Giant elastocaloric effect at low temperatures in TmVO4 and implications for cryogenic cooling.

Adiabatic decompression of paraquadrupolar materials has significant potential as a cryogenic cooling technology. We focus on TmVO[Formula: see text], an archetypal material that undergoes a continuous phase transition to a ferroquadrupole-ordered state at 2.15 K. Above the phase transition, each Tm ion contributes an entropy of [Formula: see text] due to the degeneracy of the crystal electric field groundstate. Owing to the large magnetoelastic coupling, which is a prerequisite for a material to undergo a phase transition via the cooperative Jahn-Teller effect, this level splitting, and hence the entropy, can be readily tuned by externally induced strain. Using a dynamic technique in which the strain is rapidly oscillated, we measure the adiabatic elastocaloric response of single-crystal TmVO[Formula: see text], and thus experimentally obtain the entropy landscape as a function of strain and temperature. The measurement confirms the suitability of this class of materials for cryogenic cooling applications and provides insight into the dynamic quadrupole strain susceptibility.

Novel potential urinary biomarkers for effective diagnosis and prognostic evaluation of high-grade bladder cancer.

Background: High-grade bladder cancer (HGBC) has a higher malignant potential, recurrence and progression rate compared to low-grade phenotype. Its early symptoms are often vague, making non-invasive diagnosis using urinary biomarkers a promising approach. Methods: The gene expression data from urine samples of patients with HGBC was extracted from the GSE68020 dataset. The clinical information and gene expression data in tumor tissues of HGBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Multivariate Cox analysis was used to predict the optimal risk model. The protein-protein interaction (PPI) analysis was performed via the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Overall survival (OS) was evaluated in the Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Competing endogenous RNA (ceRNA) network was also visualized using Cytoscape. The expression levels of specific genes were assessed through quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, co-expressed genes and potential biological functions related to specific genes were explored based on the Cancer Cell Line Encyclopedia (CCLE) database. Results: A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones. Using these urinary DEGs and the clinical information of HGBC patients, we developed an optimal risk model consisting of eight genes to predict the patient outcome. By integrating the node degree values in the PPI network with the expression changes in both urine and tissue samples, eighteen hub genes were selected out. Among them, DKC1 and SNRPG had the most prominent comprehensive values, and EFTUD2, LOR and EBNA1BP2 were relevant to a worse OS in bladder cancer patients. The ceRNA network of hub genes indicated that DKC1 may be directly regulated by miR-150 in HGBC. The upregulation of both SNRPG and DKC1 were detected in HGBC cells, which were also observed in various tumor tissues and malignant cell lines, displaying high correlations with other hub genes. Conclusions: Our study may provide theoretical basis for the development of effective non-invasive detection and treatment strategies, and further research is necessary to explore the clinical applications of these findings.

Hsa_circ_0016070/micro-340-5p Axis Accelerates Pulmonary Arterial Hypertension Progression by Upregulating TWIST1 Transcription Via TCF4/ß-Catenin Complex.

Background Hypoxia is considered a major leading cause of pulmonary hypertension (PH). In this study, the roles and molecular mechanism of circ_0016070 in PH were studied. Methods and Results The expression of circ_0016070 in serum samples, human pulmonary artery smooth muscle cells and hypoxia/monocrotaline-treated rats was determined by real-time quantitative polymerase chain reaction. Cell viability, migration, and apoptosis were analyzed by Cell Counting Kit-8, wound healing, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays, respectively. The molecular interactions were validated using RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase reporter assays. The levels of phenotype switch-related proteins were evaluated by Western blot and immunohistochemistry. The pathological characteristics were assessed using hematoxylin and eosin staining. circ_0016070 was highly expressed in the serum samples, hypoxia-induced pulmonary artery smooth muscle cells and pulmonary arterial tissues of PH rats. Downregulation of circ_0016070 ameliorated the excessive proliferation, migration, vascular remodeling, and phenotypic transformation but enhanced cell apoptosis in the PH rat model. In addition, micro (miR)-340-5p was verified as a direct target of circ_0016070 and negatively regulated TCF4 (transcription factor 4) expression. TCF4 formed a transcriptional complex with ß-catenin to activate TWIST1 (Twist family bHLH transcription factor 1) expression. Functional rescue experiments showed that neither miR-340-5p inhibition nor TWIST1 or TCF4 upregulation significantly impeded the biological roles of circ_0010670 silencing in PH. Conclusions These results uncovered a novel mechanism by which circ_0016070 play as a competing endogenouse RNA of miR-340-5p to aggravate PH progression by promoting TCF4/ß-catenin/TWIST1 complex, which may provide potential therapeutic targets for PH.

The MFF-SIRT1/3 axis, regulated by miR-340-5p, restores mitochondrial homeostasis of hypoxia-induced pulmonary artery smooth muscle cells.

Mitochondrial dynamics and quality control play a central role in the maintenance of the proliferation-apoptosis balance, which is closely related to the progression of pulmonary arterial hypertension (PAH). However, the exact mechanism of this balance remains unknown. Pulmonary artery smooth muscle cells (PASMCs) were cultured in hypoxia condition for constructing a PAH model in vitro. The expression of genes and proteins were determined by qRT-PCR and western bolt assays. Cell proliferation-apoptosis balance were tested by MTT, EdU and TUNEL assays. The mitochondrial functions were assessed by flow cytometry, JC-1, Mito tracker red staining, and corresponding kits. Besides, the molecular interaction was validated by dual-luciferase reporter assay. MFF was overexpressed in hypoxia-treated PAMSCs. Knockdown of MFF significantly repressed the excessive proliferation but enhanced cell apoptosis in hypoxia-treated PAMSCs. Moreover, MFF silencing improved mitochondrial function of hypoxia-treated PAMSCs by increasing ATP production and decreasing ROS release and mitochondrial fission. Mechanistically, MFF was a directly target of miR-340-5p, and could negatively regulate SIRT1/3 expression. Subsequently, functional rescue assays showed that the biological effects of MFF in hypoxia-treated PAMSCs were negatively regulated by miR-340-5p and depended on the regulation on SIRT1/3 pathway. These results provided evidences that miR-340-5p regulated MFF-SIRT1/3 axis to improve mitochondrial homeostasis and proliferation-apoptosis imbalance of hypoxia-treated PAMSCs, which provided a theoretical basis for the prevention and treatment of PAH.

Fis1 phosphorylation by Met promotes mitochondrial fission and hepatocellular carcinoma metastasis.

Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.

Epithelioid sarcoma of the parapharyngeal space: A case report.

Epithelioid sarcoma (ES) was first described by Enzinger in 1970. It is a rare variant of soft tissue sarcoma with a 5-year overall survival (OS) rate of 50%. Here, we reported a case of epithelioid sarcoma in the parapharyngeal space of an adult, resulting in a favorable prognosis after chemotherapy and radiation therapy. A 34-year-old female who complained of pharynx pain and discomfort was suspected of having a tumor in the right parapharyngeal space by CT scan. Excision biopsy suggested epithelioid sarcoma. Clinical and radiological studies did not reveal tumor distant metastasis in the patient. After excisional biopsy, the patient underwent chemotherapy and external beam radiation treatment. She has remained alive for 2 years and 7 months without recurrence since her last treatment. In this paper, we also provide a detailed review of the role of radiotherapy in the treatment of epithelioid sarcoma in previously reported cases.

miR-454-3p prevents ox-LDL-induced apoptosis in HAECs by targeting TRPC3.

Endothelial-cell (EC) apoptosis serves a vital role in the pathogenesis of atherosclerosis. Accumulating evidence has implicated microRNA (miRNA/miR) dysregulation in EC apoptosis. Although the role of miR-454-3p in carcinogenesis has been well documented, its role and underlying mechanism in EC apoptosis remain unclear. In the present study, the results revealed that miR-454-3p expression was substantially downregulated in human aortic endothelial cells (HAECs) following oxidized low-density lipoprotein (ox-LDL) treatment. miR-454-3p suppression significantly attenuated the viability of HAECs, while miR-454-3p overexpression repressed ox-LDL-induced HAEC apoptosis. Bioinformatics analysis and luciferase reporter assays revealed that transient receptor potential canonical 3 (TRPC3), a key regulator of atherosclerosis development, was the direct target of miR-454-3p. Furthermore, TRPC3 overexpression abolished the anti-apoptotic effect of miR-454-3p on HAECs. These results revealed a novel role of miR-454-3p in ox-LDL-induced apoptosis in HAECs.

An autophagic gene-based signature to predict the survival of patients with low-grade gliomas.

BACKGROUND: Since autophagy remains an important topic of investigation, the RNA-sequence profiles of autophagy-related genes (ARGs) can provide insights into predicting low-grade gliomas (LGG) prognosis. METHODS: The RNA-seq profiles of autophagic genes and prognosis data of LGG were integrated from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model were carried out to identify the differentially expressed prognostic autophagy-related genes. Then, the autophagic-gene signature was formed and verified in TCGA test set and external CGGA cohorts. Time-dependent receiver operating characteristic (ROC) was examined to test the accuracy of this signature feature. A nomogram was conducted to meet the needs of clinicians. Sankey diagrams were performed to visualize the relationship between the multigene signatures and clinic-pathological features. RESULTS: Twenty-four ARGs were finally identified most relevant to LGG prognosis. According to the specific prediction index formula, the patients were classified into low-risk or high-risk groups. Prognostic accuracy was proved by time-dependent ROC analysis, with AUC 0.9, 0.93, and 0.876 at the survival time of 2-, 3-, and 5-year, respectively, which was superior to the AUC of the isocitrate dehydrogenase (IDH) mutation. The result was confirmed while validated in the TCGA test set and external validation CGGA cohort. A nomogram was constructed to meet individual needs. With a visualization approach, Sankey diagrams show the relationship of the histological type, IDH status, and predict index. In TCGA and CGGA cohorts, both low-risk groups displayed better survival rate in LGG while histological type and IDH status did not show consistency results. CONCLUSIONS: 24-ARGs may play crucial roles in the progression of LGG, and LGG patients were effectively divided into low-risk and high-risk groups according to prognostic prediction. Overall, our study will provide novel strategies for clinical applications.

Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage.

The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.

A Distributed Radio Beacon/IMU/Altimeter Integrated Localization Scheme with Uncertain Initial Beacon Locations for Lunar Pinpoint Landing.

As a growing number of exploration missions have successfully landed on the Moon in recent decades, ground infrastructures, such as radio beacons, have attracted a great deal of attention in the design of navigation systems. None of the available studies regarding integrating beacon measurements for pinpoint landing have considered uncertain initial beacon locations, which are quite common in practice. In this paper, we propose a radio beacon/inertial measurement unit (IMU)/altimeter localization scheme that is sufficiently robust regarding uncertain initial beacon locations. This scheme was designed based on the sparse extended information filter (SEIF) to locate the lander and update the beacon configuration at the same time. Then, an adaptive iterated sparse extended hybrid filter (AISEHF) was devised by modifying the prediction and update stage of SEIF with a hybrid-form propagation and a damping iteration algorithm, respectively. The simulation results indicated that the proposed method effectively reduced the error in the position estimations caused by uncertain beacon locations and made an effective trade-off between the estimation accuracy and the computational efficiency. Thus, this method is a potential candidate for future lunar exploration activities.

INS/CNS Deeply Integrated Navigation Method of Near Space Vehicles.

Celestial navigation is required to improve the long-term accuracy preservation capability of near space vehicles. However, it takes a long time for traditional celestial navigation methods to identify the star map, which limits the improvement of the dynamic response ability. Meanwhile, the aero-optical effects caused by the near space environment can lead to the colorization of measurement noise, which affects the accuracy of the integrated navigation filter. In this paper, an INS/CNS deeply integrated navigation method, which includes a deeply integrated model and a second-order state augmented H-infinity filter, is proposed to solve these problems. The INS/CNS deeply integrated navigation model optimizes the attitude based on the gray image error function, which can estimate the attitude without star identification. The second-order state augmented H-infinity filter uses the state augmentation algorithm to whiten the measurement noise caused by the aero-optical effect, which can effectively improve the estimation accuracy of the H-infinity filter in the near space environment. Simulation results show that the proposed INS/CNS deeply integrated navigation method can reduce the computational cost by 50%, while the attitude accuracy is kept within 10" (3 ). The attitude root mean square of the second-order state augmented H-infinity filter does not exceed 5", even when the parameter error increases to 50%, in the near space environment. Therefore, the INS/CNS deeply integrated navigation method can effectively improve the rapid response ability of the navigation system and the filtering accuracy in the near space environment, providing a reference for the future design of near space vehicle navigation systems.

Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22.

Context: Curcumin has antitumor, antioxidative, anti-inflammatory, and anti-proliferative properties.Objective: To investigate the role of miR-22 during curcumin-induced changes in vascular smooth muscle cells (VSMC) and neointima formation in balloon-injured rat abdominal aorta.Materials and methods: Sprague-Dawley rats were randomised to the sham-operated (n = 10), operated control (injured, n = 10), and curcumin treatment (n = 10) groups. miR-22 expression was determined by real-time PCR. SP1 was assessed by western blot and real-time PCR. Rat aortic smooth muscle A7r5 cells were used to determine VSMC proliferation and migration, which were measured by the MTS, EdU staining, Transwell, and wound healing assays.Results: miR-22 levels declined following arterial balloon injury in vivo (48% at 3d, p < 0.05) and serum stimulation in vitro (45% at 24 h, p < 0.01). Functional studies revealed that miR-22 negatively regulated the proliferation and migration of VSMCs by directly targeting the SP1 transcription factor in VSMCs. Curcumin increased the expression of miR-22 (81%, p < 0.05) and decreased the protein expression of SP1 in VSMCs (25%, p < 0.05). miR-22 inhibition was found to attenuate the effects of curcumin on VSMC functions. Curcumin increased miR-22 (46%, p < 0.01), decreased the SP1 protein (19%, p < 0.05), and inhibited vascular neointimal area (48%, p < 0.01) in vivo.Discussion: The miR-22/SP1 pathway is involved in the protective role of curcumin during arterial balloon injury, but the mechanisms remain unclear.Conclusion: miR-22 is involved in the inhibitory effects of curcumin on VSMCs' proliferation, migration and neointima hyperplasia after arterial balloon injury in rats. Curcumin could be used to prevent neointimal hyperplasia after angioplasty.

[Mobilization of Bone Marrow Mesenchymal Stem Cells Inhibits TGF-ß Non-classical Pathway Against Myocardial Fibrosis in Rats].

OBJECTIVE: To observe the relationship between the mechanism of bone marrow stem cell mobilization mediated the myocardial fibrosis inhibition in rats and the non-classical pathway mediated by transforming growth factor-ß (TGF-ß). METHODS: Twenty two Wistar rats were subcutaneously injected with isoproterenol (Iso) to establish the model of myocardial fibrosis, and then were randomly divided into control group and granulocyte colony-stimulating factor (G-CSF)-treat group (GT group). The rats in GT group were subcutaneously injected with recombinant human granulocyte stimulating factor for 5 days, and the control group was injected with normal saline. After 4 weeks, the myocardial structure was observed by pathological staining, the content of serum B type natriuretic peptide (BNP) was detected by ELISA , the expression of type Ⅲ collagen was detected by immunohistochemistry staining and the protein expression level of typeⅠcollagen, TGF-ß, transforming growth factor kinase 1 (TAK1), mitogen-activated protein kinase kinase (MKK) and p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot. RESULTS: Compared with the control group, the serum BNP level, Masson staining collagen deposition, collagen area ratio and the expression of typeⅠcollagen, TGF- ß, TAK1, MKK3 and p38MAPK in the GT group were lower than those in the control group. CONCLUSION: Bone marrow stem cell mobilization can alleviate the degree of myocardial fibrosis in rats, which is related to the inhibition of TGF- ß/TAK1/MKK/p38MAPK pathway.

The efficacy and safety of PD-1/PD-L1 inhibitors in patients with recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

OBJECTIVES: There is currently no effective salvage therapeutic modality that improves the survival outcomes of patients with recurrent or metastatic nasopharyngeal carcinoma. However, the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors may provide clinical benefit for these advanced patients. MATERIALS AND METHODS: The databases, including PubMed, Web of Science, EMBASE and Cochrane Library, were systematically searched up to Nov 5, 2019. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) rate, overall survival (OS) rate, and drug-related adverse events were extracted and pooled meta-analyzed. RESULTS: From 71 search records, eight studies were included in the systematic review, of which three were eligible for final meta-analysis. In recurrent or metastatic nasopharyngeal carcinoma patients treated with anti-PD-1 therapy, the pooled ORR was 27% (95% confidence interval [CI] 19-36%), DCR was 63% (95% CI 50-75%), 6 months PFS rate was 49% (95% CI 40-58%), 1-year PFS rate was 25% (95% CI 19-32%), 1-year OS rate was 61% (95% CI 49-72%). The pooled incidences of any grade and grade ≥ 3 drug-related adverse events were 94% and 20% respectively. CONCLUSION: We present the aggregate response rates, survival rates and incidences of drug-related adverse events for recurrent or metastatic nasopharyngeal carcinoma patients receiving PD-1/PD-L1 blockage treatment, which could provide useful information for future design of clinical studies. There is a need for more randomized controlled studies with head-to-head comparison of PD-1/PD-L1 inhibitors and traditional chemotherapeutic strategies to enable better recommendations for optimal advanced nasopharyngeal carcinoma treatment.

Id-1 Promotes Reendothelialization In The Early Phase After Vascular Injury Through Activation Of NFkB/survivin Signaling Pathway.

BACKGROUND: Percutaneous coronary intervention (PCI) treatment can benefit patients, but also cause irreversible mechanical damage to the vascular endothelium, ultimately leading to restenosis of the target vessel. Thus, achieving rapid re-endothelialization and restoring the integrity of the vascular endothelium and function plays an important role in inhibiting neointimal hyperplasia and preventing restenosis. Id1 (inhibitor of DNA binding/differentiation factor 1) plays an important role in promoting cell proliferation and angiogenesis. STUDY OBJECTIVE: This study aims to investigate the relationship between Id1 and NFκB/survivin signaling pathways and their role in injured vascular repair by establishing a rat carotid balloon injury model. METHODS: The carotid artery model of rat balloon injury was established. The injured common carotid artery was obtained at different time points after vascular injury. RNA and protein were extracted and the mRNA and protein expression levels of Id1, NFκB and survivin were detected in vascular injury. The NFκB blocker BAY 11-7082 and survivin blocker YM155 were used and the effects of Id1, NFκB, survivin mRNA and protein expression, revascularization of blood vessels and neointimal responsiveness after vascular injury were observed in the vascular tissues of Ad-Id1 transfected balloon injury. RESULTS: Id1, NFκB and survivin were expressed in injured rat carotid arteries. Overexpression of Id1 promoted re-endothelialization of injured vessels through NFκB/survivin signaling pathway, inhibited early vascular endometrial reactive hyperplasia; blocked NFκB the/survivin signaling pathway attenuates the re-endothelialization of Ad-Id1 and the early endothelium of Ad-Id1. Blocking the NFκB/survivin signaling pathway attenuates the re-endothelialization and early reactive hyperplasia of vascular intima of Ad-Id1. CONCLUSION: NF-kappa B/survivin signaling pathway may play an important role in Id1 promoting vascular re-endothelialization, inhibiting neointimal hyperplasia and preventing vascular restenosis.

Enhancing superconductivity in SrTiO3 films with strain.

The nature of superconductivity in SrTiO3, the first oxide superconductor to be discovered, remains a subject of intense debate several decades after its discovery. SrTiO3 is also an incipient ferroelectric, and several recent theoretical studies have suggested that the two properties may be linked. To investigate whether such a connection exists, we grew strained, epitaxial SrTiO3 films, which are known to undergo a ferroelectric transition. We show that, for a range of carrier densities, the superconducting transition temperature is enhanced by up to a factor of two compared to unstrained films grown under the same conditions. Moreover, for these films, superconductivity emerges from a resistive state. We discuss the localization behavior in the context of proximity to ferroelectricity. The results point to new opportunities to enhance superconducting transition temperatures in oxide materials.

Antiplatelet Effect of Different Loading Doses of Ticagrelor in Patients With Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The APELOT Trial.

BACKGROUND: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events. RESULTS: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization. CONCLUSIONS: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI.

Long-term nicotine exposure induces dysfunction of mouse endothelial progenitor cells.

Endothelial progenitor cells (EPCs) have an important role in maintaining endothelial homeostasis. Previous studies reported that smoking has detrimental effects on EPCs; however, recent studies revealed that short-term nicotine exposure may benefit EPCs. As most smokers are exposed to nicotine over an extended time period, the present study aimed to investigate the long-term effects of nicotine on EPCs. Mice were administered nicotine orally for 1, 3 or 6 months. The mice exposed to nicotine for 1 month demonstrated increased EPC counts and telomerase activity and reduced cell senescence compared with control mice, consistent with previous reports. However, long-term nicotine exposure resulted in opposing effects on EPCs, causing decreased counts, functional impairment and reduced telomerase activity. Furthermore, the effects of nicotine exposure were correlated with changes in sirtuins type 1 (SIRT1) protein expression. The current study indicated that long-term nicotine exposure induces dysfunction and senescence of EPCs, which may be associated with impairment of telomerase activity through SIRT1 downregulation. The present results emphasize the necessity of smoking cessation to prevent dysfunction of EPCs.

Recent advances of adapter proteins in the regulation of heart diseases.

Heart diseases are major causes of mortality. Cardiac hypertrophy, myocardial infarction (MI), viral cardiomyopathy, ischemic and reperfusion (I/R) heart injury finally lead to heart failure and death. Insulin and IGF1 signal pathways play key roles in normal cardiomyocyte growth and physiological cardiac hypertrophy while inflammatory signal pathway is associated with pathological cardiac hypertrophy, MI, viral cardiomyopathy, I/R heart injury, and heart failure. Adapter proteins are the major family proteins, which transduce signals from insulin, IGF1, or cytokine receptors to the downstream pathways and have been shown to regulate variety of heart diseases. Here, we summarized the recent advances in understanding the physiological and pathological roles of adapter proteins in heart failure.