A label-free activatable biosensor for in situ detection of exosomal microRNAs based on DNA-AgNCs and hairpin type nucleic acid probes.

Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situ detection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situ exosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situ exosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situ red fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 107 particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situ detection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.

Establishment and Reliability Evaluation of Prognostic Models in Diabetic Foot.

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

From non-targeted to targeted GC-MS metabolomics strategy for identification of TCM preparations containing natural and artificial musk.

BACKGROUND: Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge. METHOD: A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC-MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC-MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS). RESULTS: Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3. CONCLUSION: Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations.

A randomized controlled trial of emergency LCBDE + LC and ERCP + LC in the treatment of choledocholithiasis with acute cholangitis.

INTRODUCTION: Emergency biliary drainage is the basic treatment for acute cholangitis caused by choledocholithiasis. AIM: To compare the effectiveness and safety of emergency laparoscopic common bile duct exploration combined with laparoscopic cholecystectomy (LCBDE + LC) and endoscopic retrograde cholangiopancreatography combined with laparoscopic cholecystectomy (ERCP + LC) for the treatment of choledocholithiasis combined with grade I or II acute cholangitis. MATERIAL AND METHODS: A total of 80 patients were enrolled in the study, with 40 cases in each group. A prospective randomized controlled study method was adopted, and the eligible patients were randomly divided into two groups in a ratio of 1 : 1 and treated with emergency LCBDE + LC and ERCP + LC, respectively. The relevant clinical data of the two groups were compared. RESULTS: The operation duration was longer and blood loss was greater in the LCBDE + LC group than in the ERCP + LC group, but the therapeutic cost was significantly lower in the former than in the latter. The differences were statistically significant (p < 0.05 in all). There was no severe complication in either group. The total number of cases with complications, incidence of postoperative acute pancreatitis and incidence of hemorrhage were higher in the ERCP + LC group than in the LCBDE + LC group, while the incidence of bile leakage was lower in the former than in the latter. The differences were statistically significant (p < 0.05 in all). CONCLUSIONS: Both protocols were safe and feasible in the management of grade I or II acute calculous cholangitis. Compared with the protocol of ERCP + LC, the protocol of LCBDE + LC had the advantages of fewer complications and lower therapeutic costs and is worthy of clinical promotion.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Identification of Prognosis-Related RNA-Binding Proteins to Reveal the Role of RNA-Binding Proteins in the Progression and Prognosis of Colon Cancer.

BACKGROUND: RNA binding proteins (RBPs) are now under discussion as novel promising bio-markers for patients with colon cancer. The purpose of our study is to identify several RBPs related to the progression and prognosis of colon cancer and to further investigate the mechanism of their influence on tumor progression. METHODS: The transcriptome data of colon cancer and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to elucidate the gene functions and relative pathways. Cox and Lasso regression analyses were used to analyze the effect of immune genes on the prognosis of colon cancer. An immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate Cox regression analysis was utilized to investigate whether the immune gene risk score model was an independent factor for predicting the prognosis of colon cancer. A nomogram was constructed to comprehensively predict the survival rate of colon cancer. P < 0.05 was considered statistically significant. RESULTS: The results showed that 473 RBPs exhibited differential expression between normal and colon cancer tissues (P < 0.05). Univariate Cox regression analysis revealed 25 RBPs statistically correlated with colon cancer-related survival risk (P < 0.05). In addition, a 10-RBPs based risk scoring model was constructed through multivariate Cox regression analysis. A K-M curve indicated that high-risk patients were associated with poor outcomes (P < 0.001). A ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year overall survival (OS), area under curve (AUC) = 0.782). Our model showed satisfying AUC and survival correlation in the validation dataset (5-year OS, AUC = 0.744). Furthermore, multivariate Cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer. Finally, we found that 10-RBPs and risk scores were significantly associated with clinical factors and prognosis and were involved in multiple oncogenic pathways. CONCLUSION: Collectively, RBPs play an essential role in the progression and prognosis of colon cancer by regulating multiple biological pathways. Furthermore, the RBP risk score was an independent predictive factor of colon cancer, indicating poor survival.

Exploring a New Adaptive Routing Based on the Dijkstra Algorithm in Optical Networks-on-Chip.

The photoelectric hybrid network has been proposed to achieve the ultrahigh bandwidth, lower delay, and less power consumption for chip multiprocessor (CMP) systems. However, a large number of optical elements used in optical networks-on-chip (ONoCs) generate high transmission loss which will influence network performance severely and increase power consumption. In this paper, the Dijkstra algorithm is adopted to realize adaptive routing with minimum transmission loss of link and reduce the output power of the link transmitter in mesh-based ONoCs. The numerical simulation results demonstrate that the transmission loss of a link in optimized power control based on the Dijkstra algorithm could be maximally reduced compared with traditional power control based on the dimensional routing algorithm. Additionally, it has a greater advantage in saving the average output power of optical transmitter compared to the adaptive power control in previous studies, while the network size expands. With the aid of simulation software OPNET, the network performance simulations in an optimized network revealed that the end-to-end (ETE) latency and throughput are not vastly reduced in regard to a traditional network. Hence, the optimized power control proposed in this paper can greatly reduce the power consumption of s network without having a big impact on network performance.

CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice.

Cardiac complications post-stroke are common, and diabetes exacerbates post-stroke cardiac injury. In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improves cardiac function in type 2 diabetes mellitus (T2DM) stroke mice. Adult (3-4 m), male, BKS.Cg-m+/+Leprdb/J (db/db, T2DM) and non-DM (db+) mice were randomized to sham or photothrombotic stroke groups. T2DM-stroke mice were treated with phosphate-buffered saline (PBS) or CD133+Exo (20 µg, i.v.) at 3 days after stroke. T2DM sham and T2DM+CD133+Exo treatment groups were included as controls. Echocardiography was performed, and mice were sacrificed at 28 days after stroke. Cardiomyocyte hypertrophy, myocardial capillary density, interstitial fibrosis, and inflammatory factor expression were measured in the heart. MicroRNA-126 expression and its target gene expression were measured in the heart. T2DM mice exhibit significant cardiac deficits such as decreased left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), increased left ventricular diastolic dimension (LVDD), and reduced heart rate compared to non-DM mice. Stroke in non-DM and T2DM mice significantly decreases LVEF compared to non-DM and T2DM-sham, respectively. Cardiac dysfunction is worse in T2DM-stroke mice compared to non-DM-stroke mice. CD133+Exo treatment of T2DM-stroke mice significantly improves cardiac function identified by increased LVEF and decreased LVDD compared to PBS treated T2DM-stroke mice. In addition, CD133+Exo treatment significantly decreases body weight and blood glucose but does not decrease lesion volume in T2DM-stroke mice. CD133+Exo treatment of T2DM mice significantly decreases body weight and blood glucose but does not improve cardiac function. CD133+Exo treatment in T2DM-stroke mice significantly decreases myocardial cross-sectional area, interstitial fibrosis, transforming growth factor beta (TGF-ß), numbers of M1 macrophages, and oxidative stress markers 4-HNE (4-hydroxynonenal) and NADPH oxidase 2 (NOX2) in heart tissue. CD133+Exo treatment increases myocardial capillary density in T2DM-stroke mice as well as upregulates endothelial cell capillary tube formation in vitro. MiR-126 is highly expressed in CD133+Exo compared to exosomes derived from endothelial cells. Compared to PBS treatment, CD133+Exo treatment significantly increases miR-126 expression in the heart and decreases its target gene expression such as Sprouty-related, EVH1 domain-containing protein 1 (Spred-1), vascular cell adhesion protein (VCAM), and monocyte chemoattractant protein 1 (MCP1) in the heart of T2DM-stroke mice. CD133+Exo treatment significantly improves cardiac function in T2DM-stroke mice. The cardio-protective effects of CD133+Exo in T2DM-stroke mice may be attributed at least in part to increasing miR-126 expression and decreasing its target protein expression in the heart, increased myocardial capillary density and decreased cardiac inflammatory factor expression.

Complete nucleotide sequence of a novel partitivirus infecting the plant-pathogenic fungus Phomopsis vexans.

Here, we report the molecular characterization of a novel partitivirus from Phomopsis vexans strain PvHZ002, a plant-pathogenic fungus infecting eggplant. The virus was designated "Phomopsis vexans partitivirus 1" (PvPV1). PvPV1 contains two dsRNA segments, dsRNA1 and dsRNA2, which are 1,662 bp and 1,628 bp long, respectively. Each segment contains a single open reading frame, putatively encoding RNA-dependent RNA polymerase (dsRNA 1) and capsid protein (dsRNA 2). A homology search and phylogenetic analysis showed that PvPV1 clustered with viruses of the genus Deltapartitivirus of the family Partitiviridae.

A Novel Algorithm for Routing Paths Selection in Mesh-Based Optical Networks-on-Chips.

Optical networks-on-chips (ONoCs) is an effective and extensible on-chip communication technology, which has the characteristics of high bandwidth, low consumption, and low delay. In the design process of ONoCs, power loss is an important factor for limiting the scalability of ONoCs. Additionally, the optical signal-to-noise ratio (OSNR) is an index to measure the quality of ONoCs. Nowadays, the routing algorithm commonly used in ONoCs is the dimension-order routing algorithm, but the routing paths selected by the algorithm have high power loss and crosstalk noise. In this paper, we propose a 5×5 all-pass optical router model for two-dimensional (2-D) mesh-based ONoCs. Based on the general optical router model and the calculation models of power loss and crosstalk noise, a novel algorithm is proposed in ordder to select the routing paths with the minimum power loss. At the same time, it can ensure that the routing paths have the approximately optimal OSNR. Finally, we employ the Cygnus optical router to verify the proposed routing algorithm. The results show that the algorithm can effectively reduce the power loss and improve the OSNR in the case of network sizes of 5×5 and 6×6. With the increase of the optical network scale, the algorithm can perform better in reducing the power loss and raising the OSNR.

High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial-mesenchymal transition in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a more frequent subtype of lung cancer and most cases are discovered in the late stages. The proliferation and metastasis of LUAD are pivotal for disease progression. Despite unremitting deeper understanding of LUAD biology, the mechanisms involved in the proliferation and metastasis of LUAD remain unclear. The objective of our article was to inquiry the expression and the function of keratin 6C (KRT6C) in LUAD cells. METHODS: First, the expression level and prognostic value of KRT6C in LUAD tissues were analyzed on the basis of the data acquired from TCGA database. Through qRT-PCR, the expression level of KRT6C on LUAD cell lines (A549, H1299, PC-9) and human normal lung cell line MRC-5 was tested. After that, CCK8 and colony formation assays was utilized to detect cell proliferation. In addition, to explore the influence of KRT6C on LUAD migration and invasion ability, scratch wound healing and transwell assays were utilized. Through western blotting, the protein expression levels of KRT6C, PCNA, E-cadherin, N-cadherin, Snail and Vimentin were detected. RESULTS: The outcomes revealed that KRT6C was highly expressed in LUAD tissues and cell lines. Besides, elevated level of KRT6C was related to worse prognosis in LUAD patients. Ablation of KRT6C restrained proliferation, migration and invasion of A549 cells. KRT6C deficiency augmented the expression of E-cadherin as well as reduced the expression of N-cadherin, Snail and Vimentin. CONCLUSION: Above all, these consequences indicated that depletion of KRT6C suppressed A549 cell proliferation, migration and invasion, which might be achieved by regulating EMT. In general, KRT6C is identified as a potential therapeutic target for LUAD.

N-acetyl-seryl-aspartyl-lysyl-proline treatment protects heart against excessive myocardial injury and heart failure in mice.

Myocardial infarction (MI) in mice results in cardiac rupture at 4-7 days after MI, whereas cardiac fibrosis and dysfunction occur later. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory, anti-fibrotic, and pro-angiogenic properties. We hypothesized that Ac-SDKP reduces cardiac rupture and adverse cardiac remodeling, and improves function by promoting angiogenesis and inhibiting detrimental reactive fibrosis and inflammation after MI. C57BL/6J mice were subjected to MI and treated with Ac-SDKP (1.6 mg/kg per day) for 1 or 5 weeks. We analyzed (1) intercellular adhesion molecule-1 (ICAM-1) expression; (2) inflammatory cell infiltration and angiogenesis; (3) gelatinolytic activity; (4) incidence of cardiac rupture; (5) p53, the endoplasmic reticulum stress marker CCAAT/enhancer binding protein homology protein (CHOP), and cardiomyocyte apoptosis; (6) sarcoplasmic reticulum Ca2+ ATPase (SERCA2) expression; (7) interstitial collagen fraction and capillary density; and (8) cardiac remodeling and function. Acutely, Ac-SDKP reduced cardiac rupture, decreased ICAM-1 expression and the number of infiltrating macrophages, decreased gelatinolytic activity, p53 expression, and myocyte apoptosis, but increased capillary density in the infarction border. Chronically, Ac-SDKP improved cardiac structures and function, reduced CHOP expression and interstitial collagen fraction, and preserved myocardium SERCA2 expression. Thus, Ac-SDKP decreased cardiac rupture, ameliorated adverse cardiac remodeling, and improved cardiac function after MI, likely through preserved SERCA2 expression and inhibition of endoplasmic reticulum stress.

[Effect of down-regulation of fatty acid synthase expression on proliferation, migration and invasion of bladder carcinoma UMUC3 cell lines].

OBJECTIVE: To investigate the effects of fatty acid synthase (FASN) on proliferation, migration and invasion of bladder cancer UMUC3 cell lines and possible mechanism. METHODS: The expression levels of FASN protein in 30 cases of bladder cancer and 15 cases of normal bladder tissues were detected by Immunohistochemistry. FASN siRNA and nonsense siRNA were transfected into UMUC3 cell lines by lipofectamine 2000 respectively, and the stable siFASN and siControl cell lines were successfully obtained after screening and identification for several times. The siFASN cell lines were set as the experimental group, while the siControl cell lines were set as the control group. The expressions of FASN protein and mRNA in the experimental group and the control group were detected by Western blot and real-time quantitative PCR (RT-PCR) respectively. Cell proliferation activities in two groups were detected by MTT assay and cell invasion and migration in two groups were detected by cell scratch test and Transwell invasive assays respectively. RESULTS: FASN protein was overexpressed in bladder cancer tissues, and it was closely correlated with pathological stage and grade (P＜0.05). Compared with the siControl group, the expressions of FASN mRNA and protein in the siFASN group cell lines were decreased significantly (P＜0.05). The cell proliferation ability, the migration ability and the number of transmembrane cells of siFASN group cell lines were reduced significantly (P＜0.05). CONCLUSION: The FASN overexpression may play an essential role in the development and progression of bladder cancer. Down-regulation of FASN expression can inhibit the proliferation, migration and invasion of bladder cancer cells, and inhibition of FASN expression is expected to be a new treatment for bladder cancer.

Regenerating infected bone defects with osteocompatible microspheres possessing antibacterial activity.

Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and -osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing. In the present study, bioresorbable porous-structured microspheres were fabricated from an amphiphilic block copolymer composed of poly(l-lactide) and poly(ethyl glycol) blocks. After being surface coated with mussel-inspired polydopamine, the microspheres were loaded with nanosilver via the reduction of silver nitrate and apatite via biomineralization in sequence. At optimized loading amounts, the nanosilver-loaded microspheres showed no unfavorable effects on the proliferation and differentiation of bone marrow mesenchymal stem cells despite preserving strong antibacterial activity in in vitro evaluations. For the critical-sized defects (φ = 8 mm) in the rat cranium that was pre-infected with Staphylococcus aureus, the filling of the dual-purpose microspheres demonstrated an effective way to kill bacteria in vivo, and in the meantime, it promoted new bone formation efficiently alongside the degradation of microspheres. Thus, the results suggested that bioresorbable microspheres with both osteoconductive and antibacterial activities were a good choice for treating infected bone defects.

Phosphorescent Modulation of Metallophilic Clusters and Recognition of Solvents through a Flexible Host-Guest Assembly: A Theoretical Investigation.

MP2 (Second order approximation of Møller⁻Plesset perturbation theory) and DFT/TD-DFT (Density functional theory/Time-dependent_density_functional_theory) investigations have been performed on metallophilic nanomaterials of host clusters [Au(NHC)2]⁺⋅⋅⋅[M(CN)2]-⋅⋅⋅[Au(NHC)2]⁺ (NHC = N-heterocyclic carbene, M = Au, Ag) with high phosphorescence. The phosphorescence quantum yield order of clusters in the experiments was evidenced by their order of µS1/ΔES1-T1 values ( µ S 1 : S0 → S1 transition dipole, ∆ E S 1 - T 1 : splitting energy between the lowest-lying singlet S1 and the triplet excited state T1 states). The systematic variation of the guest solvents (S1: CH3OH, S2: CH3CH2OH, S3: H2O) are employed not only to illuminate their effect on the metallophilic interaction and phosphorescence but also as the probes to investigate the recognized capacity of the hosts. The simulations revealed that the metallophilic interactions are mainly electrostatic and the guests can subtly modulate the geometries, especially metallophilic Au⋅⋅⋅M distances of the hosts through mutual hydrogen bond interactions. The phosphorescence spectra of hosts are predicted to be blue-shifted under polar solvent and the excitation from HOMO (highest occupied molecular orbital) to LUMO (lowest unoccupied molecular orbital) was found to be responsible for the ³MLCT (triplet metal-to-ligand charge transfer) characters in the hosts and host-guest complexes. The results of investigation can be introduced as the clues for the design of promising blue-emitting phosphorescent and functional materials.

PIAS-family proteins negatively regulate Glis3 transactivation function through SUMO modification in pancreatic ß cells.

Gli-similar 3 (Glis3) is Krüppel-like transcription factor associated with the transcriptional regulation of insulin. Mutations within the Glis3 locus have been implicated in a number of pathologies including diabetes mellitus and hypothyroidism. Despite its clinical significance, little is known about the proteins and posttranslational modifications that regulate Glis3 transcriptional activity. In this report, we demonstrate that the SUMO-pathway associated proteins, PIASy and Ubc9 are capable of regulating Glis3 transactivation function through a SUMO-dependent mechanism. We present evidence that SUMOylation of Glis3 by PIAS-family proteins occurs at two conserved lysine residues within the Glis3 N-terminus and modification of Glis3 by SUMO dramatically inhibited insulin transcription. Finally, we provide evidence that Glis3 SUMOylation increases under conditions of chronically elevated glucose and correlates with decreased insulin transcription. Collectively, these results indicate that SUMOylation may serve as a mechanism to regulate Glis3 activity in ß cells.

Overexpression of prostaglandin E2 EP4 receptor improves cardiac function after myocardial infarction.

BACKGROUND: Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types to elicit a variety of physiologic and pathophysiological effects. We recently reported that PGE2 via its EP3 receptor could reduce cardiac contractility of isolated myocytes and the working heart preparation. We thus hypothesized that there is an imbalance in the EP3/EP4 ratio towards EP3 in the failing heart and that overexpression of EP4 in a mouse model of heart failure would improve cardiac function. METHODS AND RESULTS: Our hypothesis was tested in a mouse model of myocardial infarction (MI) with the use of AAV9-EP4 driven by the myosin heavy chain promoter to overexpress EP4 in the cardiac myocytes. Echocardiography was performed to assess cardiac function. We found that overexpression of EP4 improved shortening fraction (p = 0.0025), ejection fraction (p = 0.0003), and reduced left ventricular dimension at systole (p = 0.0013). Overexpression of EP4 also significantly reduced indices of cardiac hypertrophy and interstitial collagen fraction. Animals treated with AAV9-EP4 also had a significant decrease in TNFα mRNA expression and in the number of macrophages and T cells migrated post MI coupled with a reduction in the expression of iNOS. CONCLUSION: Overexpression of EP4 improves cardiac function post MI. This may be mediated through reductions in adverse cardiac remodeling or via inhibition of cytokine/chemokine production.

Ac-SDKP decreases mortality and cardiac rupture after acute myocardial infarction.

The natural peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) decreases inflammation in chronic diseases such as hypertension and heart failure. However, Ac-SDKP effects on acute inflammatory responses during myocardial infarction (MI) are unknown. During the first 72 hours post-MI, neutrophils, M1 macrophages (pro-inflammatory), and M2 macrophages (pro-resolution) and release of myeloperoxidase (MPO) and matrix metalloproteinases (MMP) are involved in cardiac rupture. We hypothesized that in the acute stage of MI, Ac-SDKP decreases the incidence of cardiac rupture and mortality by preventing immune cell infiltration as well as by decreasing MPO and MMP expression. MI was induced by ligating the left descending coronary artery in C57BL/6 mice. Vehicle or Ac-SDKP (1.6 mg/kg/d) was infused via osmotic minipump. Cardiac immune cell infiltration was assessed by flow cytometry, cardiac MPO and MMP levels were measured at 24-48 hrs post-MI. Cardiac rupture and mortality incidence were determined at 7 days post-MI. In infarcted mice, Ac-SDKP significantly decreased cardiac rupture incidence from 51.0% (26 of 51 animals) to 27.3% (12 of 44) and mortality from 56.9% (29 of 51) to 31.8% (14 of 44). Ac-SDKP reduced M1 macrophages in cardiac tissue after MI, without affecting M2 macrophages and neutrophils. Ac-SDKP decreased MMP-9 activation in infarcted hearts with no changes on MPO expression. Ac-SDKP prevents cardiac rupture and decreases mortality post-acute MI. These protective effects of Ac-SDKP are associated with decreased pro-inflammatory M1 macrophage infiltration and MMP-9 activation.

Directing osteogenic differentiation of BMSCs by cell-secreted decellularized extracellular matrixes from different cell types.

Cell-secreted decellularized extracellular matrixes (D-ECM) are promising for conferring bioactivity and directing cell fate to facilitate tissue regeneration. A cell sheet is a good shape for obtaining D-ECM after decellularization. In this study, cell sheets derived from bone marrow mesenchymal stem cells (BMSCs), MC3T3 osteoblasts, and L929 fibroblasts were decellularized, the three types of D-ECMs obtained were investigated for their capabilities in inducing osteogenic differentiation of re-seeded BMSCs. The D-ECMs were found to be rich in collagen and glycosaminoglycan, at the same time, showing the presence of growth factors, such as vascular endothelial growth factor and bone morphogenetic protein. These all supported the proliferation of BMSCs well, however, they influenced the osteogenic differentiation of BMSCs to different extents. The D-ECM prepared from the BMSC sheet was found to promote the osteogenic differentiation of re-seeded BMSCs the most in vitro, as well as displaying the potential to induce ectopic osteogenesis when being subcutaneously implanted. The results suggested that D-ECMs would be promising for bone tissue engineering applications, however, they favored osteogenesis to different extents, which was closely related to the cell types.

High-Performance Li-Ion Capacitor Based on an Activated Carbon Cathode and Well-Dispersed Ultrafine TiO2 Nanoparticles Embedded in Mesoporous Carbon Nanofibers Anode.

A novel Li-ion capacitor based on an activated carbon cathode and a well-dispersed ultrafine TiO2 nanoparticles embedded in mesoporous carbon nanofibers (TiO2@PCNFs) anode was reported. A series of TiO2@PCNFs anode materials were prepared via a scalable electrospinning method followed by carbonization and a postetching method. The size of TiO2 nanoparticles and the mesoporous structure of the TiO2@PCNFs were tuned by varying amounts of tetraethyl orthosilicate (TEOS) to increase the energy density and power density of the LIC significantly. Such a subtle designed LIC displayed a high energy density of 67.4 Wh kg-1 at a power density of 75 W kg-1. Meanwhile, even when the power density was increased to 5 kW kg-1, the energy density can still maintain 27.5 Wh kg-1. Moreover, the LIC displayed a high capacitance retention of 80.5% after 10000 cycles at 10 A g-1. The outstanding electrochemical performance can be contributed to the synergistic effect of the well-dispersed ultrafine TiO2 nanoparticles, the abundant mesoporous structure, and the conductive carbon networks.