Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial-mesenchymal transition.

PURPOSE: Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells. METHODS: Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial-mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2. RESULTS: Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells. CONCLUSION: Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Transfer-Imprinting-Assisted Growth of 2D/3D Perovskite Heterojunction for Efficient and Stable Flexible Inverted Perovskite Solar Cells.

2D/3D perovskite heterostructures show great potential to boost efficiency and stability of perovskite solar cells (PSCs). Here, a solvent-free transfer-imprinting-assisted growth (TIAG) method is employed to in situ grow 2D/3D perovskite heterojunctions. The solid-state transfer of spacer cation by the TIAG process enables a spatially confined growth of the 2D perovskite interlayer with uniform morphology between the 3D perovskites and charge transport layer. Meanwhile, the pressure associated with the TIAG process promotes the crystalline orientation, which is beneficial to carrier transport. As a result, the inverted PSC achieved a PCE of 23.09% (with certified 22.93%) and maintained 90% of their initial PCE after aging at 85 °C for 1200 h or operating for 1100 h under continuous AM 1.5 illumination. Flexible inverted PSCs achieved a PCE of 21.14% with mechanical robustness by maintaining above 80% of their initial PCE after 10000 bending cycles under a 3 mm bending radius.

Microfluidic rotating-target device capable of three-degrees-of-freedom motion for efficient in situ serial synchrotron crystallography.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

Triglyceride glucose index is associated with obstructive coronary artery disease in hypertensive patients.

BACKGROUND: Hypertension is a leading risk of coronary artery disease (CAD). Triglyceride glucose index (TyG) is a surrogate of insulin resistance (IR). Few studies explore the association between TyG and the incidence of obstructive CAD (OCAD) in hypertensive patients. METHODS: We retrospectively screened 1841 hypertensive subjects who were free of a history of CAD and underwent coronary computed tomography angiography (CCTA) because of chest pain. TyG index was calculated as ln (fasting TG [mg/dL] * fasting glucose [mg/dL]/2). The outcome of this research was OCAD, which was defined as the presence of diameter stenosis ≥ 50% in any of the four major epicardial coronary arteries detected on CCTA. RESULTS: A total of 310 (16.8%) patients developed obstructive CAD. The restricted cubic spline (RCS) analysis showed a J-shaped relationship between TyG and OCAD and the OR for OCAD increased as the TyG rose over 8.61 (OR perSD) 1.64, 95% CI 1.13-2.54, p = 0.008). After full adjustments for confounding covariates, patients with TyG index in tertile 3 (T3) had 2.12 times (95% CI 1.80 to 3.81) and in T2 had 2.01 times (95% CI 1.40 to 2.88) as high as the risk of OCAD compared with patients in T1 (p for trend = 0.001). When regarding TyG as a continuous variable, 1-SD increase elevated 49% (OR (95%CI), 1.49 (1.30-1.74)) risk of obstructive CAD (p = 0.007). This positive effect was still consistent across the subgroups (p for interaction > 0.05). CONCLUSION: TyG index was associated with the incidence of obstructive CAD in hypertensive patients.

Regulation of Tendon Stem Cell Behavior by Designed Nanoporous Topography of Microfibers.

Nano scale topography scaffold is more bioactive and biomimetic than smooth fiber topographies. Tendon stem cells (TSCs) play important roles in the tendinogenesis of tendon tissue engineering, but the effects and mechanisms of nano topography on TSC behavior are still unclear. This study determined whether the morphology, proliferation, cytoskeleton, and differentiation of TSCs are affected by topography of scaffold in vitro. The porous PA56 scaffolds were prepared with different concentration ratios of glycerol as the molecular template by electrospinning. Its topological characteristics, hydrophilicity, and degradation properties varied with glycerol proportion and movement rate of the receiving plate. Porous fibers promoted the proliferation of TSCs and the number of TSCs varied with topography. Although there was no significant difference due to the small sample size, the number of pseudopodia and cell polarizability still showed differences among different topographies. The morphology of actin cytoskeleton of TSCs showed difference among cultured on porous fibers, smooth fibers, and in culture media with no fiber, suggesting the orientation growth of cells on porous fiber. Moreover, porous fibers promoted teno-lineage differentiation of TSCs by upregulating tendon-specific gene expression. These findings provide evidence that nano porous topography scaffold promotes TSC proliferation, cytoskeleton orientation, and tenogenic differentiation.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Predictive value of machine learning algorithm of coronary artery calcium score and clinical factors for obstructive coronary artery disease in hypertensive patients.

BACKGROUND: The addition of coronary artery calcium score (CACS) to prediction models has been verified to improve performance. Machine learning (ML) algorithms become important medical tools in an era of precision medicine, However, combined utility by CACS and ML algorithms in hypertensive patients to forecast obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) is rare. METHODS: This retrospective study was composed of 1,273 individuals with hypertension and without a history of CAD, who underwent dual-source computed tomography evaluation. We applied five ML algorithms, coupled with clinical factors, imaging parameters, and CACS to construct predictive models. Moreover, 80% individuals were randomly taken as a training set on which 5-fold cross-validation was done and the remaining 20% were regarded as a validation set. RESULTS: 16.7% (212 out of 1,273) of hypertensive patients had obstructive CAD. Extreme Gradient Boosting (XGBoost) posted the biggest area under the receiver operator characteristic curve (AUC) of 0.83 in five ML algorithms. Continuous net reclassification improvement (NRI) was 0.55 (95% CI (0.39-0.71), p < 0.001), and integrated discrimination improvement (IDI) was 0.04 (95% CI (0.01-0. 07), p = 0.0048) when the XGBoost model was compared with traditional Models. In the subgroup analysis stratified by hypertension levels, XGBoost still had excellent performance. CONCLUSION: The ML model incorporating clinical features and CACS may accurately forecast the presence of obstructive CAD on CCTA among hypertensive patients. XGBoost is superior to other ML algorithms.

Feno differentiates epithelial gene expression clusters: Exploratory analysis from the MESOS randomized controlled trial.

BACKGROUND: Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis. OBJECTIVE: This post hoc exploratory analysis of the phase II tralokinumab trial MESOS (ClinicalTrials.gov identifier NCT02449473) aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma. METHODS: The T2 and T17 gene expression signatures, 3-gene mean and 5-gene mean, were calculated through transcriptomic analysis of baseline bronchial brushing samples. Clustering analysis using these signatures identified 3 distinct inflammatory subgroups: T2LOW/T17HIGH (n = 33), T2HIGH/T17LOW (n = 10), and T2LOW/T17LOW (n = 27). RESULTS: Fractional exhaled nitric oxide (Feno) levels were highest for T2HIGH/T17LOW and lowest for T2LOW/T17HIGH (median = 52.0 [range 42.5-116.3] and median = 18.8 [range 6.6-128.6] ppb, respectively; P = .003). High Feno levels were strongly correlated with high T2 gene expression (Spearman ρ = 0.5537; P < .001). Individual genes differentially expressed in patients with elevated levels of Feno, blood and bronchial submucosal eosinophil counts, and IgE level were explored, with cystatin SN (CST1) being the most upregulated gene in all subgroups (4.49- to 34.42-fold upregulation across clinically defined subgroups with high biomarker expression). CONCLUSION: Feno level may be useful to differentiate patients with T2 or T17 gene expression. Elevated Feno levels are associated with high CST1 expression.

Efficient and stretchable organic light-emitting devices based on spontaneously formed disordered wrinkles.

We propose a facile, scalable strategy to introduce spontaneously formed disordered wrinkles into organic light-emitting devices (OLEDs) to enhance light extraction and realize stretchability of the devices. The luminance and current efficiency of the wrinkled OLEDs are improved by 37% and 18%, respectively, compared to the planar device. Meanwhile, broadband light scattering induced by the disordered wrinkles results in angle-stable electroluminescent spectra at wide viewing angles for the wrinkled OLEDs. The disordered wrinkles enable the OLEDs to be stretchable and withstand hundreds of stretching-releasing cycles at strain between 0% and 5%. This study provides a simple method to realize stretchable OLEDs with high efficiency.

Predictive value of CAC score combined with clinical features for obstructive coronary heart disease on coronary computed tomography angiography: a machine learning method.

OBJECTIVE: We investigated the predictive value of clinical factors combined with coronary artery calcium (CAC) score based on a machine learning method for obstructive coronary heart disease (CAD) on coronary computed tomography angiography (CCTA) in individuals with atypical chest pain. METHODS: The study included data from 1,906 individuals undergoing CCTA and CAC scanning because of atypical chest pain and without evidence for the previous CAD. A total of 63 variables including traditional cardiovascular risk factors, CAC score, laboratory results, and imaging parameters were used to build the Random forests (RF) model. Among all the participants, 70% were randomly selected to train the models on which fivefold cross-validation was done and the remaining 30% were regarded as a validation set. The prediction performance of the RF model was compared with two traditional logistic regression (LR) models. RESULTS: The incidence of obstructive CAD was 16.4%. The area under the receiver operator characteristic (ROC) for obstructive CAD of the RF model was 0.841 (95% CI 0.820-0.860), the CACS model was 0.746 (95% CI 0.722-0.769), and the clinical model was 0.810 (95% CI 0.788-0.831). The RF model was significantly superior to the other two models (p < 0.05). Furthermore, the calibration curve and Hosmer-Lemeshow test showed that the RF model had good classification performance (p = 0.556). CAC score, age, glucose, homocysteine, and neutrophil were the top five important variables in the RF model. CONCLUSION: RF model was superior to the traditional models in the prediction of obstructive CAD. In clinical practice, the RF model may improve risk stratification and optimize individual management.

Simultaneous determination of 31 endocrine disrupting chemicals in fish plasma by solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry.

Solid phase extraction combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 31 endocrine-disrupting chemicals in fish plasma. The strong anion exchange/primary-secondary amine cartridge and the mixed cation exchange cartridge were used in tandem instead of using a single mixed cation exchange cartridge for sample purification. Suitable eluents were selected for each of the two cartridges: 4.5% ammonia/acetonitrile solution for cartridges in tandem and acetone:n-hexane (V:V = 3:7) for the strong anion exchange/primary-secondary amine cartridge alone. With this optimized Solid phase extraction method, the recoveries of 31 endocrine disrupting chemicals were between 43.0% and 131.3%, the method detection limits were 0.45 to 1.35 ng/ml, and the limits of quantitation were 1.50-4.50 ng/ml. The innovative pretreatment method that connects two cartridges in tandem is well positioned to mitigate the matrix effects of fish plasma, thereby improving the accuracy of multiclass endocrine-disrupting chemicals determination. The significance of this method is to facilitate the application of the fish plasma model for the environmental risk assessment of endocrine-disrupting chemicals.

Evolution of sex ratio through gene loss.

The maintenance of males at intermediate frequencies is an important evolutionary problem. Several species of Caenorhabditis nematodes have evolved a mating system in which selfing hermaphrodites and males coexist. While selfing produces XX hermaphrodites, cross-fertilization produces 50% XO male progeny. Thus, male mating success dictates the sex ratio. Here, we focus on the contribution of the male secreted short (mss) gene family to male mating success, sex ratio, and population growth. The mss family is essential for sperm competitiveness in gonochoristic species, but has been lost in parallel in androdioecious species. Using a transgene to restore mss function to the androdioecious Caenorhabditis briggsae, we examined how mating system and population subdivision influence the fitness of the mss+ genotype. Consistent with theoretical expectations, when mss+ and mss-null (i.e., wild type) genotypes compete, mss+ is positively selected in both mixed-mating and strictly outcrossing situations, though more strongly in the latter. Thus, while sexual mode alone affects the fitness of mss+, it is insufficient to explain its parallel loss. However, in genetically homogenous androdioecious populations, mss+ both increases male frequency and depresses population growth. We propose that the lack of inbreeding depression and the strong subdivision that characterize natural Caenorhabditis populations impose selection on sex ratio that makes loss of mss adaptive after self-fertility evolves.

miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.

Serum alkaline phosphatase levels are associated with coronary artery calcification patterns and plaque vulnerability.

OBJECTIVES: This study aimed to investigate the association of serum alkaline phosphatase (ALP) with calcification patterns and plaque morphology detected by intravascular ultrasound (IVUS) in acute coronary syndrome (ACS) patients. BACKGROUND: ALP has been shown to predict vascular calcification and long-term cardiovascular events. However, the relationship between ALP and vascular calcification patterns or plaque morphology remains unclear. METHODS: In total, 328 ACS patients who underwent IVUS examinations were screened from January 2017 to December 2018; among them, 234 eligible participants were grouped according to the tertiles of ALP levels (<68, 68-80, and >80 IU/L). Demographic data and IVUS parameters were documented and analyzed. RESULTS: After adjusting for potential confounders, independent associations were observed between ALP and the presence of coronary calcification, spotty calcification, minimum lumen area (MLA) ≤ 4.0 mm2 , and plaque burden (PB) > 70%. Compared with the lowest ALP tertile group, the highest ALP group had higher risks of calcification (odds ratio [OR], 2.85; 95% confidence interval [95%CI], 1.38-5.90; p = .005), spotty calcification (OR, 1.86; 95%CI, 1.09-3.84; p = .012), MLA≤4.0 mm2 (OR, 3.32; 95%CI, 1.51-7.28; p = .003), and PB > 70% (OR, 4.59; 95%CI, 1.83-11.50; p = .001). Similar results were found when ALP was analyzed as a continuous variable or a category variate according to the cut-off value determined by the receiver operating characteristic curve analysis. Furthermore, the model including clinical factors and ALP significantly improved the predictive power for coronary calcification, spotty calcification, MLA≤4.0 mm2 , and PB > 70%. CONCLUSION: Our findings suggest that ALP may be a potential predictive biomarker for calcification and plaque vulnerability.

miR-194-Loaded Gelatin Nanospheres Target MEF2C to Suppress Muscle Atrophy in a Mechanical Unloading Model.

Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable in vivo, limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.

Refractory hypertension secondary to renal artery stenosis with a honeycomb-like structure.

BACKGROUND: A honeycomb-like structure (HLS) is a rare abnormality characterized by a braid-like appearance. Angiograph and intravascular examination, including coherence tomography and intravascular ultrasound (IVUS), can further confirm the multiple intraluminal channels or honeycomb structure, which can also be described as looking like 'swiss cheese', a 'spider web' or a 'lotus root'. Previous studies have mostly reported this abnormality in coronary arteries, with a few cases in renal arteries. More information about the characteristics and development of HLS is needed. CASE PRESENTATION: A 69-year-old Han man with resistant hypertension received abdominal enhanced computerised tomography and was revealed to have left renal artery stenosis with the possibility of left renal infarction. Renal artery angiography confirmed a 95% stenosis located in the proximal segment of the left renal artery, and the middle segment was blurred with multi-channel-like blood flow. Further IVUS was performed and identified multiple channels surrounded by fibrous tissue. It was a rare case of HLS in the renal artery secondary to the thrombus, with organisation and recanalisation. Balloon dilatation and stent implantation at the proximal segment of the left renal artery were performed successfully. Blood pressure was well controlled after the procedure. CONCLUSIONS: The IVUS findings are helpful for forming interventional therapeutic strategies for HLS lesions in the renal artery.

Searching for conditions of protein self-assembly by protein crystallization screening method.

The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (ß-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: • Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. • This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. • This screening method is fast, high throughput, and easily implemented in an automated system.

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer.

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration-dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen-induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration-resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.

Enhanced efficiency of organic light-emitting devices by using a directly imprinted nanopillared ultrathin metallic electrode.

An ultrathin metal film with high transmittance and conductivity has been demonstrated to be a promising transparent electrode for organic light-emitting devices (OLEDs). However, mediocre surface morphology and continuity of evaporated metal films and the surface plasmon-polaritons (SPPs) energy loss between the metal electrode and organic layer still limit the external quantum efficiency (EQE) of OLEDs. Here, nanoimprint lithography has been directly applied on the ultrathin Au film with underlying uncured photopolymer to fabricate the nanopillared anode. Both the conductivity and transmittance of the nanopillared ultrathin Au film have been improved due to the improvement of continuity and surface smoothness. As we expected, the SPPs mode has been coupled into photons and further extracted from OLEDs by using the nanopillared Au film anode. Finally, 19.2% and 70.1% enhancement of current efficiency were achieved compared to the planar device with ultrathin Au anode and ITO anode, respectively.