI: 1.35-2.65). Sensitivity analysis showed that the OR between anti-TNF therapy and controls is not significantly influenced by omitting any single study. No evidence of publication bias was observed. Anti-TNF therapy is associated with a significantly increased risk of developing hypertension in patients with RA. Physicians should be aware of this risk and provide continuing monitoring in patients receiving these therapies.

Interleukin 1 inhibition with anakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety.

BACKGROUND: Anakinra is the first interleukin-1 inhibitor to be used in clinical practice, and recent evidence showed that interleukin-1 plays a pivotal role in the pathogenesis of adult-onset Still disease (AoSD). However, data concerning efficacy with anakinra use in different clinical trials has not been evaluated, and the overall remission of AoSD with anakinra treatment has not been well defined. METHODS: We conducted a search on Embase, PubMed, and the Cochrane Library for relevant trials. Statistical analyses were conducted to calculate the overall remission rates, odds ratios (OR), and 95% confidence intervals (CI), by using either random effects or fixed effect models according to the heterogeneity. RESULTS: Of the 273 articles that were identified, 265 were excluded. Eight studies were eligible for inclusion. The overall remission rate and complete remission rate of anakinra in AoSD patients were 81.66% (95% CI: 69.51%-89.69%) and 66.75% (95% CI: 59.94%-75.3%), respectively. Compared with the controls, the use of anakinra was associated with a significant remission in AoSD, with an OR of 0.16 (95% CI: 0.06-0.44, P=0.0005). There were also significant reductions of the dosage of corticosteroid (mean difference =21.19) (95% CI: 13.2-29.18, P<0.0001) from anakinra onset to the latest follow up time. Clinical and laboratory parameters were all improved, and anakinra was well tolerated in patients with AoSD. No evidence of publication bias was observed. CONCLUSION: Our study has shown that anakinra is effective in remitting the manifestations of AoSD, with reduction of the dose of corticosteroid in patients with AoSD. Further, anakinra therapy was not associated with increased risk of adverse events, and it was well tolerated in patients with AoSD. Further research is still recommended to investigate these findings.

c-Jun transcriptionally regulates alpha 1, 2-fucosyltransferase 1 (FUT1) in ovarian cancer.

Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown. Here, we identify an AP-1 binding site in FUT1 promoter in ovarian cancer cells. c-Jun promotes FUT1 expression, thereby enhancing Lewis y biosynthesis in various ovarian cancer cell lines. Moreover, EMSA, luciferase activity and ChIP assays demonstrate c-Jun directly interacts with FUT1 promoter. Furthermore, FUT1 mediates c-Jun-induced cell proliferation in ovarian cancer cells. In human ovarian cancer samples, c-Jun overexpression is linked to malignant degree and positively correlated to FUT1 and Lewis y expression. Taken together, c-Jun could transcriptionally modulate FUT1 expression in ovarian cancer, implicating the potential application of c-Jun inhibitors for human ovarian cancer therapy.