Detection of Pyrophosphate and Alkaline Phosphatase Activity Based on PolyT Single Stranded DNA - Copper Nanoclusters.

The determination of pyrophosphate and alkaline phosphatase activity plays a significant role in medical diagnosis. In this work, a label-free "ON-OFF-ON" fluorescence strategy is developed for the analysis of pyrophosphate and alkaline phosphatase activity. Using PolyT single strand DNA as templates to synthesize fluorescent copper nanoparticles, the coordination effect of pyrophosphoric acid on Cu2+ inhibited the generation of fluorescence. Afterwards, the addition of alkaline phosphatase into hydrolyze pyrophosphoric acid resulted in the release of Cu2+, whereby the fluorescence intensity could be recovered. Thereupon enhanced-sensitivity for alkaline phosphatase was obtained (0.1 mU/L), much better than previously reported methods. Meanwhile, it could be performed directly in homogeneous solution, which was very close to the actual activity level of alkaline phosphatase under physiological conditions. Likewise, satisfactory results were also obtained in specificity assessment, which demonstrated its potential application in clinical diagnosis. Notably, a new, sensitive, low-cost, short-time, and high-sensitivity platform for alkaline phosphatase detection was constructed, and the design of biosensor using DNA-templated Copper nanoclusters (CuNCs) was instructed in this study.

A Sensitive Fluorescent Assay for Tetracycline Detection Based on Triple-helix Aptamer Probe and Cyclodextrin Supramolecular Inclusion.

Herein, an effective pyrene excimer signaled fluorescent biosensor for the determination of tetracycline based on triple-helix aptamer probe (TAP) and supramolecular inclusion of cyclodextrin was reported. The TAP was devised containing an aptamer loop, two DNA segment stems and a triplex-forming oligonucleotide (signal probe) labeled with pyrenes at 5' and 3' ends. The presence of target could result in its binding towards aptamer with a mighty affinity, leading to a conformation change of the TAP and whereupon the release of the signal probe. This liberty of signal probe enabled the formation of pyrene excimer, generating fluorescence signals. Further, signal amplification was fulfilled through the addition of γ-cyclodextrin which could interact with pyrene dimer, thus leading to an enhanced "on-state" of the sensing ensemble. In contrast, when the target was absent, the sensing ensemble remained "off-state" because of the long distance between two pyrene molecules. When the conditions were properly optimized, the increasing signal kept a linear dependence on target concentrations ranging from 5.0 nM to 100 nM, and the detection limit reached as low as 1.6 nM. In this way, a newly-constructed, simple, and economically affordable protocol enjoys desirable efficiency, sensitivity, specificity in biosensing. Also, its universality as another attractive behalf in assaying diverse targets was envisioned with only the need of matched aptamer replacement.

[Effect of shear stress on eicosanoid metabolism in endothelial cells by metabolomics approach].

The article aims to study the effect and mechanism of shear stress on eicosanoids produced by the metabolism of polyunsaturated fatty acids in endothelial cells. First, human umbilical vein endothelial cells were treated by control (Static), laminar shear stress (LSS) and oscillatory shear stress (OSS) for 6 h. Then the endothelial cells were incubated with fresh M199 medium for 3 h, and the cell culture medium was collected. Ultra-performance liquid chromatography-mass spectrometer was used to detect the level of eicosanoid metabolites secreted by endothelial cells. The results showed that under different shear stress, the level of eicosanoid metabolites were changed significantly. We found 10 metabolites were significantly up-regulated by OSS compared with those in LSS group, including PGD2, PGE2, PGF2α and PGJ2 produced by cyclooxygenase; 11-HETE, 15-HETE, 13-HDoHE produced by lipoxygenase or spontaneous oxidation; 12,13-EpOME, 9,10-EpOME, 9,10-DiHOME produced by cytochrome P450 oxidase and soluble epoxide hydrolase. The transcription levels of these up-regulated eicosanoids metabolic enzyme-related genes were also increased in vitro and in vivo. These results indicate that OSS may promote the increase of metabolites by up-regulating the transcription level of metabolic enzyme-related genes, which playing a key role in the development of atherosclerosis. This study reveals the effect of shear stress on eicosanoid metabolism in endothelial cells, which provides a novel supplement to the systems biology approach to study systemic hemodynamics.

[n-3 Polyunsaturated fatty acid attenuates hyperhomocysteinemia-induced hepatic steatosis by increasing hepatic LXA5 content].

Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are major health problems worldwide, whose incidence are closely related with each other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels were measured by ELISA to confirm the establishment of an HHcy model. Meantime, mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results showed that n-3 PUFA significantly improved hepatic lipid deposition induced by HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition of hepatic Cd36 expression was associated with the inactivation of aryl hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry revealed that hepatic content of lipoxin A5 (LXA5) was significantly increased in HMD+n-3 PUFA-fed mice compared with that in HMD-fed mice. In primary cultured hepatocytes, LXA5 treatment markedly reversed homocysteine-evoked Cd36 upregulation and Ahr activation, which resulted in reduced lipid accumulation. In conclusion, we demonstrate that n-3 PUFA inactivates HHcy-induced Ahr-Cd36 pathway by increasing hepatic LXA5 content, which alleviates hepatic steatosis. Thus, our results may provide a potential strategy for treatment of NAFLD.

Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells.

RATIONALE: Angiogenesis is a complex process regulating endothelial cell (EC) functions. Emerging lines of evidence support that YAP (Yes-associated protein) plays an important role in regulating the angiogenic activity of ECs. OBJECTIVE: The objective of this study was to specify the effect of EC YAP on angiogenesis and its underlying mechanisms. METHOD AND RESULTS: In ECs, vascular endothelial growth factor reduced YAP phosphorylation time and dose dependently and increased its nuclear accumulation. Using Tie2Cre-mediated YAP transgenic mice, we found that YAP promoted angiogenesis in the postnatal retina and tumor tissues. Mass spectrometry revealed signal transducer and activator of transcription 3 (STAT3) as a potential binding partner of YAP in ECs. Western blot and immunoprecipitation assays indicated that binding with YAP prolonged interleukin 6-induced STAT3 nuclear accumulation by blocking chromosomal maintenance 1-mediated STAT3 nuclear export without affecting its phosphorylation. Moreover, angiopoietin-2 expression induced by STAT3 was enhanced by YAP overexpression in ECs. Finally, a selective STAT3 inhibitor or angiopoietin-2 blockage partly attenuated retinal angiogenesis in Tie2Cre-mediated YAP transgenic mice. CONCLUSIONS: YAP binding sustained STAT3 in the nucleus to enhance the latter's transcriptional activity and promote angiogenesis via regulation of angiopoietin-2.

[Research progress on genus Clinopodium].

The plants of genus Clinopodium are perennial herbs of Labiatae, which are widely distributed in the world and have a promising medicinal value. Modern researches have shown flavonoids, triterpenoid saponins, terpene glycosides, terpenoids, volatile oils and phenylpropanoids are the main compounds in the plants, presenting various pharmacological effects such as hemostasis, anti-bacteria, anti-inflammation, immunoregulation, reducing blood glucose, antioxidation, and anti-tumor effects. The preparations made of those plants are mainly used for treatment of various bleeding diseases in clinical application. In this review, we systematically summarized the research progress on taxonomy, resource distribution, chemical compositions, pharmacological activities, and clinical application of the medicinal plants of genus Clinopodium. This review provides references and scientific basis for further research and development of genus Clinopodium.

Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing ß-oxidation of fatty acid in mice.

Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg·kg-1·day-1 for the animal model and 1 µM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-α (PPAR-α), as evidenced by elevated ß-oxidation of fatty acids and the expression of PPAR-α target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-α activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-α. Of note, 11,12-EET ligand dependently activated PPAR-α. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-α was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.

Promoting Ethics and Integrity in Management Academic Research: Retraction Initiative.

In the management academic research, academic advancement, job security, and the securing of research funds at one's university are judged mainly by one's output of publications in high impact journals. With bogus resumes filled with published journal articles, universities and other allied institutions are keen to recruit or sustain the appointment of such academics. This often places undue pressure on aspiring academics and on those already recruited to engage in research misconduct which often leads to research integrity. This structured review focuses on the ethics and integrity of management research through an analysis of retracted articles published from 2005 to 2016. The study employs a structured literature review methodology whereby retracted articles published between 2005 and 2016 in the field of management science were found using Crossref and Google Scholar. The searched articles were then streamlined by selecting articles based on their relevance and content in accordance with the inclusion criteria. Based on the analysed retracted articles, the study shows evidence of ethical misconduct among researchers of management science. Such misconduct includes data falsification, the duplication of submitted articles, plagiarism, data irregularity and incomplete citation practices. Interestingly, the analysed results indicate that the field of knowledge management includes the highest number of retracted articles, with plagiarism constituting the most significant ethical issue. Furthermore, the findings of this study show that ethical misconduct is not restricted to a particular geographic location; it occurs in numerous countries. In turn, avenues of further study on research misconduct in management research are proposed.

Membranous subaortic stenosis coexisting with hypertrophic cardiomyopathy: A case report.

Subaortic stenosis (SAS) is a congenital heart disease, and its association with hypertrophic cardiomyopathy is very rare and clinically underappreciated. We report here a case of a 45-year-old female who was admitted to our hospital with chest tightness and shortness of breath. Both transthoracic and transesophageal echocardiography revealed asymmetric left ventricular hypertrophy and a membrane-like echo below the level of the aortic valve. This patient was diagnosed with membranous SAS with hypertrophic cardiomyopathy. Screening of her immediate family members revealed that her son also had hypertrophic cardiomyopathy. The patient chose conservative treatments and has been closely followed-up after discharge.

Effect of carboprost tromethamine in prevention of postpartum hemorrhage in cesarean section.

Carboprost tromethamine is a synthetic prostaglandin derivative, which can effectively promote law contraction of the uterus and significantly reduce the amount of bleeding during and after delivery. In this study, we explored the effect of carboprost tromethamine on the prevention of postpartum hemorrhage after cesarean section and the effect on coagulation function and hemodynamics. At the same time, the effects of oxytocin and carboprost tromethamine were studied in different groups. The results showed that the amount of 2h bleeding (256.7±65.21) mL and the amount of 24h hemorrhage (308.3±78.3) after the operation were significantly decreased, and the difference was statistically significant (P<0.05). After the operation, the levels of APTT, TT and Fib in the two groups were significantly lower than those before the operation. The levels of SBP (119.4±8.24) mmHg and DBP (79.6±6.21) mmHg in the experimental group were significantly higher than those of the control group. In summary, carboprost tromethamine has a significant effect on the prevention of postpartum hemorrhage in cesarean section, and has a significant effect on improving the state of hypercoagulable blood and maintaining the stable hemodynamic state, which has clinical a value.

Hyperhomocysteinemia activates the aryl hydrocarbon receptor/CD36 pathway to promote hepatic steatosis in mice.

UNLABELLED: Hyperhomocysteinemia (HHcy) is associated with liver diseases such as fatty liver and hepatic fibrosis; however, the underlying mechanism is still largely unknown. The current study aimed to explore the signaling pathway involved in HHcy-induced hepatic steatosis (HS). C57BL/6 mice were fed a high-methionine diet (HMD) for 4 and 8 weeks to establish the HHcy mouse model. Compared to a chow diet, the HMD induced hepatic steatosis and elevated hepatic expression of CD36, a fatty acid transport protein. The increased CD36 expression was associated with activation of the aryl hydrocarbon receptor (AHR). In primary cultured hepatocytes, high levels of homocysteine (Hcy) treatment up-regulated CD36 and increased subsequent lipid uptake; both were significantly attenuated by small interfering RNA (siRNA) knockdown of CD36 and AHR. Chromatin immunoprecipitation assay revealed that Hcy promoted binding of AHR to the CD36 promoter, and transient transfection assay demonstrated markedly increased activity of the AHR response element by Hcy, which was ligand dependent. Mass spectrometry revealed significantly increased hepatic content of lipoxin A4 (LXA4 ), a metabolite of arachidonic acid, in HMD-fed mice. Furthermore, overexpression of 15-oxoprostaglandin 13-reductase 1, a LXA4 inactivation enzyme, inhibited Hcy-induced AHR activation, lipid uptake, and lipid accumulation. Moreover, LXA4 -induced up-regulation of CD36 and lipid uptake was inhibited by AHR siRNA in vitro in hepatocytes. Finally, treatment with an AHR antagonist reversed HHcy-induced lipid accumulation by inhibiting the AHR-CD36 pathway in mice. CONCLUSION: HHcy activates the AHR-CD36 pathway by increasing hepatic LXA4 content, which results in hepatic steatosis. (Hepatology 2016;64:92-105).

Unethical Admissions: Academic Integrity in Question.

The increasing unethical practices of graduates' admissions have heightened concerns about the integrity of the academy. This article informs this important subject that affects the students, admission systems, and the entire scientific community, thus, representing an approach against scholarly black market activities including falsified documents and unethical practices by consultants and students' recruitment agencies.

Highly selective separation of tetravalent plutonium from complex system with novel phenylpyridine diamide ligands.

In this study, three phenylpyridine diamide ligands, namely, 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis(N,N-diethylacetamide) (PPEA, L1), 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis(N-ethyl-N-phenylacetamide) (PEPA, L2), and 2,2'-(((4-phenylpyridine-2,6-diyl)bis(3,1-phenylene))bis(oxy))bis(N,N-dioctylacetamide) (PPOA, L3), were synthesized and explored for the solvent extraction of Pu(iv) in a HNO3 medium using 1-(trifluoromethyl)-3-nitrobenzene as the diluent. The effects of HNO3 concentration, extractant concentration, and temperature on the Pu(iv) extraction efficiency were studied. All three extractants displayed high selectivity for Pu(iv) over other metals such as U(vi), Np(v), Am(iii), and various fission elements. At 3 M HNO3, the distribution ratio for Pu(iv) reached 27.18, in contrast to 1.11, 0.3, and 0.03 for U(vi), Np(v), Am(iii), respectively. Slope analysis and UV titration revealed the formation of 1 : 1 Pu(NO3)4/ligand complexes during extraction. The extraction reactions had negative Gibbs free energies, indicating the spontaneous nature of Pu(iv) extraction at room temperature. Furthermore, the extractants demonstrated good stripping ability and reusability, and their radiolytic stability was reasonable up to an absorbed dose of 100 kGy, underscoring their potential for practical applications. Overall, this study broadens our understanding of actinide-diamide ligand coordination and actinide chemistry during coordination, paving the way for the design and synthesis of new extractants.

Bufotalin attenuates pulmonary fibrosis via inhibiting Akt/GSK-3ß/ß-catenin signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented ß-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-ß1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3ß Ser9 (p-GSK-3ß S9), thereby reactivating GSK-3ß. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3ß/ß-catenin axis downstream of TGF-ß1. Thus, BT could be a potential option to be further explored in IPF treatment.

[Research on the compatibility laws in treating rheumatoid arthritis patients of cold-dampness obstruction syndrome].

OBJECTIVE: To find out Chinese herbal compounds (CHCs) with high frequency in treating rheumatoid arthritis (RA) patients of cold-dampness obstruction syndrome (CDOS) by inductively reviewing literatures concerning clinical application of CHCs, thus improving theoretical and medical practice levels of Chinese medical recipes. METHODS: The CHCs for treating RA patients of CDOS published in medical journals in recent 30 years were retrieved. The database of CHCs was set up. The herbal functions, meridian tropism, flavors and properties were statistically analyzed. RESULTS: There were 126 single herbs in CHCs for treating RA patients of CDOS. The top 31 single herbs occupied 70.7% cumulative frequency, being high frequency CHCs for treating RA patients of CDOS. From the function aspect, the anti-rheumatic herbs, asthenia supplementing herbs, diaphoretic, and herbs for activating blood circulation and removing blood stasis were identified as high frequency CHCs. From the meridian tropism aspect, Gan-meridian, Pi-meridian and Shen-meridian, occupied the top 3. As for flavors, acid, bitter, and sweet occupied the top three. As for drug nature, herbs of warm property were used most frequently. CONCLUSION: The high frequency CHCs obtained from analytical statistics could provide evidence for clinical medication.

How Green Mindfulness and Green Shared Vision Interact to Influence Green Creative Behavior.

Aim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers' green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably. Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach's alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics. Results: Our findings indicate that green mindfulness significantly improves frontline managers' green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision. Discussion: To the best of the authors' knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.

Specific Overexpression of YAP in Vascular Smooth Muscle Attenuated Abdominal Aortic Aneurysm Formation by Activating Elastic Fiber Assembly via LTBP4.

Abdominal aortic aneurysm (AAA) is a fatal vascular disease. Vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AAA. Increasing evidence has shown that Yes-associated protein (YAP) is involved in diverse vascular diseases. However, the role of YAP in AAA remains unclear. The current study aimed to determine the role of YAP in AAA formation and the underlying mechanism. We found that YAP expression in VSMCs was markedly decreased in human and experimental AAA samples. Furthermore, VSMC-specific YAP overexpression prevented several pathogenic factor-induced AAA. Mechanistically, YAP overexpression in VSMCs promoted latent transforming growth factor-ß binding protein 4 (LTBP4) expression, an important factor in elastic fiber assembly. Finally, silencing of LTBP4 in VSMCs abolished the protective role of YAP in AAA formation in vivo. Our results suggest that YAP promotes LTBP4-mediated elastic fibril assembly in VSMCs, which mitigates elastin degradation and AAA formation.

Metabolic changes of glycerophospholipids during the reparative phase after myocardial infarction injury.

Introduction: Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, and its underlying mechanism is still largely unknown. Lipid levels and composition alterations predict the risk of MI complications. Glycerophospholipids (GPLs) are important bioactive lipids and play a crucial role in the development of cardiovascular diseases. However, the metabolic changes in the GPLs profile during post-MI injury remain unknown. Methods: In the current study, we constructed a classic MI model by ligating the left anterior descending branch and assessed the alterations in both plasma and myocardial GPLs profiles during the reparative phase post-MI by liquid chromatography-tandem mass spectrometry analysis. Results: We found that myocardial GPLs, but not plasma GPLs, were markedly changed after MI injury. Importantly, MI injury is associated with decreased phosphatidylserine (PS) levels. Consistently, the expression of phosphatidylserine synthase 1 (PSS1), which catalyzes the formation of PS from its substrate phosphatidylcholine, was significantly reduced in heart tissues after MI injury. Furthermore, oxygen-glucose deprivation (OGD) inhibited PSS1 expression and reduced PS levels in primary neonatal rat cardiomyocytes, while overexpression of PSS1 restored the inhibition of PSS1 and the reduction in PS levels caused by OGD. Moreover, overexpression of PSS1 abrogated, whereas knockdown of PSS1 aggravated, OGD-induced cardiomyocyte apoptosis. Conclusions: Our findings revealed that GPLs metabolism was involved in the reparative phase post-MI, and cardiac decreased PS levels, resulting from inhibition of PSS1, are important contributor to the reparative phase post-MI. PSS1 overexpression represents a promising therapeutic strategy to attenuate MI injury.

Prognostic value of admission heart rate in patients with ST-segment elevation myocardial infarction: role of type 2 diabetes mellitus.

BACKGROUND: It's unknown whether the prognostic value of admission heart rate (HR) was different in patients with ST-segment elevation myocardial infarction (STEMI) with or without concomitant type 2 diabetes mellitus (T2DM). METHODS: Consecutive STEMI patients who presented within 12 hours of symptom onset were recruited from 274 hospitals in China. Participants were stratified into quartiles by admission HR. Baseline characteristics, current therapeutic recommenda- tions, laboratory biochemical tests, 30-day all-cause mortality and Cardiovascular Events (CVE, including all-cause death, reinfarction and stroke) were compared across admission HR quartiles. RESULTS: We evaluated 7294 STEMI patients, of these 820 (11.2%) had known T2DM. The admission HR quartile stratification was significantly associated with all-cause mortality and CVE regardless of T2DM status (P < 0.001 both for survival and CVE). After adjusted other risk factors, in patients without T2DM, comparing with HR <66 b.p.m., the increase of HR level was associated with worse prognosis (P < 0.05). In patients with T2DM, the hazard ratios for 30-day CVE were 1.75 (95%CI), 1.92 (95%CI), 3.00 (95%CI) in the HR of 66-76 b.p.m., 77-88 b.p.m., and >88 b.p.m., respectively. Results were similar for 30-day all-cause mortality, but the hazard ratios in Q2 (P = 0.139 and P =0.086 for survival and CVE, respectively) and Q3 groups were non-significant (P = 0.072 and P =0.033 for survival and CVE, respectively). There was a significant interaction effect of HR and T2DM on 30-day CVE mortality (P = 0.035), which was not found on all-cause mortality (P = 0.126). CONCLUSION: Admission heart rate was an important risk factor of 30-day all-cause mortality and CVE in patients with STEMI with or without T2DM. However, the predictive effect was modified by T2DM.

The role of the Hippo pathway in heart disease.

Heart disease, including coronary artery disease, myocardial infarction, heart failure, cardiac hypertrophy, and cardiomyopathies, is the leading causes of death worldwide. The Hippo pathway is a central controller for organ size and tissue growth, which plays a pivotal role in determining cardiomyocytes and nonmyocytes proliferation, regeneration, differentiation, and apoptosis. In this review, we summarize the effects of the Hippo pathway on heart disease and propose potential intervention targets. Especially, we discuss the molecular mechanisms of the Hippo pathway involved in maintaining cardiac homeostasis by regulating cardiomyocytes and nonmyocytes function in the heart. Based on this, we conclude that the Hippo pathway is a promising therapeutic target for cardiovascular therapy, which will bring new perspectives for their treatments.