Orietation-controlled synthesis and Raman study of 2D SnTe.

Tin telluride (SnTe), as a narrow bandgap semiconductor material, has great potential for developing photodetectors with wide spectra and ultra-fast response. At the same time, it is also an important topological crystal insulator material, with different topological surface states on several common surfaces. Here, we introduce different Sn sources and control the growth of regular SnTe nanosheets along the (100) and (111) planes through the atmospheric pressure chemical vapor deposition method. It has been proven through various characterizations that the synthesized SnTe is a high-quality single crystal. In addition, the angular resolved Raman spectra of SnTe nanosheets grown on different crystal planes are first demonstrated. The experimental results showed that square SnTe nanosheets grown along the (100) plane exhibit in-plane anisotropy. At the same time, we use micro-nanofabrication technology to manufacture SnTe-based field effect transistors and photodetectors to explore their electrical and optoelectronic properties. It has been confirmed that transistors based on grown SnTe nanosheets exhibit p-type semiconductor characteristics and have a high response to infrared light. This work provides a new approach for the controllable synthesis of SnTe and adds new content to the research of SnTe-based infrared detectors.

Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury.

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.

Growth, Raman Scattering Investigation and Photodetector Properties of 2D SnP.

As an important metal phosphides material, 2D tin phosphides (SnPx 0 <  x ≤ 3) have been theoretically predicted to have intriguing physicochemical properties and potential applications in electronics, optoelectronics, and energy fields. However, the synthesis of high-quality 2D SnP single crystal has not been reported due to the lack of efficiency and reliable growth method. Here, a facile atmospheric pressure chemical vapor deposition (APCVD) method is developed to realize the growth of high-quality 2D SnP nanosheets, by employing tin (Sn) foil as both liquid metal substrates and reaction precursor. Temperature-dependent and angle-resolved polarization Raman spectra observed Raman peaks located at 142.6, 303.3, and 444.2 cm-1 are concluded to belong to A1g mode, which are consistent with the theoretical calculation results. Moreover, the field-effect transistor (FET) devices based on SnP nanosheets show a typical n-type characteristic with an on/off ratio of 103 at 200 K. SnP nanosheets also demonstrate excellent photoresponse performance under the illumination of 473, 532, and 639 nm lasers, which can be tuned by Vgs , Vds , and light power density. It is believed that these findings can provide the first-hand experimental information for the future study of 2D SnP nanosheets.

Dapagliflozin Attenuates Contrast-induced Acute Kidney Injury by Regulating the HIF-1α/HE4/NF-κB Pathway.

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies have shown that hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits hypoxia-inducible factor (HIF)-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia + pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis, and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry, respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, human epididymis protein 4 (HE4), NF-κB expression, and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media, and diabetes + contrast media + dapagliflozin groups. Rats in the latter 2 groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-l-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in diabetes + contrast media rats compared with C, D, and diabetes + dapagliflozin + contrast media rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.

METTL3 mediates Ang-II-induced cardiac hypertrophy through accelerating pri-miR-221/222 maturation in an m6A-dependent manner.

BACKGROUND: METTL3 is the core catalytic enzyme in m6A and is involved in a variety of cardiovascular diseases. However, whether and how METTL3 plays a role during angiotensin II (Ang-II)-induced myocardial hypertrophy is still unknown. METHODS: Neonatal rat cardiomyocytes (NRCMs) and C57BL/6J mice were treated with Ang-II to induce myocardial hypertrophy. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. Gene function was verified by knockdown and/or overexpression, respectively. Luciferase and RNA immunoprecipitation (RIP) assays were used to verify interactions among multiple genes. Wheat germ agglutinin (WGA), hematoxylin and eosin (H&E), and immunofluorescence were used to examine myocardial size. m6A methylation was detected by a colorimetric kit. RESULTS: METTL3 and miR-221/222 expression and m6A levels were significantly increased in response to Ang-II stimulation. Knockdown of METTL3 or miR-221/222 could completely abolish the ability of NRCMs to undergo hypertrophy. The expression of miR-221/222 was positively regulated by METTL3, and the levels of pri-miR-221/222 that bind to DGCR8 or form m6A methylation were promoted by METTL3 in NRCMs. The effect of METTL3 knockdown on hypertrophy was antagonized by miR-221/222 overexpression. Mechanically, Wnt/ß-catenin signaling was activated during hypertrophy and restrained by METTL3 or miR-221/222 inhibition. The Wnt/ß-catenin antagonist DKK2 was directly targeted by miR-221/222, and the effect of miR-221/222 inhibitor on Wnt/ß-catenin was abolished after inhibition of DKK2. Finally, AAV9-mediated cardiac METTL3 knockdown was able to attenuate Ang-II-induced cardiac hypertrophy in mouse model. CONCLUSIONS: Our findings suggest that METTL3 positively modulates the pri-miR221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/ß-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy. AAV9-mediated cardiac METTL3 knockdown could be a therapeutic for pathological myocardial hypertrophy.

High serum fibroblast growth factor 21 levels were related to the prognosis and ventricular remodeling of heart failure patients with mildly reduced and reduced ejection fraction.

INTRODUCTION: Previous studies have shown that fibroblast growth factor 21 (FGF21) is involved in the ventricular remodeling process in heart failure with preserved ejection fraction (HFpEF). We hypothesized that high levels of FGF21 correlated with the ventricular remodeling of heart failure patients with mildly reduced (HFmrEF) and reduced ejection fraction (HFrEF). METHODS: A total of 203 participants with HFmrEF or HFrEF were enrolled and followed up from June 2018 to June 2021. 68 subjects without heart failure (HF) underwent physical examinations during the same time were selected as the control group. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), which were defined as all-cause or cardiac mortality and rehospitalization for decompensation. Serum FGF21 levels were measured early the next morning after admission using enzyme-linked immunosorbent assay (ELISA). RESULTS: The FGF21 levels were significantly higher in patients with HFmrEF or HFrEF than that in the control group (213.57 ± 42.65 pg/mL, 222.93 ± 34.36 pg/mL vs 171.00 ± 12.86 pg/mL, p < .001). The serum levels of FGF21 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were both higher in the endpoint event group than those of non-endpoint event group regardless of the HFmrEF or HFrEF group (p < .001). Spearman's correlation revealed that FGF21 was positively correlated with left ventricular end-systolic diameter left ventricular end-diastolic diameter left ventricular mass index (p < .01). Moreover, there was a negative correlation between FGF21 and left ventricular ejection fraction in addition to relative wall thickness (p < .001). The area under the receiver operating characteristic (ROC) curve (AUC) of FGF21 was 0.874. The optimal cut-off value of FGF21 determined by ROC curve was 210.11 pg/mL. The Kaplan-Meier analysis demonstrated that the low FGF21 levels group had an increased MACE-free survival rate compared with the high FGF21 levels group. On univariate and multivariate Cox analysis, it was seen that both serum FGF21 and NT-proBNP were independent predictors of a poor prognosis in HF patients. CONCLUSION: Baseline levels of FGF21 and NT-proBNP were related to the ventricular remodeling of patients with a mildly reduced or reduced ejection fraction. FGF21 and NT-proBNP both had good prognostic value for MACEs in heart failure patients with a mildly reduced and reduced ejection fraction.

Protective role of serpina3c as a novel thrombin inhibitor against atherosclerosis in mice.

Abnormal vascular smooth muscle cell (VSMC) proliferation is a critical step in the development of atherosclerosis. Serpina3c is a serine protease inhibitor (serpin) that plays a key role in metabolic diseases. The present study aimed to investigate the role of serpina3c in atherosclerosis and regulation of VSMC proliferation and possible mechanisms. Serpina3c is down-regulated during high-fat diet (HFD)-induced atherosclerosis. An Apoe-/-/serpina3c-/--double-knockout mouse model was used to determine the role of serpina3c in atherosclerosis after HFD for 12 weeks. Compared with Apoe-/- mice, the Apoe-/-/serpina3c-/- mice developed more severe atherosclerosis, and the number of VSMCs and macrophages in aortic plaques was significantly increased. The present study revealed serpina3c as a novel thrombin inhibitor that suppressed thrombin activity. In circulating plasma, thrombin activity was high in the Apoe-/-/serpina3c-/- mice, compared with Apoe-/- mice. Immunofluorescence staining showed thrombin and serpina3c colocalization in the liver and aortic cusp. In addition, inhibition of thrombin by dabigatran in serpina3c-/- mice reduced neointima lesion formation due to partial carotid artery ligation. Moreover, an in vitro study confirmed that thrombin activity was also decreased by serpina3c protein, supernatant and cell lysate that overexpressed serpina3c. The results of experiments showed that serpina3c negatively regulated VSMC proliferation in culture. The possible mechanism may involve serpina3c inhibition of ERK1/2 and JNK signaling in thrombin/PAR-1 system-mediated VSMC proliferation. Our results highlight a protective role for serpina3c as a novel thrombin inhibitor in the development of atherosclerosis, with serpina3c conferring protection through the thrombin/PAR-1 system to negatively regulate VSMC proliferation through ERK1/2 and JNK signaling.

Recent progress on emergent two-dimensional magnets and heterostructures.

Intrinsic two-dimensional (2D) magnetic materials own strong long-range magnetism while their characteristics of the ultrathin thickness and smooth surface provide an ideal platform for manipulating the magnetic properties at 2D limit. This makes them to be potential candidates in various spintronic applications compared to their corresponding bulk counterparts. The discovery of magnetic ordering in 2D CrI3and Gr2Ge2Te6nanostructures stimulated tremendous research interest in both experimental and theoretical studies on various intrinsic magnets at 2D limit. This review gives a comprehensive overview of the recent progress on the emergent 2D magnets and heterostructures. Firstly, several kinds of typical 2D magnetic materials discovered in the last few years and their fabrication methods are summarized in detail. Secondly, the current strategies for manipulating magnetic properties in 2D materials are further discussed. Then, the recent advances on the construction of representative van der Waals magnetic heterostructures and their respective performance are provided. With the hope of motivating the researchers in this area, we finally offered the challenges and outlook on 2D magnetism.

Fibroblast Growth Factor 21 Correlates with the Prognosis of Dilated Cardiomyopathy.

OBJECTIVES: The goal of this study was to evaluate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the prognosis of dilated cardiomyopathy (DCM). METHODS: 241 patients with DCM and 80 control subjects were recruited and followed up for an average of 16.12 months. A 2-dimensional (2-D) echocardiography technique was performed to calculate the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) percentages. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatinine were measured in routine clinical laboratory tests. Serum FGF21 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of serum FGF21 were significantly higher in the DCM groups than in the control groups (225.85 ± 32.57 vs. 145.36 ± 30.57, p < 0.001). Serum FGF21 levels were positively correlated with the NYHA functional classification of heart failure (HF) (r = 0.610, p < 0.001) and NT-proBNP levels (r = 0.741, p < 0.001). Moreover, a negative correlation was observed between the serum FGF21 levels and the LVEF (r = -0.402, p < 0.001). FGF21, NT-proBNP, the LVEF and a history of atrial fibrillation (AF) correlated significantly with NYHA class IV (p < 0.05). The AUC of NT-proBNP for predicting NYHA class IV in DCM patients was greater than that of FGF21 (0.830 vs. 0.772, p < 0.001). Overall, 133 patients with DCM were recorded at the end point. Kaplan-Meier analysis results showed that the survival probability of those individuals with high levels of FGF21 and NT-proBNP was significantly lower than of those with low levels of these factors (p < 0.001). In the multivariate Cox analysis, FGF21 (HR 2.561; 95% CI 1.705-3.849) and NT-proBNP (HR 4.458; 95% CI 2.645-7.513) were independent predictors of a poor prognosis in DCM patients. CONCLUSIONS: Serum FGF21 levels were associated with the risk factors, severity, and prognosis of DCM. Therefore, FGF21 may serve as a novel biomarker for the prognosis of DCM.

Tunable Room-Temperature Ferromagnetism in Two-Dimensional Cr2Te3.

The manipulation of magnetism provides a unique opportunity for the development of data storage and spintronic applications. Until now, electrical control, pressure tuning, stacking structure dependence, and nanoscale engineering have been realized. However, as the dimensions are decreased, the decrease of the ferromagnetism phase transition temperature (Tc) is a universal trend in ferromagnets. Here, we make a breakthrough to realize the synthesis of 1 and 2 unit cell (UC) Cr2Te3 and discover a room-temperature ferromagnetism in two-dimensional Cr2Te3. The newly observed Tc increases strongly from 160 K in the thick flake (40.3 nm) to 280 K in 6 UC Cr2Te3 (7.1 nm). The magnetization and anomalous Hall effect measurements provided unambiguous evidence for the existence of spontaneous magnetization at room temperature. The theoretical model revealed that the reconstruction of Cr2Te3 could result in anomalous thickness-dependent Tc. This dimension tuning method opens up a new avenue for manipulation of ferromagnetism.

Insulin secretion impairment induced by rosuvastatin partly though autophagy in INS-1E cells.

Statins are used extensively for the clinical treatment of cardiovascular diseases. Recent studies suggest that statins increase the risk of new-onset diabetes mellitus (NODM). However, the mechanisms of statin-induced NODM remain unclear. The present study investigated the effects of autophagy on insulin secretion impairment induced by rosuvastatin (RS) in rat insulinoma cells (INS-1E) cells. INS-1E cells were cultured and treated with RS at different concentrations (0.2-20 µM) for 24 h. Insulin secretion in INS-1E cells was detected by enzyme-linked immunosorbent assay, and the co-localization of microtubule-associated protein light chain 3 (LC3) and lysosome-associated membrane protein 2 (LAMP-2) was observed by immunofluorescence staining. Western blotting was used to assess the conversion of LC3 and p62. The results showed that the insulin secretion and cell viability decrease induced by RS treatment for 24 h occurred in a dose-dependent manner in INS-1E cells. RS significantly inhibited the expression of LC3-II but increased the protein expression of p62. Simultaneously, RS diminished the co-localization of LC3-II and LAMP-2 fluorescence signals. These results suggested that RS-inhibited autophagy in INS-1E cells. Rapamycin, an autophagy agonist, reversed the insulin secretion and cell viability suppression induced by RS in INS-1E cells. RS also decreased the phosphorylation of the mammalian target of rapamycin (mTOR). The results indicated that RS impairs insulin secretion in INS-1E cells, which may be partly due to the inhibition of autophagy via an mTOR-dependent pathway.

Evaluation of a smart activatable MRI nanoprobe to target matrix metalloproteinases in the early-stages of abdominal aortic aneurysms.

Matrix metalloproteinases (MMPs) activation contributes to abdominal aortic aneurysm (AAA) growth and rupture. The study was to evaluate the ability of a novel activatable magnetic resonance imaging (MRI) nanoprobe, to target MMPs in an Angiotensin II (ANG II)-induced AAA model. The activatable nanoprobe is composed of a hydrophilic polyethylene glycol coating layer immobilized on the external surface of core/shell Fe/iron oxide nanoparticles; between them, there was grafted the MMP peptide substrate. In the ANG II infusion mice model of AAAs, MRI was performed to characterize the progression of model. The contrast-to-noise ratio was lower in the aneurysm of the mice injected with activatable nanoprobe. Histological studies revealed the presence of MMPs and iron-oxide in regions of MR signal decrease. MRI combined with nanoprobe allows the detection of MMP activity within the wall of AAA, thus representing a potential noninvasive method to predict the rupture risk of AAA.

Bradykinin protects cardiac c-kit positive cells from high-glucose-induced senescence through B2 receptor signaling pathway.

Cardiac c-kit positive cells are cardiac-derived cells that exist within the heart and have a great many protective effects. The senescence of cardiac c-kit positive cells probably leads to cell dysfunction. Bradykinin plays a key role in cell protection. However, whether bradykinin prevents cardiac c-kit positive cells from high-glucose-induced senescence is unknown. Here, we found that glucose treatment causes the premature senescence of cardiac c-kit positive cells. Bradykinin B2 receptor (B2R) expression was declined by glucose-induced senescence. Bradykinin treatment inhibited senescence and reduced intracellular oxygen radicals according to senescence-associated ß-galactosidase staining and 2',7'-dichlorodihydrofluorescein diacetate staining. Moreover, the mitochondrial membrane potential was damaged, as measured by JC-1 staining. The mitochondrial membrane potential was preserved under bradykinin treatment. The concentration of superoxide was decreased, and the concentration of intracellular adenosine triphosphate was increased after bradykinin treatment. Western blot showed that bradykinin leads to AKT and mammalian target of rapamycin (mTOR) phosphorylation and decreased levels of P53 and P16 when compared with glucose treatment alone. Antagonists of B2R, phosphoinositide 3-kinase (PI3K), mTOR, and B2R small interfering RNA prevented the protective effect of bradykinin. P53 antagonist also inhibited the glucose-induced senescence of cardiac c-kit positive cells. In conclusion, bradykinin prevents the glucose-induced premature senescence of cardiac c-kit positive cells through the B2R/PI3K/AKT/mTOR/P53 signal pathways.

MicroRNA-7b attenuates ischemia/reperfusion-induced H9C2 cardiomyocyte apoptosis via the hypoxia inducible factor-1/p-p38 pathway.

OBJECTIVE: MicroRNAs (miRNAs) have been shown to play crucial roles in the occurrence, development, and treatment of many cardiovascular diseases. Coronary heart disease (CAD)-related miRNAs are still a growing research area. miR-7b was reported to be downregulated in acute myocardial infarction (AMI) myocardium tissues. However, it remains largely unknown whether miR-7b is involved in the pathogenesis and progression of the AMI ischemia/reperfusion (I/R) injury. METHODS: Male C57BL/6 J mice and H9C2 cells were used as models in this study. Masson staining, real-time polymerase chain reaction, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling immunofluorescence staining assays were performed to detect the related indicators in the study. SPSS 17.0 software was used to calculate the experimental data. RESULTS: The results showed that miR-7b expression is downregulated after I/R in mice, and miR-7b could inhibit apoptosis in I/R-induced H9C2 cells via upregulating hypoxia-inducible factor 1a (HIF1a). The inhibitory effect of miR-7b on I/R-induced apoptosis in H9C2 cells was blocked by HIF1a silencing. In addition, our data suggested that the p-P38 pathway may be involved in the role of miR-7 in I/R-induced H9C2 cell apoptosis. CONCLUSION: We confirmed that the overexpression of miR-7b inhibits I/R-induced apoptosis in H9C2 cells by targeting the HIF1a/p-P38 pathway. Our findings not only demonstrate the potential role of miR-7b in attenuating I/R-induced apoptosis but also provide a new insight into the better prevention of the I/R injury by mediating HIF-1 and p-P38.

Photoacoustic Imaging: A Novel Tool for Detecting Carotid Artery Thrombosis in Mice.

Thrombosis is a main cause of acute cardiovascular events, and detecting thrombi in small arteries via noninvasive imaging remains challenging. In this study, we employed a novel imaging method, photoacoustic imaging (PAI), to study thrombosis in a mouse model of ferric chloride (FeCl3)-induced arterial thrombosis and compared the ability of this method to detect thrombosis with that of a conventional imaging method, namely, ultrasound. The mice (n = 20) were divided equally into the following 4 groups: (1) a normal group, and (2) 3 experimental groups, in which the left common carotid artery was treated with 20% FeCl3 for 1, 3, or 5 min, respectively. After 24 h, PAI detected thrombi of different sizes and generated images, enabling us to assess the changes in structure. The results of this study suggest that PAI is a useful, noninvasive visualization tool for investigating the mechanism underlying thrombosis development and is suitable for imaging arterial thrombosis in mouse carotid arteries.

Erythropoietin Attenuates Cardiac Dysfunction in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Diabetic Cardiomyopathy.

PURPOSE: Enhanced endoplasmic reticulum (ER) stress and down-regulated SERCA2a expression play crucial roles in diabetes. We aimed to verify whether erythropoietin (EPO) attenuates cardiac dysfunction by suppressing ER stress in diabetic rats. METHODS: Forty male SD rats were randomly divided into four groups: control, EPO-treated control, vehicle-treated diabetic, and EPO-treated diabetic groups. The animals in the EPO-treated control and diabetic groups were administered recombinant human EPO (1000 U/kg body weight) once per week for 12 weeks. RT-PCR and Western blotting assays were performed to detect the expression of 78-kDa glucose-regulated protein precursor (GRP78) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a). We cultured neonatal rat cardiomyocytes and investigated the protective effects of EPO against high glucose (HG)-induced apoptosis. Intracellular calcium levels were measured through confocal microscopy. RESULTS: We observed increased myocardial GRP78 expression and decreased myocardial SERCA2a expression in diabetic rats. EPO prevented the changes in GRP78, SERCA2a expression and cardiac dysfunction in diabetic rats. The levels of GRP78 protein were significantly reduced in EPO-treated diabetic rats compared with vehicle-treated diabetic rats (GRP78 protein 0.09 ± 0.03 vs. 0.54 ± 0.04, P < 0.01). The levels of the SERCA2a proteins were significantly increased in EPO-treated diabetic rats compared with vehicle-treated diabetic rats (SERCA2a protein 0.60 ± 0.05 vs. 0.13 ± 0.04, P < 0.01). A reduction in apoptosis was observed in the cardiomyocytes treated with 20 U/mL EPO compared with the cardiomyocytes cultured under HG conditions (apoptosis rate 18.9 ± 1.94 vs. 37.9 ± 1.59%, P < 0.01). CONCLUSIONS: This study demonstrates that EPO treatment improved the parameters of cardiac function following HG-induced injury by suppressing ER stress and inducing SERCA2a expression.

Anti-connective tissue growth factor detects and reduces plaque inflammation in early-stage carotid atherosclerotic lesions.

This study explored connective tissue growth factor (CTGF)-targeted ultrasmall superparamagnetic iron oxides (USPIOs) for noninvasive MRI of CTGF within carotid atherosclerotic lesions in apoE-deficient (apoE-/-) mice. Anti-CTGF polyclonal and nonspecific IgG antibodies were conjugated to polyethylene glycol-coated USPIOs, and apoE-/- carotid partial ligation-model mice were imaged via MRI before and after contrast administration. ApoE-/- mice were treated with CTGF-neutralizing antibodies for 3 weeks. Carotid artery diameter and plaque volume were measured via MRI in IgG and CTGF antibody-treated groups. Anti-CTGF-USPIO-treated macrophages showed the greatest iron uptake. MRI signal loss was observed in carotid atherosclerotic lesions 24 h after anti-CTGF-USPIO administration, consistent with the presence of nanoparticles, as indicated by pathological examinations. Atheromata in anti-CTGF-treated mice showed reduced macrophage deposition, CTGF expression, and plaque volume. Anti-CTGF-USPIOs can be used for the direct detection of CTGF and imaging of atherosclerotic lesions in vivo. CTGF is a potential therapeutic target for treating atherosclerosis.

Contralateral artery enlargement predicts carotid plaque progression based on machine learning algorithm models in apoE-/- mice.

BACKGROUND: This study specifically focused on anatomical MRI characterization of the low shear stress-induced atherosclerotic plaque in mice. We used machine learning algorithms to analyze multiple correlation factors of plaque to generate predictive models and to find the predictive factor for vulnerable plaque. METHODS: Branches of the left carotid artery in apoE-/- and C57BL/6J mice were ligated to produce the partial left carotid artery model. Before surgery, and 7, 14, and 28 days after surgery, in vivo serial MRI measurements of carotid artery diameter were obtained. Meanwhile, proximal blood flow was evaluated. After image acquisition and animal sacrifice, carotid arteries were harvested for histological analysis. Support vector machine (SVM) and decision tree (DT) were used to select features and generate predictive models of vulnerable plaque progression. RESULT: Seven days after surgery, neointima formation was visualized on micro-MRI in both apoE-/- and C57BL/6J mice. Ultrasonography showed that blood flow had significantly decreased compared to that in the contralateral artery. Partial ligation of the carotid artery for 4 weeks in apoE-/- mice induced vulnerable plaque; however, in C57BL/6J mice this same technique performed for 4 weeks induced arterial stenosis. Contralateral carotid artery diameter at 7 days after surgery was the most reliable predictive factor in plaque progression. We achieved over 87.5% accuracy, 80% sensitivity, and 95% specificity with SVM. The accuracy, sensitivity, and specificity for the DT classifier were 90, 90, and 90%, respectively. CONCLUSIONS: This study is the first to demonstrate that SVM and DT methods could be suitable models for identifying vulnerable plaque progression in mice. And contralateral artery enlargement can predict the vulnerable plaque in carotid artery at the very early stage. It may be a valuable tool which helps to optimize the clinical work flow process by providing more decision in selecting patients for treatment.

Magnetic field assisted programming of particle shapes and patterns.

Anisotropic particles have generated an enormous amount of research interest due to their applications for drug delivery, electronic displays and as micromotors. However, up till now, there is no single protocol capable of generating particles of "patchy" composition with a variety of well-defined and predictable shapes. To address this, in this submission we dispersed magnetic nanoparticles (MNPs) in a non-magnetic fluid containing monomer and crosslinker. This solution was added to the surface of Teflon, which was submerged in the solvent 2,2,4-trimethylpentane. Under these conditions a round, stable droplet was formed on the Teflon. Upon exposure to a permanent magnet, the MNPs self-assembled into clusters with a variety shapes and sizes. The shape and size of the clusters depended on the magnetic field strength, which we controlled by systematically varying the distance between the magnet and the droplet. Interestingly, the shape of the liquid droplet was also influenced by the magnetic field. Upon polymerization, the MNP patterns and the droplet shape was preserved. We also show that very complex MNP patterns and particle shapes could be generated by controlling the distance between the drop and both a magnet above and below the droplet. In this case, the resulting patterns depended on whether the magnets were attracting or repelling each other, which was capable of changing the field lines that the MNPs align with. Overall, this approach is capable of generating particles with predictable MNP patterns and particle shapes without the use of any templates or complex synthetic steps. Furthermore, by using a sprayer (or similar approaches, e.g., ink jet printing) this technique can be easily scaled up to produce many complex anisotropic particles in a short amount of time.

Regulation of c-kit+ progenitor cells by stromal cell derived factor-1α in adult murine heart.

BACKGROUND: c-kit-positive cardiac progenitor cells (CPCs) have been proven suitable for stem cell therapy. CPCs marker c-kit and its ligand, the stem cell factor (SCF), are associated with the functions of proliferation and differentiation. In our previous study, we found that stromal cell-derived factor-1α (SDF-1α) could enhance the expression of c-kit. However, the mechanism is unknown. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts, and c-kit-positive CPCs were purified by magnetic-activated c-kit cell sorting magnetic beads. The cells were cultured with SDF-1α, c-kit expression was measured by western blotting and qPCR, the proliferation and migration of cells were measured by CCK-8 and transwell assay, DNA methyltransferase (DNMT) mRNA were measured by qPCR, global DNMT activity was measured by DNMT activity assay kit, and DNA methylation was analysed using Sequenom's MassARRAY platform. Results showed that SDF-1α could enhance the expression of c-kit, which results in the promoting of c-kit-positive CPCs proliferation and migration. SDF-1α stimulation inhibited the expression of DNMT1, DNMT3ß, and global DNMT activity, which led to significant demethylation in c-kit-positive CPCs. CONCLUSIONS: SDF-1α signalling, via CXCR4 activation, up-regulated c-kit expression by inhibiting DNMT1 and DNMT3ß expression and global DNMT activity, and by subsequent demethylation of the c-kit gene.