BRD4770 inhibits vascular smooth muscle cell proliferation via SUV39H2, but not EHMT2 to protect against neointima formation.

The behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers. However, whether and how BRD4770 regulates the behavior of VSMCs remain unknown. In this study, we evaluate the cellular effect of BRD4770 on VSMCs by series of experiments in vivo and ex vivo. We demonstrated that BRD4770 inhibited VSMCs' growth by blockage in G2/M phase in VSMCs. Moreover, our results demonstrated that the inhibition of proliferation was independent on autophagy or EHMT2 suppression which we previous reported. Mechanistically, BRD4770 exhibited an off-target effect from EHMT2 and our further study reveal that the proliferation inhibitory effect by BRD4770 was associated with suppressing on SUV39H2/KTM1B. In vivo, BRD4770 was also verified to rescue VIH. Thus, BRD4770 function as a crucial negative regulator of VSMC proliferation via SUV39H2 and G2/M cell cycle arrest and BRD4770 could be a molecule for the therapy of vascular restenosis.

In Situ Trapping Strategy Enables a High-Loading Ni Single-Atom Catalyst as a Separator Modifier for a High-Performance Li-S Battery.

The poor electrochemical reaction kinetics of Li polysulfides is a key barrier that prevents the Li-S batteries from widespread applications. Ni single atoms dispersed on carbon matrixes derived from ZIF-8 are a promising type of catalyst for accelerating the conversion of active sulfur species. However, Ni favors a square-planar coordination that can only be doped on the external surface of ZIF-8, leading to a low loading amount of Ni single atoms after pyrolysis. Herein, we demonstrate an in situ trapping strategy to synthesize Ni and melamine-codoped ZIF-8 precursor (Ni-ZIF-8-MA) by simultaneously introducing melamine and Ni during the synthesis of ZIF-8, which can remarkably decrease the particle size of ZIF-8 and further anchor Ni via Ni-N6 coordination. Consequently, a novel high-loading Ni single-atom (3.3 wt %) catalyst implanted in an N-doped nanocarbon matrix (Ni@NNC) is obtained after high-temperature pyrolysis. This catalyst as a separator modifier shows a superior catalytic effect on the electrochemical transitions of Li polysulfides, which endows the corresponding Li-S batteries with a high specific capacity of 1232.4 mA h g-1 at 0.3 C and an excellent rate capability of 814.9 mA h g-1 at 3 C. Furthermore, a superior areal capacity of 4.6 mA h cm-2 with stable cycling over 160 cycles can be achieved under a critical condition with a low electrolyte/sulfur ratio (8.4 µL mg-1) and high sulfur loading (4.85 mg cm-2). The outstanding electrochemical performances can be attributed to the strong adsorption and fast conversion of Li polysulfides on the highly dense active sites of Ni@NNC. This intriguing work provides new inspirations for designing high-loading single-atom catalysts applied in Li-S batteries.

Scalable production of high-performing woven lithium-ion fibre batteries.

Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.

EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation.

Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition of EHMT2 by BIX01294 or knockdown of EHMT2 resulted in reduced VSMC numbers which were independent of proliferation and apoptosis. Interestingly, EHMT2 protein levels were significantly decreased in VSMCs treated with autophagic inducers. Moreover, more autophagic vacuoles and accumulated LC3II were detected in VSMCs treated with BIX01294 or lenti-shEHMT2 than their counterparts. Furthermore, we found that EHMT2 inhibited the ACD of VSMCs by suppressing autophagosome formation. Mechanistically, the pro-autophagic effect elicited by EHMT2 inhibition was associated with SQSTM1 and BECN1 overexpression. Moreover, these detrimental effects were largely nullified by SQSTM1 or BECN1 knockdown. More importantly, similar results were observed in primary human aortic VSMCs. Overall, these findings suggest that EHMT2 functions as a crucial negative regulator of ACD via decreasing SQSTM1 or BECN1 expression and that EHMT2 could be a potent therapeutic target for cardiovascular diseases (e.g., aortic dissection).

Application Challenges in Fiber and Textile Electronics.

Modern electronic devices are moving toward miniaturization and integration with an emerging focus on wearable electronics. Due to their close contact with the human body, wearable electronics have new requirements including low weight, small size, and flexibility. Conventional 3D and 2D electronic devices fail to efficiently meet these requirements due to their rigidity and bulkiness. Hence, a new family of 1D fiber-shaped electronic devices including energy-harvesting devices, energy-storage devices, light-emitting devices, and sensing devices has risen to the challenge due to their small diameter, lightweight, flexibility, and weavability into soft textile electronics. The application challenges faced by fiber and textile electronics from single fiber-shaped devices to continuously scalable fabrication, to encapsulation and testing, and to application mode exploration, are discussed. The evolutionary trends of fiber and textile electronics are then summarized. Finally, future directions required to boost their commercialization are highlighted.

Fluoroquinolone Use and the Risk of Collagen-Associated Adverse Events: A Systematic Review and Meta-Analysis.

INTRODUCTION: It has been suggested that fluoroquinolone antibiotics increase the risk of developing collagen-associated adverse events such as aortic dissection and aortic aneurysm. These are life-threatening emergencies that need to be prevented. OBJECTIVES: We performed this systematic review to clarify the association between fluoroquinolones and three collagen-associated adverse events: aortic aneurysm or aortic dissection, retinal detachment, and tendon disorders. METHODS: We searched PubMed, Embase, and Scopus for observational studies up to January 2019. Cohort and case-control studies were included if they reported data on the risk of collagen-related adverse events associated with fluoroquinolone exposure versus no exposure. We assessed the quality of the included studies using the Newcastle-Ottawa Scale. Effect statistics were pooled using random-effects models. Sensitivity and subgroup analyses were performed to identify any source of heterogeneity. RESULTS: After screening 2729 citations, we included 22 observational studies (12 cohort studies and ten case-control studies) with 19,207,552 participants. Current use of fluoroquinolones was significantly associated with aortic aneurysm and aortic dissection (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.92-2.52), tendon disorders (OR 1.89; 95% CI 1.53-2.33), and retinal detachment (sensitivity analysis, OR 1.25; 95% CI 1.01-1.53). Past fluoroquinolone use (> 30 and ≤ 365 days) was associated with retinal detachment (OR 1.27; 95% CI 1.09-1.47). CONCLUSIONS: Fluoroquinolone use incurs a risk of developing three collagen-associated diseases (aortic aneurysm or aortic dissection, retinal detachment, and tendon disorders). Patients at an increased risk of collagen-associated diseases should not use fluoroquinolones unless no other options are available.

Experimental and Theoretical Investigation of the Effect of Oxygen Vacancies on the Electronic Structure and Pseudocapacitance of MnO2.

Defect engineering is an effective way to modulate the intrinsic physicochemical properties of materials. In this work, δ-MnO2 with oxygen vacancies is fabricated by a simple oxidation or reduction process, and the relationship between the electronic structure and pseudocapacitance is systematically studied through experimental analysis and theoretical calculations. The peaks in the Raman spectra of the as-prepared samples are shifted compared with those of pure MnO2 and the Mn3+ /Mn4+ ratio and O species content also change after the introduction of oxygen vacancies. The optimized samples exhibit a better specific capacitance of 207 F g-1 after the oxidation process and 181.4 F g-1 after the reduction treatment compared with only 143.9 F g-1 for the pure MnO2 . The samples obtained through the oxidation or reduction process also retain 93.3 or 86.4 % of the initial capacity after 5000 cycles. The excellent properties are attributed to the enhanced conductivity and increased surface reactivity or electrochemically active sites. Theoretical calculations demonstrate that the presence of oxygen vacancies leads to an increase in the density of states, which improves the redox reaction of MnO2 . This study will provide a reference for exploring and designing highperformance pseudocapacitive materials.

Melatonin protects circulatory death heart from ischemia/reperfusion injury via the JAK2/STAT3 signalling pathway.

AIMS: The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion. MAIN METHODS: Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3. KEY FINDINGS: Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490. SIGNIFICANCE: Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.

Metformin prescription and aortic aneurysm: systematic review and meta-analysis.

OBJECTIVE: To assess the association of metformin prescription with the risk of aortic aneurysm, aortic aneurysm events and the enlargement of abdominal aortic aneurysm (AAA). DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed, Embase and Scopus for epidemiological studies up to November 2018. We included observational studies which evaluated the association of metformin prescription with the risk of aortic aneurysm disease, and we also included studies involving progression and enlargement of AAA. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Random-effect meta-analyses were conducted in line with the between-study heterogeneity. Sensitivity analyses were performed to identify the source of heterogeneity. RESULTS: Eight studies enrolling 29 587 participants met the inclusion criteria and were included in this systematic review. We found that metformin prescription could significantly limit the enlargement of aortic aneurysm (weighted mean difference: -0.83 mm/year, 95% CI -1.38 to -0.28, I2=89.6%) among patients with AAA. Metformin prescription status may be associated with a decreased risk of aortic aneurysm and aortic aneurysm events. CONCLUSIONS: According to the available epidemiological evidence, metformin prescription could limit the expansion of AAA among patients with this disease, and may be involved with a lower incidence of aortic aneurysm and aortic aneurysm events. Randomised controlled trials are needed to confirm whether metformin could reduce the enlargement of AAA in patients with or without diabetes.

Covalent organic frameworks converted N, B co-doped carbon spheres with excellent lithium ion storage performance at high current density.

Covalent organic frameworks (COFs) with devisable nanostructures have exhibited extensive application prospects in energy storage and conversion. In this work, spherical COFs were successfully utilized as an ideal precursor for N, B co-doped carbon spheres (NBCs) that display hierarchical spherical architectures with rich pores. When applied as lithium ion batteries (LIBs) anode, NBCs exhibit high reversible specific capacity and outstanding long-life cycling stability (205.5 mAh g-1 at 5.0 A g-1 and 171.4 mAh g-1 at 10.0 A g-1 after 5000 cycles) owing to their hierarchical porosity, unique structure and in-situ N, B co-doping. The excellent lithium storage ability, especially satisfactory long cycling stability, enables NBCs to be a promising candidate for LIBs.

Design of Helically Double-Leveled Gaps for Stretchable Fiber Strain Sensor with Ultralow Detection Limit, Broad Sensing Range, and High Repeatability.

Flexible strain sensors have attracted extensive attention in electronic skins and health monitoring systems. To date, it remains a great challenge for the development of a multifunctional strain sensor with simultaneous ultralow detection limit, broad sensing range, and high repeatability. In this paper, we report a new carbon nanotube/flexible fiber-shaped strain sensor. The fiber substrate has a novel microstructure where a highly elastic rubber fiber core is tightly wound by a continuous spring-like polypropylene fiber as the shell. Our sensor offers combined sensing performances of ultralow detection limit of 0.01% strain, wide sensing range of 200% strain, and high repeatability of 20 000 cycles by designing double-leveled helical gaps. This strain sensor shows a rapid response time of 70 ms under both stretching and releasing. In addition, it is available for a variety of other deformations such as bending and torsion. Due to the unique fiber structure, it can extend the torsion detection range to 1000 rad m-1. On the basis of the superior sensing performances, our sensor demonstrates to efficiently work for both subtle physiological activities and vigorous human motions. This work provides a general and effective strategy for designing smart wearable devices with high performance.

Acute Type I aortic dissection: a propensity-matched comparison of elephant trunk and arch debranching repairs.

OBJECTIVES: Our goal was to compare the performance of the frozen elephant trunk (FET) and the hybrid aortic arch debranching procedures for acute Type I aortic dissection. METHODS: From January 2013 to December 2015, 168 patients with Type I aortic disease underwent ascending aorta and total aortic arch replacement with FET implantation (the FET group, n = 132) or arch debranching with 1-stage aortic arch exclusion using an endovascular stent in a retrograde manner (the debranching group, n = 36). A propensity score-matched subgroup of 26 pairs was identified. Perioperative data and mid-term follow-up results were assessed. RESULTS: In the FET and the debranching groups, the 30-day mortality rates were 14.4% and 5.6% (P = 0.254) and the incidence of stroke was 5.3% and 5.6% (P > 0.999). Cardiopulmonary bypass time was significantly shortened, and the circulatory arrest was exempted in the debranching group. Cardiopulmonary bypass time was identified as a predictor for 30-day mortality (P = 0.027, odds ratio 1.01). Body mass index ≥ 25 kg/m2 was associated with multiorgan dysfunction syndrome (P = 0.016, odds ratio 3.51). Surgical modality did not significantly affect early outcomes. The 3-year survival rate was 76.1% (95% confidence interval, 63.0-81.9%) in the FET group and 82.5% (95% confidence interval, 65.2-91.8%) in the debranching group (P = 0.330). CONCLUSIONS: The hybrid aortic arch procedure without circulatory arrest can be safely performed on patients with acute Type I aortic dissection. Irrespective of cost-effectiveness, arch debranching was a promising alternative for patients who were unfit for the FET procedure.

An Ultraflexible Silicon-Oxygen Battery Fiber with High Energy Density.

To satisfy the rapid development of portable and wearable electronics, it is highly desired to make batteries with both high energy densities and flexibility. Although some progress has been made in recent decades, the available batteries share critical problems of poor energy storage capacity and low flexibility. Herein, we have developed a silicon-oxygen battery fiber with high energy density and ultra-high flexibility by designing a coaxial architecture with a lithiated silicon/carbon nanotube hybrid fiber as inner anode, a polymer gel as middle electrolyte and a bare carbon nanotube sheet as outer cathode. The fiber showed a high energy density of 512 Wh kg-1 and could effectively work after bending for 20 000 cycles. These battery fibers have been further woven into flexible textiles for a large-scale application.

Sn-doped TiO2 nanotubes as superior anode materials for sodium ion batteries.

Sn-doped TiO2 nanotubes were employed as anodes for sodium ion batteries. The electrodes exhibit a high maximum charge capacity of 257 mA h g(-1) after 50 cycles at a current density of 50 mA g(-1) with good rate capability and especially excellent cycling stability, mainly due to the increase of electrical conductivity by Sn doping.

Ionic conductivity of ß-cyclodextrin-polyethylene-oxide/alkali-metal-salt complex.

Highly conductive, crystalline, polymer electrolytes, ß-cyclodextrin (ß-CD)-polyethylene oxide (PEO)/LiAsF6 and ß-CD-PEO/NaAsF6 , were prepared through supramolecular self-assembly of PEO, ß-CD, and LiAsF6 /NaAsF6 . The assembled ß-CDs form nanochannels in which the PEO/X(+) (X=Li, Na) complexes are confined. The nanochannels provide a pathway for directional motion of the alkali metal ions and, at the same time, separate the cations and the anions by size exclusion.

Carbon microspheres via microwave-assisted synthesis as counter electrodes of dye-sensitized solar cells.

Carbon microspheres (CSs) were successfully fabricated and used as counter electrodes of dye-sensitized solar cells (DSSCs). CSs were obtained through a fast microwave-assisted approach using sucrose as the precursor in a microwave system and subsequent thermal treatment at 600, 800 and 1000°C. A maximum photovoltaic conversion efficiency of 5.5% is achieved for DSSCs based on the CSs counter electrodes, which is comparable to the cell based on conventional Pt counter electrode at one sun (AM 1.5 G, 100 mW cm(-2)). The results suggest the CSs to be a potential candidate for counter electrodes of DSSCs.

Porous nitrogen-doped carbon microspheres as anode materials for lithium ion batteries.

Nitrogen-doped carbon microspheres (NCSs) were fabricated via a simple, fast and energy-saving microwave-assisted method followed by thermal treatment under an ammonia atmosphere. NCSs thermally treated at different temperatures were investigated as anode materials for lithium ion batteries (LIBs). The results show that NCSs treated at 900 °C exhibit a maximum reversible capacity of 816 mA h g(-1) at a current density of 50 mA g(-1) and preserve a capacity of 660 mA h g(-1) after 50 cycles, and even at a high current density of 1000 mA g(-1), a capacity of 255 mA h g(-1) is maintained. The excellent electrochemical performance of NCSs is due to their porous structure and nitrogen-doping. The present NCSs should be promising low-cost anode materials with a high capacity and good cycle stability for LIBs.