HUH Endonuclease: A Sequence-specific Fusion Protein Tag for Precise DNA-Protein Conjugation.

Synthetic DNA-protein conjugates have found widespread applications in diagnostics and therapeutics, prompting a growing interest in developing chemical biology methodologies for the precise and site-specific preparation of covalent DNA-protein conjugates. In this review article, we concentrate on techniques to achieve precise control over the structural and site-specific aspects of DNA-protein conjugates. We summarize conventional methods involving unnatural amino acids and self-labeling proteins, accompanied by a discussion of their potential limitations. Our primary focus is on introducing HUH endonuclease as a novel generation of fusion protein tags for DNA-protein conjugate preparation. The detailed conjugation mechanisms and structures of representative endonucleases are surveyed, showcasing their advantages as fusion protein tag in sequence selectivity, biological orthogonality, and no requirement for DNA modification. Additionally, we present the burgeoning applications of HUH-tag-based DNA-protein conjugates in protein assembly, biosensing, and gene editing. Furthermore, we delve into the future research directions of the HUH-tag, highlighting its significant potential for applications in the biomedical and DNA nanotechnology fields.

Realizing Highly-Ordered Laser-Reduced Graphene for High-Performance Flexible Microsupercapacitor.

Laser reduction of graphene oxide (GO) with direct-write technology is promising to develop miniaturized energy storage devices because of highly flexible, mask-free, and chemical-free merits. However, laser reduction of GO is often accompanied with deflagration (spectacular and violent deoxygenating reaction), leading reduced graphene oxide (rGO) films into brittle and irregular internal structure which is harmful to the applications. Here, a pre-reduction strategy is demonstrated to avoid this deflagration and realize a uniform laser-reduced GO (LrGO) matrix for the application of flexible micro-supercapacitors (MSCs).The pre-reduction process with ascorbic acid decreases the content of oxygen-containing functional groups on GO in advance, and thus relieves gases emission and avoids unconstrained expansion during the laser reduction process. In addition, a self-assembled skeleton with pre-reduced GO (PGO) nanosheets could be constructed which is a more appropriate aforehand framework for laser reduction to establish controllable rGO films with the homogenous porosity. The quasi-solid-state MSCs assembled with laser-reduced PGO exhibit the maximum areal capacitance of 88.32 mF cm-2 , good cycling performance (capacitance retention of 82% after 2000 cycles), and outstanding flexibility (no capacitance degradation after bending for 5000 times). This finding provides opportunities to enhance quality of LrGO which is promising for micro-power devices and beyond.

Synergistic Bimetallic CoCu-Codecorated Carbon Nanosheet Arrays as Integrated Bifunctional Cathodes for High-Performance Rechargeable/Flexible Zinc-Air Batteries.

The unremitting exploration of well-architectured and high-efficiency oxygen electrocatalysts is promising to speed up the surface-mediated oxygen reduction/evolution reaction (ORR/OER) kinetics of rechargeable zinc-air batteries (ZABs). Herein, bimetallic CoCu-codecorated carbon nanosheet arrays (CoCu/N-CNS) are proposed as self-supported bifunctional oxygen catalysts. The integrated catalysts are in situ constructed via a simple sacrificial-templated strategy, imparting CoCu/N-CNS with 3D interconnected conductive pathways, abundant mesopores for electrolyte penetration and ion diffusion, as well as Cu-synergized Co-Nx /O reactive sites for improved catalytic activities. By incorporating a moderate amount of Cu into CoCu/N-CNS, the bifunctional activities can be further increased due to synergistic oxygen electrocatalysis. Consequently, the optimized CoCu/N-CNS realizes a low overall overpotential of 0.64 V for OER and ORR and leads to high-performance liquid ZABs with high gravimetric energy (879.7 Wh kg-1 ), high peak power density (104.3 mW cm-2 ), and remarkable cyclic stability upon 400 h/1000 cycles at 10 mA cm-2 . More impressively, all-solid-state flexible ZABs assembled with the CoCu/N-CNS cathode exhibit superior rate performance and exceptional mechanical flexibility under arbitrary bending conditions. This CoCu/N-CNS monolith holds significant potential in advancing cation-modulated multimetallic electrocatalysts and multifunctional nanocatalysts.

Defective Nb2 C MXene Cocatalyst on TiO2 Microsphere for Enhanced Photocatalytic CO2 Conversion to Methane.

Sustainable and scalable solar-energy-driven CO2 conversion into fuels requires earth-abundant and stable photocatalysts. In this work, a defective Nb2 C MXene as a cocatalyst and TiO2 microspheres as photo-absorbers, constructed via a coulombic force-driven self-assembly, is synthesized. Such photocatalyst, at an optimized loading of defective Nb2 C MXene (5% def-Nb2 C/TiO2 ), exhibits a CH4 production rate of 7.23 µmol g-1  h-1 , which is 3.8 times higher than that of TiO2 . The Schottky junction at the interface improves charge transfer from TiO2 to defective Nb2 C MXene and the electron-rich feature (nearly free electron states) enables multielectron reaction of CO2 , which apparently leads to high activity and selectivity to CH4 (sel. 99.5%) production. Moreover, DFT calculation demonstrates that the Fermi level (EF ) of defective Nb2 C MXene (-0.3 V vs NHE) is more positive than that of Nb2 C MXene (-1.0 V vs NHE), implying a strong capacity to accept photogenerated electrons and enhance carrier lifetime. This work gives a direction to modify the earth-abundant MXene family as cocatalysts to build high-performance photocatalysts for energy production.

Internal and external validation of machine learning-assisted prediction models for mechanical ventilation-associated severe acute kidney injury.

BACKGROUND: Currently, very few preventive or therapeutic strategies are used for mechanical ventilation (MV)-associated severe acute kidney injury (AKI). OBJECTIVES: We developed clinical prediction models to detect the onset of severe AKI in the first week of intensive care unit (ICU) stay during the initiation of MV. METHODS: A large ICU database Medical Information Mart for Intensive Care IV (MIMIC-IV) was analysed retrospectively. Data were collected from the clinical information recorded at the time of ICU admission and during the initial 12 h of MV. Using univariate and multivariate analyses, the predictors were selected successively. For model development, two machine learning algorithms were compared. The primary goal was to predict the development of AKI stage 2 or 3 (AKI-23) and AKI stage 3 (AKI-3) in the first week of patients' ICU stay after initial 12 h of MV. The developed models were externally validated using another multicentre ICU database (eICU Collaborative Research Database, eICU) and evaluated in various patient subpopulations. RESULTS: Models were developed using data from the development cohort (MIMIC-IV: 2008-2016; n = 3986); the random forest algorithm outperformed the logistic regression algorithm. In the internal (MIMIC-IV: 2017-2019; n = 1210) and external (eICU; n = 1494) validation cohorts, the incidences of AKI-23 were 154 (12.7%) and 119 (8.0%), respectively, with areas under the receiver operator characteristic curve of 0.78 (95% confidence interval [CI]: 0.74-0.82) and 0.80 (95% CI: 0.76-0.84); the incidences of AKI-3 were 81 (6.7%) and 67 (4.5%), with areas under the receiver operator characteristic curve of 0.81 (95% CI: 0.76-0.87) and 0.80 (95% CI: 0.73-0.86), respectively. CONCLUSIONS: Models driven by machine learning and based on routine clinical data may facilitate the early prediction of MV-associated severe AKI. The validated models can be found at: https://apoet.shinyapps.io/mv_aki_2021_v2/.

Multicolor Photoactivatable Raman Probes for Subcellular Imaging and Tracking by Cyclopropenone Caging.

Photoactivatable probes, with high-precision spatial and temporal control, have largely advanced bioimaging applications, particularly for fluorescence microscopy. While emerging Raman probes have recently pushed the frontiers of Raman microscopy for noninvasive small-molecule imaging and supermultiplex optical imaging with superb sensitivity and specificity, photoactivatable Raman probes remain less explored. Here, we report the first general design of multicolor photoactivatable alkyne Raman probes based on cyclopropenone caging for live-cell imaging and tracking. The fast photochemically generated alkynes from cyclopropenones enable background-free Raman imaging with desired photocontrollable features. We first synthesized and spectroscopically characterized a series of model cyclopropenones and identified the suitable light-activating scaffold. We further engineered the scaffold for enhanced chemical stability in a live-cell environment and improved Raman sensitivity. Organelle-targeting probes were then generated to achieve targeted imaging of mitochondria, lipid droplets, endoplasmic reticulum, and lysosomes. Multiplexed photoactivated imaging and tracking at both subcellular and single-cell levels was next demonstrated to monitor the dynamic migration and interactions of the cellular contents. We envision that this general design of multicolor photoactivatable Raman probes would open up new ways for spatial-temporal controlled profiling and interrogations in complex biological systems with high information throughput.

The Role of Surgery for Primary Pulmonary Synovial Sarcoma: A Population-Based Study.

INTRODUCTION: The rarity of primary pulmonary synovial sarcoma (PPSS) and the lack of prospective clinical trials resulted in poorly understood treatment modality and clinical outcomes. This study aimed to better understand PPSS based on patients from the Surveillance, Epidemiology, and End Results database. MATERIALS AND METHODS: Clinical and survival data of PPSS patients who were diagnosed during 1989 through 2016 and retrieved from the Surveillance, Epidemiology, and End Results database were studied. Kaplan-Meier analyses and Cox proportional hazards model were applied to evaluate the overall survival (OS) and disease-specific survival (DSS) of PPSS patients. RESULTS: A total of 122 patients with PPSS were included (median age: 50 y). PPSS accounted for 4.5% (122/2741) of total primary synovial sarcoma. Most of the patients were diagnosed as poor or undifferentiated grade (52.0% and 34.0%). Cancer-directed surgery was performed for 74.4% of PPSS patients and 28.2% of patients received radiotherapy. The 1-year, 3-year, 5-year, and 10-year OS rates of PPSS patients were 75.4%, 50.8%, 41.8%, and 39.3%, respectively. Cancer-directed surgery was shown to improve the survival of PPSS patients with localized or regional stage (P < 0.05), yet surgical resection did not prolong the OS and DSS of patients with distant stage (P > 0.1). Postoperational radiotherapy was associated with shortened survival time (P < 0.05). PPSS patients who received lobectomy had statistically prolonged OS and DSS than those with pneumonectomy (P < 0.001). CONCLUSIONS: PPSS is a rare and special subtype of synovial sarcoma. Treatment with lobectomy or sublobar resection alone may contribute to a superior prognosis compared with other managements.

Long non-coding RNA C5orf64 is a potential indicator for tumor microenvironment and mutation pattern remodeling in lung adenocarcinoma.

Understanding the synergistic and antagonistic effects of tumor microenvironment (TME) and tumor mutation pattern on lung adenocarcinoma (LUAD) is urgently needed. Herein, we applied ESTIMATE and CIBERSORT methods to calculate the ratio of immune and stromal components and TIICs proportion of LUAD samples from TCGA database. Immune-related genes were analyzed by Lasso regression analysis and used for ceRNA network construction. A 14-lncRNA immune-related signature was developed, among which C5orf64 was found to be positively correlated with abundances of M2 macrophages, monocytes, eosinophils and neutrophils, but negatively correlated with Tregs and plasma cells. PD-1, PD-L1 and CTLA-4 were demonstrated to be high expressed in high-level C5orf64 groups. However, C5orf64 had a negative correlation with TP53 mutation frequency. A novel model was built based on age, tumor stage and immune-related lncRNA signature. To conclude, lncRNA C5orf64 had potential to be an indicator for TME modulation and tumor mutation pattern remodeling in LUAD.

Development and validation of a nomogram for predicting survival of pulmonary invasive mucinous adenocarcinoma based on surveillance, epidemiology, and end results (SEER) database.

BACKGROUND: Lung cancer remains the leading cause of cancer death globally. In 2015, the cancer classification guidelines of the World Health Organization were updated. The term "invasive mucinous adenocarcinoma (IMA)" aroused people's attention, while the clinicopathological factors that may influence survival were unclear. METHODS: Data of IMA patients was downloaded from SEER database. Kaplan-Meier methods and log-rank tests were used to compare the differences in OS and LCSS. The nomogram was developed based on the result of the multivariable analysis. The discrimination and accuracy were tested by Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses (DCA). Integrated discrimination improvement (IDI) index was used to evaluate the clinical efficacy. RESULTS: According to multivariate analysis, the prognosis of IMAs was associated with age, differentiation grade, TNM stage and treatments. Surgery might be the only way that would improve survival. Area under the curve (AUC) of the training cohort was 0.834and 0.830 for3-and 5-year OS, respectively. AUC for 3-and 5-year LCSS were separately 0.839 and 0.839. The new model was then evaluated by calibration curve, DCA and IDI index. CONCLUSION: Based on this study, prognosis of IMAs was systematically reviewed, and a new nomogram was developed and validated. This model helps us understand IMA in depth and provides new ideas for IMA treatment.

TRIM58 is a prognostic biomarker remodeling the tumor microenvironment in KRAS-driven lung adenocarcinoma.

Aim: To comprehensively analyze the expression profiles of ubiquitin-related genes (URGs) and determine potential biomarkers in KRAS-driven lung adenocarcinoma (LUAD). Materials & methods: Differential expression analyses were performed between KRAS-wild and KRAS-mutant LUAD samples from The Cancer Genome Atlas database, and 34 URGs were screened out. ESTIMATE and CIBERSORT methods were used to calculate the ratio of immune and stromal components. Results & conclusion: TRIM58 was positively correlated with abundances of M2 macrophages and resting mast cells and negatively correlated with follicular helper T-cell abundances in KRAS-driven LUAD. TRIM58 was a potential prognosis-associated indicator for tumor microenvironment modulation and played a key role in TME-specific AS landscapes alterations in KRAS-driven LUAD.

Toward photoswitchable electronic pre-resonance stimulated Raman probes.

Reversibly photoswitchable probes allow for a wide variety of optical imaging applications. In particular, photoswitchable fluorescent probes have significantly facilitated the development of super-resolution microscopy. Recently, stimulated Raman scattering (SRS) imaging, a sensitive and chemical-specific optical microscopy, has proven to be a powerful live-cell imaging strategy. Driven by the advances of newly developed Raman probes, in particular the pre-resonance enhanced narrow-band vibrational probes, electronic pre-resonance SRS (epr-SRS) has achieved super-multiplex imaging with sensitivity down to 250 nM and multiplexity up to 24 colors. However, despite the high demand, photoswitchable Raman probes have yet to be developed. Here, we propose a general strategy for devising photoswitchable epr-SRS probes. Toward this goal, we exploit the molecular electronic and vibrational coupling, in which we switch the electronic states of the molecules to four different states to turn their ground-state epr-SRS signals on and off. First, we showed that inducing transitions to both the electronic excited state and triplet state can effectively diminish the SRS peaks. Second, we revealed that the epr-SRS signals can be effectively switched off in red-absorbing organic molecules through light-facilitated transitions to a reduced state. Third, we identified that photoswitchable proteins with near-infrared photoswitchable absorbance, whose states are modulable with their electronic resonances detunable toward and away from the pump photon energy, can function as the photoswitchable epr-SRS probes with desirable sensitivity (<1 µM) and low photofatigue (>40 cycles). These photophysical characterizations and proof-of-concept demonstrations should advance the development of novel photoswitchable Raman probes and open up the unexplored Raman imaging capabilities.

Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering.

Glycogen, a branched glucose polymer, helps regulate glucose homeostasis through immediate storage and release of glucose. Reprogramming of glycogen metabolism has recently been suggested to play an emerging role in cancer progression and tumorigenesis. However, regulation of metabolic rewiring for glycogen synthesis and breakdown in cancer cells remains less understood. Despite the availability of various glycogen detection methods, selective visualization of glycogen in living cells with high spatial resolution has proven to be highly challenging. Here, we present an optical imaging strategy to visualize glycogen in live cancer cells with minimal perturbation by combining stimulated Raman scattering microscopy with metabolic incorporation of deuterium-labeled glucose. We revealed the subcellular enrichment of glycogen in live cancer cells and achieved specific glycogen mapping through distinct spectral identification. Using this method, different glycogen metabolic phenotypes were characterized in a series of patient-derived BRAF mutant melanoma cell lines. Our results indicate that cell lines manifesting high glycogen storage level showed increased tolerance to glucose deficiency among the studied melanoma phenotypes. This method opens up the possibility for noninvasive study of complex glycogen metabolism at subcellular resolution and may help reveal new features of glycogen regulation in cancer systems.

Development and validation of a prognostic model of resectable small-cell lung cancer: a large population-based cohort study and external validation.

BACKGROUND: Survival outcomes of patients with resected SCLC differ widely. The aim of our study was to build a model for individualized risk assessment and accurate prediction of overall survival (OS) in resectable SCLC patients. METHODS: We collected 1052 patients with resected SCLC from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors were selected by COX regression analyses, based on which a nomogram was constructed by R code. External validation were performed in 114 patients from Shandong Provincial Hospital. We conducted comparison between the new model and the AJCC staging system. Kaplan-Meier survival analyses were applied to test the application of the risk stratification system. RESULTS: Sex, age, T stage, N stage, LNR, surgery and chemotherapy were identified to be independent predictors of OS, according which a nomogram was built. Concordance index (C-index) of the training cohort were 0.721, 0.708, 0.726 for 1-, 3- and 5-year OS, respectively. And that in the validation cohort were 0.819, 0.656, 0.708, respectively. Calibration curves also showed great prediction accuracy. In comparison with 8th AJCC staging system, improved net benefits in decision curve analyses (DCA) and evaluated integrated discrimination improvement (IDI) were obtained. The risk stratification system can significantly distinguish the ones with different survival risk. We implemented the nomogram in a user-friendly webserver. CONCLUSIONS: We built a novel nomogram and risk stratification system integrating clinicopathological characteristics and surgical procedure for resectable SCLC. The model showed superior prediction ability for resectable SCLC.

Prognostic effect of a risk index model in postoperative non-small-cell lung cancer patients.

Aim: Predicting the prognostic outcome of a single case among postoperative non-small-cell lung cancer (NSCLC) patients is difficult. We created a precise prognostic model to assess the condition and prognosis of postoperative NSCLC patients. Methods: We combined eight prognostic indicators (age, prothrombin time, international normalized ratio, globulin, albumin-to-globulin ratio, tumor diameter, number of positive lymph nodes and number of dissected lymph nodes) to construct a new risk index (RI) model. Results: The best cut-off value was -1.86 (area under the curve: 0.719). The overall survival of postoperative NSCLC patients decreased as the RI increased (p < 0.001). Conclusion: This RI model can assist clinicians in screening high-risk groups and developing treatment and follow-up plans for postoperative NSCLC patients.

Survival nomogram for patients with initially diagnosed metastatic non-small-cell lung cancer: a SEER-based study.

Aim: Prognosis of patients with metastatic non-small-cell lung cancer differ widely. Methods: All patients were randomly divided into training or validation cohort. Cox-regression analyses were conducted to select independent predictors. We built a nomogram by R code and evaluated the accuracy and the reliability of the model using C-index, calibration curves and decision curve analyses. We made a risk classification system based on the nomogram. Results: In the validation cohort, C-index was 0.729 and 0.738 for 1- and 2-year overall survival. Calibration plots and decision curve analyses presented great prognostic accuracy and clinical applicability. Its prognostic accuracy preceded the American Joint Committee on Cancer staging with evaluated integrated discrimination improvement. Conclusion: The model can be a practical tool in treatment decision and individual counseling.

Blood pressure and hypertension prevalence among oldest-old in China for 16 year: based on CLHLS.

BACKGROUND: There were little national data on hypertension based on the oldest-old, and lack of information on chronological changes. This study aimed to describe trends of blood pressure (BP) levels and hypertension prevalence for the past 16 years among the oldest-old in China. METHODS: All the oldest-old who had participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 1998 to 2014 with information about BP levels and hypertension were included in the analysis. RESULTS: There was fluctuation over the past 16 years for both SBP and DBP levels. The mean SBP level decreased from 148.4 ± 24.4 mmHg in 1998 to 130.8 ± 18.7 mmHg in 2005, and then increased to 139.7 ± 22.0 mmHg in 2014. The mean DBP level decreased from 84.3 ± 13.4 mmHg in 1998 to 78.9 ± 11.7 mmHg in 2008, and then increased to 79.7 ± 11.8 mmHg in 2014. The hypertension prevalence increased from 43.1 to 56.5% for the 16 years. The prevalence of isolated systolic hypertension was lowest in 2002-2005 (14.3%), and then increased to 30.7% in 2014. Multivariate logistic regression showed that older age, lower education and economic level, without health insurance were associated with higher hypertension prevalence. CONCLUSIONS: There was a significant increase in hypertension prevalence among the Chinese oldest-old from 1998 to 2014. Greater efforts are needed for hypertension prevention among this specific population.

Urban-rural comparisons in health risk factor, health status and outcomes in Tianjin, China: A cross-sectional survey (2009-2013).

OBJECTIVE: To investigate the urban-rural disparities in health risk factors, health status and outcomes in Tianjin, China and to make an international comparison with urban-rural health in Australia. DESIGN: A descriptive analytical cross-sectional survey. SETTING: Mobile research teams conducted door-to-door field surveys of each house or department. The teams included local administrative staff and Tianjin Center for Disease Control and Prevention's epidemiologists, clinicians and laboratory technicians. PARTICIPANTS: A total of 25 288 residents were interviewed and clinically observed, including 8583 urban residents and 16 705 rural residents. MAIN OUTCOME MEASURE: Health risk factors, health status and outcomes. RESULTS: The age structure in urban areas of Tianjin was growing older. Rural residents received less high school education and university education than did urban residents. Urban residents had higher medical insurance coverage and paid more out-of-pocket medical expenditures than did rural residents. The prevalence of smoking and the crude alcohol consumption rate were higher in rural areas than in urban areas. Rural residents had feelings of higher self-satisfaction concerning their health status than did urban residents. The prevalence of hypertensive disease, type 2 diabetes and heart, stroke and vascular diseases were significantly lower in rural areas than in urban areas. The incidence rate of serious injuries resulting from traffic accidents was significantly higher in rural areas than in urban areas. CONCLUSION: Contrary to Australian urban-rural survey outcomes, the health status and outcomes of residents in rural areas of Tianjin seemed to be better than those of their counterparts in urban areas. The underlying determinants of these outcomes need to be explored with further study.

An inflammation-related nomogram for predicting the survival of patients with non-small cell lung cancer after pulmonary lobectomy.

BACKGROUND: Emerging inflammatory response biomarkers are developed to predict the survival of patients with cancer, the aim of our study is to establish an inflammation-related nomogram based on the classical predictive biomarkers to predict the survivals of patients with non-small cell lung cancer (NSCLC). METHODS: Nine hundred and fifty-two NSCLC patients with lung cancer surgery performed were enrolled into this study. The cutoffs of inflammatory response biomarkers were determined by Receiver operating curve (ROC). Univariate and multivariate analysis were conducted to select independent prognostic factors to develop the nomogram. RESULTS: The median follow-up time was 40.0 months (range, 1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P = 0.045) was selected to establish the nomogram which could predict the 5-year OS probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve displayed an optimal agreement between the actual observed outcomes and the predictive results. CONCLUSIONS: Neutrophil to lymphocyte ratio was shown to be a valuable biomarker for predicting survival of patients with NSCLC. The addition of neutrophil to lymphocyte ratio could improve the accuracy and predictability of the nomogram in order to provide reference for clinicians to assess patient outcomes.

Loss of ß-arrestin1 expression predicts unfavorable prognosis for non-small cell lung cancer patients.

We aimed to study the expression status of ß-arrestin1 in non-small cell lung cancer (NSCLC) specimens and its clinicopathologic significance. The correlation between ß-arrestin1 and the tumor migration biomarker E-cadherin, as well as smoking index were studied. A total of 152 patients with NSCLC who undergone surgery were enrolled. Altogether, 88 lung squamous cell lung cancer (SCC) specimens and 64 adenocarcinoma (ADC) specimens were tested for immunohistochemistry. Patients' survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent prognostic factors. Spearman rank correlation test was used to show data associations. For SCC patients, the expression of ß-arrestin1 was either lost (56 of 88, 63.6 %) or low (32 of 88, 36.4 %), which was significantly and negatively associated with E-cadherin expression (P = 0.017). The similar correlation existed between smoking index and ß-arrestin1 expression (P = 0.044). For ADC patients, the deletion of ß-arrestin1 expression was rare (4 of 64, 6.3 %). Loss of ß-arrestin1 expression indicated poorer survival for both SCC (P = 0.026) and ADC patients (P = 0.006). ß-arrestin1 expression was detected in the other ADC specimens but showed no significant correlation with survival. In SCC patients, the loss expression of ß-arrestin1 was frequently observed, and ß-arrestin1 expression was significantly correlated with the smoking index and E-cadherin expression, which all indicated ß-arrestin1's significant clinicopathologic role. However, ß-arrestin1 was expressed in most ADC patients, but its clinicopathologic role seemed to be obscure and might need further exploration.

Small quinolinium-based enzymatic probes via blue-to-red ratiometric fluorescence.

A small fluorescence ratiometric probe consisting of a single dye species, N-methyl-6-hydroxyquinolinium (MHQ), and coupled enzymatic substrates, exhibits a dramatic colour change (deep blue to red) and possesses a huge response ratio (over 2000 fold) upon specific recognition of target enzymes. Such dramatic responses are attributed to the excited-state proton transfer processes of MHQ molecules in water. Here the detection of ß-galactosidase and porcine pancreatic lipase is successfully demonstrated and this class of molecules has the potential to be developed as a "naked-eye" probe in vitro.