Hollow CeO2-Based Nanozyme with Self-Accelerated Cascade Reactions for Combined Tumor Therapy.

Nanozymes have obvious advantages in improving the efficiency of cancer treatment. However, due to the lack of tissue specificity, low catalytic efficiency, and so on, their clinical applications are limited. Herein, the nanoplatform CeO2@ICG@GOx@HA (CIGH) with self-accelerated cascade reactions is constructed. The as-prepared nanozyme shows the superior oxidase (OXD)-like, superoxide dismutase (SOD)-like, catalase (CAT)-like and peroxidase (POD)-like activities. At the same time, under 808 nm near-infrared (NIR) irradiation, the photodynamic and photothermal capabilities are also significantly enhanced due to the presence of indocyanine green (ICG). We demonstrate that the nanozyme CIGH can efficiently accumulate in the tumor and exhibit amplified cascade antitumor effects with negligible systemic toxicity through the combination of photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT) and starvation therapy. The nanozyme prepared in this study provides a promising candidate for catalytic nanomedicines for efficient tumor therapy.

Cu+-doped lead-free double perovskite quantum dots for enhancing the photovoltaic performance of carbon-based Cs2AgInCl6 perovskite solar cells.

Lead-free double perovskite solar cells (PSCs) have received widespread attention because of their non-toxic nature and three-dimensional structure. However, their photovoltaic efficiency is limited by their large bandgap, including indirect or direct forbidden. Herein, Cu+ ions are incorporated into Cs2AgInCl6 double perovskite quantum dots, following which the bandgap is effectively decreased from 3.6 to 2.9 eV. Meanwhile, a facile method of drop-coating is employed to fabricate Cs2AgInCl6 films and carbon electrodes. A carbon electrode derived from a by-product of the cane sugar industry (molasses) is used to replace the expensive hole-transport materials and metal electrodes. A 0.5% Cu+-doped Cs2AgInCl6, device fabricated using carbon-based PSCs with a stacked-architecture achieves a power conversion efficiency of 1.77%, which is 2.9 times higher than that of the original device, and displays a better stability compared with that of the control one. This study provides guidance for preparing PSCs using a low-cost, facile strategy.

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

Bioinspired Robust Water Repellency in High Humidity by Micro-meter-Scaled Conical Fibers: Toward a Long-Time Underwater Aerobic Reaction.

Superhydrophobic surfaces have suffered from being frequently penetrated by micro-/nano-droplets in high humidity, which severely deteriorates their water repellency. So far, various biological models for the high water repellency have been reported, which, however, focused mostly on the structural topology with less attention on the dimension character. Here, we revealed a common dimension character of the superhydrophobic fibrous structures of both Gerris legs and Argyroneta abdomens, featured as the conical topology and the micro-meter-scaled cylindrical diameter. In particular, it can be expressed by using a parameter of rp/l > 0.75 µm (r, l, and p are the radius, length, and apex spacing between fibers, respectively). Drawing inspiration, we developed a superhydrophobic micro-meter-scaled conical fiber array with a rather high rp/l value of 0.85 µm, which endows ultra-high water repellency even in high humidity. The micro-meter-scale asymmetric confined space between fibers enables generating a big difference in the Laplace pressure enough to propel the condensed dews away, while the tips help pin the air pocket underwater with a rather long life over 41 days. Taking advantage, we demonstrated a sustainable underwater aerobic reaction where oxygen was continuously supplied from the trapped air pocket by a gradually diffusing process. As a parameter describing both the dimension character and structural topology, the rp/l offers a new perspective for fabricating superhydrophobic fibrous materials with robust water repellency in high humidity, which inspires the innovative underwater devices with a robust anti-wetting performance.

Identification of risk factors for incident cervical insufficiency in nulliparous and parous women: a population-based case-control study.

BACKGROUND: Cervical insufficiency is one of the underlying causes of late miscarriage and preterm birth. Although many risk factors have been identified, the relative magnitude of their association with risk in nulliparous versus parous women has not been well demonstrated, especially for incident cervical insufficiency (ICI). The aim of this study was to investigate and compare the magnitude of the association of ICI with predictive factors in nulliparous and parous women, and to further investigate various aspects of obstetric history for parous women. METHODS: Pregnant women with a first diagnosis of cervical insufficiency were compared to a random sample of control pregnancies from women with no diagnosis by using Swedish national health registers. Demographic, reproductive, and pregnancy-specific factors were compared in case and control pregnancies, and relative risks presented as odds ratios (OR), stratified by nulliparous/parous. Independent associations with ICI were estimated from multivariable logistic regression. Associations with obstetric history were further estimated for multiparous women. RESULTS: A total of 759 nulliparous ICI cases and 1498 parous cases were identified during the study period. Multifetal gestation had a strong positive association with ICI in both groups, but of much larger magnitude for nulliparous women. The number of previous miscarriages was also a much stronger predictor of risk in nulliparous women, especially for multifetal pregnancies. History of preterm delivery (<37 weeks' gestation) was an independent predictor for parous women, and for those whose most recent delivery was preterm, the association with ICI increased with each additional week of prematurity. A previous delivery with prolonged second stage of labor or delivery of a very large infant were both inversely associated with risk of ICI in the current pregnancy. CONCLUSIONS: The differences in importance of predictive risk factors for incident cervical insufficiency in nulliparous and parous women can help resolve some of the inconsistencies in the literature to date regarding factors that are useful for risk prediction. Stratifying on parity can inform more targeted surveillance of at-risk pregnancies, enable the two groups of women to be better informed of their risks, and eventually inform screening and intervention efforts.

Risk factors for non-positional obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: To explore the main risk factors for non-positional obstructive sleep apnea (NPOSA). METHODS: A total of 560 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) were divided into non-positional obstructive sleep apnea (NPOSA) and positional obstructive sleep apnea (POSA) groups. All patients were assessed by the Friedman staging system and anthropometry before overnight polysomnography. Blood tests were performed to determine the fasting blood glucose level and lipid profile. Forward logistic regression analysis was performed to evaluate the effects of all parameters on positional dependency. RESULTS: The study sample consisted of 318 NPOSA patients and 242 POSA patients (88% and 85% were men, respectively). The mean apnea-hypopnea index (AHI) was 57.0 events/h in the NPOSA group, compared with 25.7 events/h in the POSA group. The POSA group had a significantly smaller neck circumference (NC), waist circumference (WC), hip circumference (HC), lower body mass index (BMI), AHI, fasting blood glucose, and apolipoprotein-B (apoB) levels than did the NPOSA group (all, P < 0.01). The minimal nocturnal oxyhemoglobin saturation (minSpO2) and apoB/apoA ratio were higher in the POSA group than in the NPOSA group (both, P < 0.001). The AHI, minSpO2, WC, and fasting blood glucose level were included in the logistic regression models. CONCLUSION: The AHI, WC, minSpO2, and fasting blood glucose level are the main independent risk factors for NPOSA.

DNA methylation patterns of SOCS1 gene in peripheral blood identifies risk loci associated with bladder cancer based on principal component analysis.

Bladder cancer (BCa) is a common carcinoma of the urinary tract, which occurs in the bladder mucosa. In recent years, people have recognized that epigenetic changes such as DNA methylation play important roles in the development of BCa but the specific mechanism is unclear. In this study, we detected the methylation rates in the SOCS1 gene of 490 subjects (including 247 patients with BCa and 243 healthy controls) using the MassARRAY EpiTYPER system. Principal component analysis (PCA) was conducted with the aim of identifying common underlying patterns that could explain the largest part of common variance in methylation across units. A logistic regression model was used to assess the relation of SOCS1 methylation patterns with factors related to BCa risk. The methylation rates varied for different CpG units and were significantly different in BCa patients compared to controls. Six principal component factors were extracted by combining initial eigenvalue, explanatory power, and Scree Plot. After adjusting for age, gender, family history of bladder cancer, smoking, and drinking, we observed that Factor 1 (OR=0.051, 95% CI: 0.015-0.178, p<0.001), Factor 2 (OR=0.146, 95% CI: 0.073-0.295, p<0.001), Factor 3 (OR=0.346, 95% CI: 0.198-0.606, p<0.001), and Factor 4 (OR=0.270, 95% CI: 0.135-0.537, p<0.001) were associated with BCa. Based on follow-up results, we found that the 1-, 3-, 5-year survival rates in the hypermethylated group were lower than in the hypomethylated group. We found that several CpG units in methylation patterns were associated with the incidence of BCa showing the important DNA methylation patterns for BCa pathogenesis. Our findings provided new insights into understanding this disease and new potential targets for therapeutic intervention for BCa patients in the future.

Sea level nocturnal minimal oxygen saturation can accurately detect the presence of obstructive sleep apnea in a population with high pretest probability.

PURPOSE: To evaluate whether a predictive model based on nocturnal minimal oxygen saturation (SpO2) alone can accurately detect the presence of obstructive sleep apnea (OSA) in a population with suspected OSA. METHODS: A total of 4297 participants with suspected OSA were enrolled in this study, and laboratory-based polysomnography (PSG) tests were performed at sea level in all subjects. Nocturnal minimal SpO2 was obtained automatically as part of the PSG test. Stratified sampling was used to divide the participants' data into the training set (75%) and the test set (25%). An OSA detection model based on minimal SpO2 alone was created using the training set data and its performance was evaluated using the independent test set data ("hold-out" evaluation). Gender-specific models, and models based on minimal SpO2 in combination with other predictive factors (age, body mass index, waist-to-hip ratio, snoring grade, Epworth Sleepiness Scale score, and comorbidities), were also created and compared in terms of OSA detection performance. RESULTS: The prevalence of OSA was 85.6% in our study population. The models including multiple predictors, and the gender-specific models, failed to outperform the model based solely on minimal SpO2, which showed good predictive performance (C statistic, 0.922) having an overall accuracy rate of 0.86, sensitivity of 0.87, specificity of 0.84, positive predictive value of 0.97, and positive likelihood ratio of 5.34. In addition, the model based on minimal SpO2 alone could also accurately predict the presence of moderate-to-severe OSA and severe OSA, with C statistics of 0.914 and 0.900, respectively. CONCLUSIONS: A predictive model based on nocturnal minimal SpO2 alone may be an alternative option to detect the presence of OSA in a high-risk population when standard diagnostic tests are unavailable.

The association between obesity indices and obstructive sleep apnea is modified by age in a sex-specific manner.

BACKGROUND: The beneficial effects of weight reduction on obstructive sleep apnea (OSA) are highly variable. Whether or not the variability is associated with the effects of age and sex remains unclear. This study examined this issue with large cross-sectional data. METHOD: Anthropometric measurements, polysomnographic variables, biochemical indicators, and medical history were collected for each participant. Multivariable linear regression with interaction terms was used to estimate the modification effect of age on the associations between OSA severity (assessed by apnea-hypopnea index, AHI) with obesity indices (body mass index, BMI; neck circumference, NC; waist circumference, WC; waist-to-hip ratio, WHR) in a sex-specific manner, and vice versa. To facilitate interpretation of the results, participants were further classified into six subpopulations according to both sex and age, and population-specific beta-coefficients were calculated and compared. RESULTS: A total of 5756 adults (4600 men) with suspected OSA were included in the study. BMI, NC, WC, and WHR were all positively correlated with AHI after adjusting for potential confounders in all populations. In men, these associations were much stronger and more significant in younger than older individuals (P for interaction < 0.001). For example, a 10% increase in BMI was independently associated with a 32% increase in AHI for men < 40 years old, whereas the corresponding increases were 21% and 17% for men 40-60 and > 60 years old, respectively. By contrast, no modification effect of age was observed in women (P for interaction > 0.05). A 10% increase in BMI was associated with 26%, 27%, and 24% increases in AHI for women < 40, 40-60, and > 60 years old, respectively. CONCLUSIONS: Age modifies the associations between obesity indices and OSA severity in a sex-specific manner. These findings may broaden the understanding of age- and sex-related heterogeneities in the pathogenic role of obesity in OSA, and may be beneficial for individualized risk evaluation and treatment management for patients with OSA.

Direct Writing Large-Area Multi-Layer Ultrasmooth Films by an All-Solution Process: Toward High-Performance QLEDs.

With increasing the film area/layer, deteriorating in both smoothness and uniformity of thin-films frequently happen, which remains a barrier for making large-area quantum dot light-emitting diodes (QLEDs) by solution processes. Here, we demonstrated a facile all-solution process guided by the conical fiber array to write multi-layer ultrasmooth thin-films directly in centimeter scale. The side-by-side fibrous array helps to align surface tensions at the tri-phase contact line to facilitate large-area homogeneous deposition, which was verified by theoretical simulation. The Laplace pressure along individual conical fiber contributes to the steady liquid transfer. Thin-films with small roughness (<2.03 nm) and large-area (2×2 cm2 ) uniformity were prepared sequentially on the target substrate, leading to large-area high-performance QLEDs. The result offers new insights for fabricating large-area high-performance thin-film devices.

Activated hepatic stellate cells promote angiogenesis in hepatocellular carcinoma by secreting angiopoietin-1.

Angiogenesis is the central pathological process in hepatocellular carcinoma (HCC), and its progression is affected by tumor cells and the microenvironment. Activated hepatic stellate cells (aHSCs) are the most significant stromal cells involved in HCC. This study was aimed to explore the effects and mechanisms of aHSCs on angiogenesis in HCC. We isolated primary hepatoma cells, aHSCs, and hepatic vascular endothelial cells from human HCC samples. Then, we performed a novel in vitro assay and in vivo experiment in a nude mouse HCC model to investigate the functions of aHSCs on angiogenesis in HCC. Our results demonstrated that aHSCs are the primary sources of angiopoietin-1 (Ang-1) in human HCC in vitro, and aHSCs could promote hepatic vascular endothelial cell (HVEC) growth by secreting Ang-1. Furthermore, aHSCs could induce HVEC microtubule formation, and this ability was reduced when Ang-1 expression was silenced in aHSCs. In addition, CD34 expression in a nude mouse HCC model was downregulated when Ang-1 messenger RNA was silenced in aHSCs. Our data also indicated that HSC Ang-1 expression could be inhibited by overexpressing Raf kinase inhibitor protein. Therefore, we suggest that aHSCs promote angiogenesis through secreting Ang-1, potentially providing an interesting target for antiangiogenic therapies for HCC.

Aberrant Methylation of Suppressor of Cytokine Signaling 1 (SOCS1) Gene as a Biomarker for Early Prediction and Diagnosis of Bladder Cancer.

BACKGROUND: SOCS1 protein, the negative regulatory protein of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway, may inhibit signaling of JAK-STAT pathway by several cytokines and has tumor suppressor activity. Methylation of CpG island in the promoter region of SOCS1 gene has often been shown to inactivate the SOCS1 gene in certain human cancers. However, the precise role of SOCS1 in bladder cancer is unclear. METHODS: Two hundred forty-seven patients with BCa and 243 healthy controls were enrolled from Tumour Hospital Affiliated to Harbin Medical University, Hongqi Hospital Affiliated to Mudanjiang Medical University, and Mudanjiang Tumour Hospital from September 2013 to March 2019. The methylation rate in the promoter region of the SOCS1 among all participants were detected using the MassARRAY EpiTYPER system. A ROC curve was set out to analyze SOCS1 gene promoter CpG island methylation for BCa diagnosis. RESULTS: There was a significantly higher methylation rate in BCa compared to controls. Then we assessed the methylation rate of different CpG islands in SOCS1 gene among BCa cases and normal controls. Methylation rate was shown to vary among different CpG islands. The methylation rates of CpG islands were shown to vary among different grades. We observed that the methylation rate of different CpG islands vary according to pathological grades. CONCLUSIONS: Our study demonstrates that aberrant methylation of CpG island in the promoter region of SOCS1 gene may be involved in occurrence, progression, and prognosis of BCa and, thus, may serve as an independent diagnosis and prognostic biomarker.

Impact of right-to-left shunt and transcatheter closure on the clinical features of migraine.

Objectives: In this study, we aimed to explore the influence of right-to-left shunt (RLS) presence on the clinical features of migraine and to follow-up on the post-operative curative effect of transcatheter patent foramen ovale (PFO) closure on migraine features.Methods: A total of 103 migraine patients were divided into a mild volume RLS group, moderate volume RLS group, large volume RLS group and non-RLS group in accordance with contrast enhancement transcranial Doppler (c-TCD) findings. The Visual Analogue Scale (VAS) score, migraine frequency, migraine duration, migraine disability assessment (MIDAS) and headache impact test-6 (HIT-6) scores were compared amongst the different groups. A total of 39 patients with moderate or large RLS received transcatheter PFO closure and those patients were followed up by the same criteria.Results: The attack frequency, HIT-6 and MIDAS scores amongst the migraine patients with moderate or large RLS were significantly higher than those in patients from the mild RLS group and non-RLS group (p < .05). The transcatheter closure was successful in all patients (n = 39), and no post-operative complications were observed during the hospitalisation and follow-up period. The differences in VAS, HIT-6 and MIDAS scores as well as the headache duration were statistically significant amongst patients before and after PFO closure (p < .05).Conclusions: Moderate to large RLS significantly influenced the clinical features of migraine, and transcatheter PFO closure could significantly relieve headache symptoms in migraine patients with PFO.

Inhibition of Yeast-to-Hypha Transition and Virulence of Candida albicans by 2-Alkylaminoquinoline Derivatives.

A rapid increase in Candida albicans infection and drug resistance has caused an emergent need for new clinical strategies against this fungal pathogen. In this study, we evaluated the inhibitory activity of a series of 2-alkylaminoquinoline derivatives against C. albicans isolates. A total of 28 compounds were assessed for their efficacy in inhibiting the yeast-to-hypha transition, which is considered one of the key virulence factors in C. albicans Several compounds showed strong activity to decrease the morphological transition and virulence of C. albicans cells. The two leading compounds, compound 1 (2-[piperidin-1-yl]quinolone) and compound 12 (6-methyl-2-[piperidin-1-yl]quinoline), remarkably attenuated C. albicans hyphal formation and cytotoxicity in a dose-dependent manner, but they showed no toxicity to either C. albicans cells or human cells. Intriguingly, compound 12 showed an excellent ability to inhibit C. albicans infection in the mouse oral mucosal infection model. This leading compound also interfered with the expression levels of hypha-specific genes in the cyclic AMP-protein kinase A and mitogen-activated protein kinase signaling pathways. Our findings suggest that 2-alkylaminoquinoline derivatives could potentially be developed as novel therapeutic agents against C. albicans infection due to their interference with the yeast-to-hypha transition.

Efficacy of Compounds Isolated from Streptomyces olivaceus against the Morphogenesis and Virulence of Candida albicans.

Candida albicans is a type of commensal fungi which causes serious infections in immunocompromised patients and contributes to high mortality. In the present study, we identified that the extract from Streptomyces olivaceus SCSIO T05 inhibited hypha and biofilm formation of C. albicans. Seven compounds were isolated and evaluated for their effects on the biological functions and virulence of C. albicans. Two leading compounds, compound 1 (sorbicillin) and compound 2 (3-methyl-N-(2'-phenethyl)-butyrylamide) were identified as exhibiting strong activity against C. albicans morphological transition, adhesion activity, cytotoxicity, and adhesion to human cells, in a dose-dependent manner. Notably, compound 2 inhibited C. albicans infection in mouse oral mucosal models. Transcriptomic analysis and real-time PCR results revealed that compound 2 most likely inhibited the biological functions of C. albicans cells by regulating the expression levels of HWP1, TEC1, ALS1, IFD6, and CSH1, which are associated with filament formation and cell adhesion. Our results suggest that the candidate compounds present excellent efficacy against C. albicans pathogenicity and that they can be developed as potential options for the clinical treatment of candidiasis.

Safe and Robust Mobile Robot Navigation in Uneven Indoor Environments.

Complex environments pose great challenges for autonomous mobile robot navigation. In this study, we address the problem of autonomous navigation in 3D environments with staircases and slopes. An integrated system for safe mobile robot navigation in 3D complex environments is presented and both the perception and navigation capabilities are incorporated into the modular and reusable framework. Firstly, to distinguish the slope from the staircase in the environment, the robot builds a 3D OctoMap of the environment with a novel Simultaneously Localization and Mapping (SLAM) framework using the information of wheel odometry, a 2D laser scanner, and an RGB-D camera. Then, we introduce the traversable map, which is generated by the multi-layer 2D maps extracted from the 3D OctoMap. This traversable map serves as the input for autonomous navigation when the robot faces slopes and staircases. Moreover, to enable robust robot navigation in 3D environments, a novel camera re-localization method based on regression forest towards stable 3D localization is incorporated into this framework. In addition, we utilize a variable step size Rapidly-exploring Random Tree (RRT) method which can adjust the exploring step size automatically without tuning this parameter manually according to the environment, so that the navigation efficiency is improved. The experiments are conducted in different kinds of environments and the output results demonstrate that the proposed system enables the robot to navigate efficiently and robustly in complex 3D environments.

Overexpression of dedicator of cytokinesis 2 correlates with good prognosis in colorectal cancer associated with more prominent CD8+ lymphocytes infiltration: a colorectal cancer analysis.

Recently, dedicator of cytokinesis 2 (DOCK2) has been reportedly exhibited high mutation prevalence in the Asian colorectal cancer (CRC) cohort. However, the expression pattern of DOCK2 and its clinical significance in CRC were still unknown. To characterize the role of DOCK2, a tissue microarray (TMA) containing 481 archived paraffin-embedded CRC specimens was performed by immunohistochemistry. Among which, 54 primary CRC tissues showed high expression of DOCK2 protein, while others were negative. Moreover, DOCK2 expression was positively associated with invasion depth (P < .001) and tumor size (P = .016). Significantly, Kaplan-Meier survival analysis revealed that patients with higher DOCK2 expression had a longer overall survival time (P = .017). Furthermore, univariate and multivariate Cox regression analysis confirmed that DOCK2 is an independent prognostic marker in CRC (P = .049,; HR, 0.519; 95% CI, 0.270 to 0.997). In addition, we observed a strong correlation between the infiltration of CD8+ T lymphocytes and DOCK2 expression (P = .0119). Our findings demonstrated that overexpressed DOCK2 might involve in recruiting CD8+ T lymphocytes and serve as a novel prognostic indicator and indicated a potential therapeutic strategy by restoring DOCK2 for CRC.

Ultrasmooth Quantum Dot Micropatterns by a Facile Controllable Liquid-Transfer Approach: Low-Cost Fabrication of High-Performance QLED.

Fabrication of a high quality quantum dot (QD) film is essentially important for a high-performance QD light emitting diode display (QLED) device. It is normally a high-cost and multiple-step solution-transfer process where large amounts of QDs were needed but with only limited usefulness. Thus, developing a simple, efficient, and low-cost approach to fabricate high-quality micropatterned QD film is urgently needed. Here, we proposed that the Chinese brush enables the controllable transfer of a QD solution directly onto a homogeneous and ultrasmooth micropatterned film in one step. It is proposed that the dynamic balance of QDs was enabled during the entire solution transfer process under the cooperative effect of Marangoni flow aroused by the asymmetric solvent evaporation and the Laplace pressure different by conical fibers. By this approach, QD nanoparticles were homogeneously transferred onto the desired area on the substrate. The as-prepared QLED devices show rather high performances with the current efficiencies of 72.38, 26.03, and 4.26 cd/A and external quantum efficiencies of 17.40, 18.96, and 6.20% for the green, red, and blue QLED devices, respectively. We envision that the result offers a low-cost, facile, and practically applicable solution-processing approach that works even in air for fabricating high-performance QLED devices.

Low serum gastrin associated with ER+ breast cancer development via inactivation of CCKBR/ERK/P65 signaling.

BACKGROUND: Gastrin is an important gastrointestinal hormone produced primarily by G-cells in the antrum of the stomach. It normally regulates gastric acid secretion and is implicated in a number of human disease states, but how its function affects breast cancer (BC) development is not documented. The current study investigated the suppressive effects of gastrin on BC and its underlying mechanisms. METHODS: Serum levels of gastrin were measured by enzyme-linked immunosorbent assay (ELISA) and correlation between gastrin level and development of BC was analyzed by chi-square test. Inhibitory effects of gastrin on BC were investigated by CCK-8 assay and nude mice models. Expressions of CCKBR/ERK/P65 in BC patients were determined through immunohistochemistry (IHC) and Western blot. Survival analysis was performed using the log-rank test. RESULTS: The results indicated that the serum level of gastrin in BC patients was lower compared with normal control. Cellular and molecular experiments indicated that reduction of gastrin is associated with inactivation of cholecystokinin B receptor (CCKBR)/ERK/P65 signaling in BC cells which is corresponding to molecular type of estrogen receptor (ER) positive BC. Furthermore, we found that low expression of gastrin/CCKBR/ERK /P65 was correlated to worse prognosis in BC patients. Gastrin or ERK/P65 activators inhibited ER+ BC through CCKBR-mediated activation of ERK/P65. Moreover, combination treatment with gastrin and tamoxifen more efficiently inhibited ER+ BC than tamoxifen alone. CONCLUSIONS: We concluded that low serum gastrin is related to increased risk of ER+ BC development. The results also established that CCKBR/ERK/P65 signaling function is generally tumor suppressive in ER+ BC, indicating therapies should focus on restoring, not inhibiting, CCKBR/ERK/P65 pathway activity.

Decreased Urine miR-199-3p may be a Potential Biomarker for Diabetic Nephropathy via Targeting Zinc Finger E-box-Binding Protein 1.

BACKGROUND: The current study aims to evaluate the expression pattern changes of miR-199-3p in diabetic nephropathy (DN) patients and explore whether it could be used as a potential biomarker. METHODS: Real time PCR analysis was performed to examine the level of miR-199-3p in normoalbuminuria group (diabetes mellitus [DM]), microalbuminuria group (DNE), macroalbuminuria group (DNC), and healthy controls. ROC analysis was carried out to determine whether urine miR-199-3p could be used as a potential biomarker. Dual luciferase reporter assay was used to identify the target gene of miR-199-3p. RESULTS: Here we showed novel data that urine miR-199-3p was significantly decreased in the diabetes patients compared to healthy controls. Meanwhile, urine miR-199-3p was lowest in DNC group, lower in DNE group, but was relatively higher in DM group. Additionally, urine miR-199-3p level positively correlated with UAE level in both DNE group and DNC group. ROC analysis showed that the urine miR-199-3p may be used to differentiate DNE and DNC subjects from healthy controls and DM group. Besides, miR-199-3p could significantly suppress the relative luciferase activity of pmirGLO-ZEB1, indicating ZEB1 was a target gene of miR-199-3p. CONCLUSIONS: In summary, for the first time, we showed novel data that decreased urinary miR-199-3p could screen DN patients from DM patients and healthy controls, which may be a non-invasive biomarker for DN patients.