Incorporating Multivariate Auxiliary Information for Traffic Prediction on Highways.

Traffic flow prediction is one of the most important tasks of the Intelligent Transportation Systems (ITSs) for traffic management, and it is also a challenging task affected by many complex factors, such as weather and time. Many cities adopt efficient traffic prediction methods to control traffic congestion. However, most of the existing methods of traffic prediction focus on urban road scenarios, neglecting the complexity of multivariate auxiliary information in highways. Moreover, these methods have difficulty explaining the prediction results based only on the historical traffic flow sequence. To tackle these problems, we propose a novel traffic prediction model, namely Multi-variate and Multi-horizon prediction based on Long Short-Term Memory (MMLSTM). MMLSTM can effectively incorporate auxiliary information, such as weather and time, based on a strategy of multi-horizon time spans to improve the prediction performance. Specifically, we first exploit a multi-horizon bidirectional LSTM model for fusing the multivariate auxiliary information in different time spans. Then, we combine an attention mechanism and multi-layer perceptron to conduct the traffic prediction. Furthermore, we can use the information of multivariate (weather and time) to provide interpretability to manage the model. Comprehensive experiments are conducted on Hangst and Metr-la datasets, and MMLSTM achieves better performance than baselines on traffic prediction tasks.

Cloning and functional analysis of the novel rice blast resistance gene Pi65 in japonica rice.

KEY MESSAGE: Pi65, a leucine-rich repeat receptor-like kinase (LRR-RLK) domain cloned from Oryza sativa japonica, is a novel rice blast disease resistance gene. Rice blast seriously threatens rice production worldwide. Utilizing the rice blast resistance gene to breed rice blast-resistant varieties is one of the best ways to control rice blast disease. Using a map-based cloning strategy, we cloned a novel rice blast resistance gene, Pi65, from the resistant variety GangYu129 (abbreviated GY129, Oryza sativa japonica). Overexpression of Pi65 in the susceptible variety LiaoXing1 (abbreviated LX1, Oryza sativa japonica) enhanced rice blast resistance, while knockout of Pi65 in GY129 resulted in susceptibility to rice blast disease. Pi65 encodes two transmembrane domains, with 15 LRR domains and one serine/threonine protein kinase catalytic domain, conferring resistance to isolates of Magnaporthe oryzae (abbreviated M. oryzae) collected from Northeast China. There were sixteen amino acid differences between the Pi65 resistance and susceptible alleles. Compared with the Pi65-resistant allele, the susceptible allele exhibited one LRR domain deletion. Pi65 was constitutively expressed in whole plants, and it could be induced in the early stage of M. oryzae infection. Transcriptome analysis revealed that numerous genes associated with disease resistance were specifically upregulated in GY129 24 h post inoculation (HPI); in contrast, photosynthesis and carbohydrate metabolism-related genes were particularly downregulated at 24 HPI, demonstrating that disease resistance-associated genes were activated in GY129 (carrying Pi65) after rice blast fungal infection and that cellular basal metabolism and energy metabolism were inhibited simultaneously. Our study provides genetic resources for improving rice blast resistance and enriches the study of rice blast resistance mechanisms.

Identification of the hub susceptibility genes and related common transcription factors in the skeletal muscle of Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and its related complications contribute to the high morbidity and mortality in worldwide. Skeletal muscle insulin resistance plays a critical role in the onset of T2DM due to the decreasing in the insulin-stimulated glucose uptake. T2DM is associated not only with the inherited factors but also with the noninherited factors. However, the susceptibility genes related with the two factors and the transcription factors (TF) regulating the susceptibility genes in skeletal muscle, which aggravate the development of T2DM were still ill-defined. METHODS: In the present study, the expression profiles by the array of GSE25462 were retrieved from the GEO database. GEO2R was performed to validate the susceptibility differentially expressed genes (SDEG) in skeletal muscle of T2DM. Gene Ontology (GO) analysis and The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted via The Database for Annotation, Visualization, and Integrated Discovery (DAVID). A Protein-Protein Interaction (PPI) network was performed with the STRING. RESULTS: With the performance of GEO2R, 229 SDEGs in skeletal muscle of T2DM were identified. The biological processes (BP) of SDEGs was enriched in the cellular response to UV-B most significantly. KEGG pathway analysis revealed that the SDEGs were most significantly enriched in glycosaminoglycan degradation. 5 hub susceptibility genes (GPR84, CALCB, GCG, PTGDR, GNG8) in the skeletal muscle of T2DM were identified. Eventually, the common transcription factors regulating the hub susceptibility genes were identified by means of the online tool PROMO. CONCLUSIONS: Five hub susceptibility genes (GPR84, CALCB, GCG, PTGDR, GNG8) in the skeletal muscle of T2DM and the common transcription factors were identified. The outputs would provide new clues on the novel potential targets and the therapeutic strategies for treating T2DM and its related diseases.

The constricting effect of reduced coronary artery compliance on the left ventricle is an important cause of reduced diastolic function in patients with coronary heart disease.

BACKGROUND: Previous studies of left ventricular diastolic function (LVDF) have focused on the decrease in active and passive diastolic function due to ischemic factors but have not investigated if the decrease in compliance of the coronary arteries that bypass the surface of the heart and travel between the myocardium could cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis. METHODS AND RESULTS: 581 patients diagnosed with coronary heart disease (CHD) were divided into A group (patients are the control group), B group (patients with less than 50% coronary artery stenosis), C group (patients with coronary artery stenosis between 50 and 75%), D group (patients with coronary artery stenosis greater than 75%) according to the degree of coronary stenosis. The diastolic function of the ventricle is reflected by applying the relaxation time constant T value, which refers to the time between peak dp/dt and end-diastolic pressure in the left ventricle. It was concluded that there was a statistical difference in Gensini scores between patients in groups B, C and D (P < 0.001). And multiple linear regression analysis showed that T was correlated with Gensini score and C-dp/dtmax (R = 0.711, P < 0.001). Grouping according to the site of stent implantation and the number of stents implanted, it was found out that the changes in T values before and after left anterior descending artery (LAD) stent implantation were greater than left circumflex artery (LCX) and right coronary artery (RCA) (P < 0.001). And multiple linear regression revealed a correlation between T values and stent length, ventricular stiffness, and C-dp/dtmax (P = 0.001). CONCLUSIONS: The decrease in compliance of the coronary arteries bypassing the surface of the heart and travelling between the myocardium would cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis.

Impact of BMI on Long-Term Outcomes in Patients with ST-Segment Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention.

Aim: Obesity paradox remains a point of debate in ST-segment elevation myocardial infarction (STEMI) patients. The aim of this study was to examine the relationship between body mass index (BMI) and clinical outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods: Outcomes were assessed in 1429 STEMI patients undergoing PPCI between January 2009 and January 2010 in Beijing. Patients were classified into 6 groups according to age (the younger and elderly groups consisting of patients ≤65 and > 65 years old) and baseline BMI (normal weight, BMI < 24 kg/m2; overweight, 24 kg/m2 ≤BMI < 28 kg/m2; obese, BMI ≥ 28 kg/m2). The primary outcome was death, acute myocardial infarction (AMI), or revascularization. Results: On long-term follow-up (mean follow-up of 59 months), 13.9% of patients experienced the adverse event. Multivariate logistic regression analyses showed that low BMI was a significant predictor of the primary outcome only in the younger group. The odds ratio for overweight in comparison with normal weight was 0.741 (95% CI: 0.413-0.979; p = 0.038), the odds radio for obesity in comparison with normal-weight patients was 0.508 (95% CI: 0.344-0.750; p = 0.016) in the younger group. In the elderly group, diabetes, hypertension, triple disease, regular exercise, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARBs) use after discharge, and bleeding complication were associated with primary outcome. Conclusion: The obesity paradox was recognized only in the younger age group in STEMI patients undergoing PPCI.

Involvement of adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 in diallyl trisulfide-induced cytotoxicity in hepatocellular carcinoma cells.

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

Upregulation of ubiquitin-conjugating enzyme E2Z is associated with human hepatocellular carcinoma.

UBE2Z, a member of ubiquitin-conjugating enzymes, has been reported to participate in multiple biological processes. However, its roles in hepatocellular carcinoma (HCC) remain undiscovered. This study aimed at investigating the functions of UBE2Z in HCC. Firstly, we evaluated UBE2Z expression in HCC and identified associations among UBE2Z expression, clinicopathological features, copy number alterations, DNA methylation, and survival of patients using data from the Cancer Genome Atlas (TCGA). As a result, UBE2Z was remarkably overexpressed in HCC tissues relative to normal liver tissues (P < 0.05). High UBE2Z expression was significantly correlated with age, advanced TNM stage, histological grade, vascular invasion, elevated serum alpha-fetoprotein expression (AFP), worse overall survival (OS) and disease-free survival (DFS) of HCC patients (all P < 0.05). Besides, data mining in UCSC Xena Browser showed that UBE2Z DNA amplification which was significantly associated with its expression was common (108 out of 364) in HCC, and that the level of UBE2Z DNA methylation was negatively associated with its expression (Pearson's correlation = -0.4, P < 0.0001). After analyzing the datasets from TCGA, we further confirmed the up-regulation of UBE2Z in 60 HCC tissues and several HCC cell lines. Finally, functional assays were performed and showed that knockdown UBE2Z using small interfering RNA (siRNA) could significantly restrain tumor cell proliferation and suppress cell migration and cell invasion through repressing the expression of MMP2 and MMP9. Meanwhile, UBE2Z knockdown could effectively reduce the expression of p-ERK, p-p38, p-JNK, p-Stat3 and p-JAK2, suggesting that UBE2Z might promote HCC progression by targeting ERK and stat3 signaling pathway. These findings implied that UBE2Z might be considered as a prognostic biomarker in HCC and provided a potential therapeutic tumor-associated antigen for HCC.

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor.

Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action. Video abstract.

Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease.

OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs (single nucleotide polymorphisms), rs9486729 (SCML4 [Scm polycomb group protein-like 4]; odds ratio, 1.25; 95% CI, 1.17-1.34; P=3.51×10-11), rs17165136 (THSD7A [thrombospondin type 1 domain-containing 7A]; odds ratio 1.28; 95% CI, 1.21-1.35; P<1.00×10-25), and rs852787 (DAB1 [disabled-1]; odds ratio, 1.29; 95% CI, 1.21-1.38; P=2.02×10-14), associated with CAD with genome-wide significance. The risk allele of rs9486729 and protective allele of rs17165136 were associated with the decreased expression of their host genes, SCML4 and THSD7A, respectively, whereas rs852787 did not have transcriptional effects on any gene. Knockdown of SCML4 activated endothelial cells by increasing the expression of IL-6, E-selectin, and ICAM and weakened their antiapoptotic activity, whereas the knockdown of THSD7A had little effect on these endothelial cell functions but attenuated monocyte adhesion via decreasing the expression of ICAM, L-selectin, and ITGB2. We further showed that inhibiting the expression of SCML4 exacerbated endothelial dysfunction and vascular remodeling in a rat model with partial carotid ligation. CONCLUSIONS: We identify 3 novel loci associated with CAD and show that 2 genes, SCML4 and THSD7A, make functional contributions to atherosclerosis. How rs852787 and its host gene DAB1 are linked to CAD needs further studies.

Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: PARP1-binding protein (PARPBP/PARI/C12orf48), a negative regulator of homologous recombination (HR), has been suggested to function as an oncogene in cervical, lung, and pancreatic cancer. OBJECTIVE: To investigate the expression profile of PARPBP and its role in hepatocellular carcinoma (HCC). METHODS: Using data from the Cancer Genome Atlas and Human Protein Atlas databases, PARPBP expression level and its clinical implication in HCC were identified by t test and Chi-square test. The prognostic value of PARPBP in HCC was evaluated by Kaplan-Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) was used to screen biological pathways correlated with PARPBP expression in HCC. RESULTS: PARPBP was significantly upregulated in HCC tissues compared with normal liver tissues (P < 0.05). High PARPBP expression was significantly associated with elevated serum AFP level, vascular invasion, poor tumor differentiation, and advanced TNM stage (all P < 0.05). Kaplan-Meier analyses suggested that upregulation of PARPBP was correlated with worse overall survival (OS) and recurrence-free survival (RFS) in HCC. Multivariate analyses further confirmed that PARPBP upregulation was an independent indicator of poor OS and RFS (all P < 0.05). The prognostic nomograms based on PARPBP mRNA expression and TNM stage were superior to those based on the TNM staging system alone (all P < 0.05). Besides, PARPBP DNA copy gain and miR-139-5p downregulation were associated with PARPBP upregulation in HCC. GSEA revealed that "cell cycle," "HR," "DNA replication," and "p53 signaling" pathways were enriched in high PARPBP expression group. CONCLUSION: PARPBP may be a promising prognostic biomarker and candidate therapeutic target in HCC.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells.

Endothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

Thyroxine Affects Lipopolysaccharide-Induced Macrophage Differentiation and Myocardial Cell Apoptosis via the NF-κB p65 Pathway Both In Vitro and In Vivo.

BACKGROUND: Numerous studies have demonstrated that the inflammatory response is involved in the progression of lipopolysaccharide- (LPS-) induced myocardial cell apoptosis. Accumulating evidence has shown that thyroxine participates in diseases by downregulating the inflammatory response. This study aimed at investigating whether thyroxine alleviates LPS-induced myocardial cell apoptosis. METHODS: Bone marrow-derived macrophages (Mø) were treated with LPS and thyroxine, and Mø differentiation and Mø-related cytokine expression were measured. The effect of Mø differentiation on mouse cardiomyocyte (MCM) apoptosis was also detected in vitro. In addition, C57BL/6 mice underwent thyroidectomy and were treated with LPS 35 days later; subsequently, Mø differentiation and myocardial cell apoptosis in hearts were analyzed. To determine whether the nuclear factor-kappa B (NF-κB) p65 pathway mediates the effect of thyroxine on Mø differentiation and myocardial cell apoptosis, the specific NF-κB p65 pathway inhibitor JSH-23 was administered to mice that underwent a thyroidectomy. RESULTS: Levothyroxine treatment significantly reduced the activation of the NF-κB p65 pathway, decreased M1 macrophage (Mø1) differentiation and Mø1-related cytokine mRNA levels in LPS-treated Mø, and increased M2 macrophage (Mø2) differentiation and Mø2-related cytokine mRNA expression. The protective effects of levothyroxine on MCM apoptosis mediated by LPS-treated Mø were alleviated by JSH-23. In mice, thyroidectomy aggravated LPS-induced cardiac injury and cardiac dysfunction, further promoted NF-κB p65 activation, and increased cardiac Mø1 expression and myocardial cell apoptosis but decreased cardiac Mø2 expression. JSH-23 treatment significantly ameliorated the thyroidectomy-induced increases in myocardial cell apoptosis and Mø differentiation. CONCLUSIONS: Thyroxine alleviated the Mø1/Mø2 imbalance, reduced the inflammatory response, decreased myocardial cell apoptosis, and protected against cardiac injury and cardiac dysfunction in LPS-treated mice. Thyroxine may be a novel therapeutic strategy to prevent and treat LPS-induced cardiac injury.

[Investigation and application of Dendrobium resources in Qinba Mountains with a discussion on industrial poverty alleviation model].

The Dendrobium species are rare and endangered medicinal plants, and it is difficult to investigate their wild resources with conventional methods because of typical epiphytic herbaceous. We explored Dendrobium resources(include culture resource) of Qinba Mountains and the boundary Mountain area in Hubei, Chongqing using the methods of literatures and field investigation, and found that the cultural base of Dendrobium were profound in Qinba Mountains region. Furthermore, its germplasm resources of Dendrobium were established for the first time in Wanzhou Luotian town. In case the advantages of local rock resources and poverty alleviation demand, we have actively carried out the cultivating mode of Dendrobium which grow on rock, and the poverty alleviation model of local characteristic Dendrobium industry were established preliminarily. Our application case can provide reference for the mining and transformation of traditional Chinese medicine resources census results.

Monocarboxylate transporters in breast cancer and adipose tissue are novel biomarkers and potential therapeutic targets.

Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumours including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients. Our study found that MCT1 overexpression was observed in hormone receptor-negative and high-proliferation subtypes. High expression of MCT1 and MCT4 in tumour tissues was associated with poor patient outcome; further the correlation between MCT1 expression and poor prognosis in breast cancer was further strengthened when combined with MCT4 overexpression in the adjacent adipose tissue. These results demonstrate that MCTs tend to play a role in the aggressive BC subtypes through the dynamic interaction between breast cancer cells and adipocytes, and developing therapeutics to block this interaction will be a promising strategy in cancer therapy.

[Analysis on ecological factors and active components content of wild Dipsacus asper in Chongqing Wulong district].

An HPLC method was developed for the determination of iridoid glycosides (loganin acid, loganin, sweroside) and saponins (asperosaponin Ⅵ) in the wild Dipsacus asper. A total of 108 samples consecutive growing 12 month were collected in 9 plots in Wulong district of Chongqing. Subsequent analysis of the content of loganin acid, loganin, sweroside and asperosaponin Ⅵ was performed by HPLC to evaluate the quality. In addition, 20 climate data provided by the world climate database (http://www.worldclim.org/) was analyzed to deduce the correlation between the growing environment factors and the active ingredient content accumulation of D. asperoides and choose the apposite growing environment for D. asper. The range of active ingredient content in wild D. asper were 0.01%-3.80%(loganin acid), 0.08%-0.62%(loganin), 0.12%-0.78%(sweroside), 0.64%-5.26%(asperosaponin Ⅵ). The highest content of these active ingredients was concentrated from February to April, with 2.64% of loganin acid, 0.36% of loganin), 0.57% of sweroside, and 3.09% of asperosaponin Ⅵ. The method used for determination of the active ingredient content in D. asper was simple and convenient with accurate result. The selection of the quadrats is scientific and reasonable and can be used for the analysis of the contents of the wild D. asper, thus provide a reference for quality evaluation of D. asper and protection of D. asper resources.

[Textual research on origin and genuine of Lilii Bulbus].

Lilii Bulbus, which comes from many medicinal plants，is a frequently-used traditional Chinese medicine，the records in previous herbal literatures of it's origin and quality were inconstant. To trace back it's sources, we conducted a systematical study on it's origin and quality by textual research and investigation in this paper,The result showed that the origins of Lilii Bulbus are mainly source from white-flowers, red-yellow-flowers and red-flowers of Lilium， L. brownii var. viridulum, which were believed authentic or good quality in all previous herbal literatures,and L. pumilum and L. concolor which belong to white-flowers,and L. lancifolium which belong to red-yellow-flowers were believed low-quality and unfit for medicinal uses, or they were listed below and often have different effect with L. brownii var. viridulum. Among them, only L. concolor does not belong to Lilii Bulbus according to Chinese Pharmacopeia (2015 edition), The mainstream varieties of Lilii Bulbus became L. lancifolium now according to our practical investigation, which were very different from previous herbal literatures. Although chemical and pharmacological studies provided a reference for L. lancifolium，we should respect the actual records of the previous herbal literatures，the research of material foundation of efficacy should be more sufficient，and provide science evidence for clinical application of different species of Lilii Bulbus.

High-contrast wide-field evanescent wave illuminated subdiffraction imaging.

In this Letter, we show how to obtain high-contrast wide-field evanescent wave illuminated subdiffraction imaging through controlling nanoscale light-matter interaction. The light coupling, propagation, and far-field imaging processes show strong polarization selectivity and film quality dependence, which is used to improve the image-contrast-to-noise ratio (CNR) and to enlarge the field of view (FOV). We demonstrate experimentally high CNR subdiffraction imaging with lateral resolution of 122 nm and FOV of thousands of micrometers square.

Tiron ameliorates high glucose-induced cardiac myocyte apoptosis by PKCδ-dependent inhibition of osteopontin.

Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)-induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill-defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)-treated NRVMs and the left ventricular cardiomyocytes from STZ-diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG-induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG-stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS-mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis-related cardiovascular diseases including diabetic cardiomyopathy.

Wogonin enhances intracellular adiponectin levels and suppresses adiponectin secretion in 3T3-L1 adipocytes.

As an insulin sensitizer and modulator of inflammatory responses, adiponectin has become a therapeutic target for insulin resistance, diabetes, and diabetes-related complications. Wogonin possesses anti-oxidative, anti-inflammatory, and anti-diabetic abilities. However, its effect on generation and secretion of adiponectin is ill-defined in adipocytes. Here, we demonstrated that wogonin administration augmented intracellular adiponectin levels and attenuated adiponectin release in a dose- and time-dependent manner in mature 3T3-L1 adipocytes, along with a suppression of PKCδ phosphorylation. Wogonin treatment also prevented PKCδ overexpression-induced reduction of intracellular adiponectin levels and enhancement of adiponectin release. In addition, wogonin supplementation dramatically increased AMPK phosphorylation and SirT1 expression. Inhibition of either AMPK or SirT1 mitigated wogonin action on adiponectin production and release. Furthermore, inhibition of AMPK by its specific inhibitor markedly reduced wogonin-enhanced mRNA and protein expressions of SirT1. These results suggested that wogonin regulated expression and secretion of adiponectin via PKCδ/AMPK/SirT1 signaling pathway in mature 3T3-L1 adipocytes.