High-temperature superconductivities and crucial factors influencing the stability of LaThH12 under moderate pressures.

The recent discovery of high-temperature superconductivity in compressed hydrides has reignited the long-standing quest for room-temperature superconductors. However, the synthesis of superconducting hydrides under moderate pressure and the identification of crucial factors that affect their stability remain challenges. Here, we predicted the ternary clathrate phases of LaThH12 with potential superconductivity under high pressures and specifically proposed a novel R3̄c-LaThH12 phase exhibiting a remarkable Tc of 54.95 K at only 30 GPa to address these confusions. Our first-principles studies show that the high-Tc value of Pm3̄m and Cmmm-LaThH12 phases was induced by the strong electron-phonon coupling driven by the synergy of the electron-phonon matrix element and phonon softening caused by Fermi surface nesting. Importantly, we demonstrate the dual effects of enhanced ionic bonding and expanded orbital hybridization between Th-6f and H-sp3 orbitals during depressurization are primary factors governing the dynamic stability of R3̄c-LaThH12 at low pressures. Our findings offer crucial insights into the underlying mechanisms governing low-pressure stability and provide guidance for experimental efforts aimed at realizing hydrogen-based superconductors with both low synthesis pressures and high-Tc.

Hollow Crystallization COF Capsuled MOF Hybrids Depict Serum Metabolic Profiling for Precise Early Diagnosis and Risk Stratification of Acute Coronary Syndrome.

Acute coronary syndrome (ACS), comprising unstable angina (UA) and acute myocardial infarction (AMI), is the leading cause of death worldwide. Currently, lacking effective strategies for classifying ACS hinders the prognosis improvement of ACS patients. Disclosing the nature of metabolic disorders holds the potential to reflect disease progress and high-throughput mass spectrometry-based metabolic analysis is a promising tool for large-scale screening. Herein, a hollow crystallization COF capsuled MOF hybrids (UiO-66@HCOF) assisted serum metabolic analysis is developed for the early diagnosis and risk stratification of ACS. UiO-66@HCOF exhibits unrivaled chemical and structural stability as well as endowing satisfying desorption/ionization efficiency in the detection of metabolites. Paired with machine learning algorithms, early diagnosis of ACS is achieved with the area under the curve (AUC) value of 0.945 for validation sets. Besides, a comprehensive ACS risk stratification method is established, and the AUC value for the discrimination of ACS from healthy controls, and AMI from UA are 0.890, and 0.928. Moreover, the AUC value of the subtyping of AMI is 0.964. Finally, the potential biomarkers exhibit high sensitivity and specificity. This study makes metabolic molecular diagnosis a reality and provided new insight into the progress of ACS.

New insights into the effect of VMP1 on the treatment of pressure overload-induced pathological cardiac hypertrophy: Involving SERCA-regulated autophagic flux.

Pathological cardiac hypertrophy is an adaptive reaction in response to pressure or volume overload. Autophagy is critical for damage caused by pathological cardiac hypertrophy. Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that is effective in activating autophagy. However, the role of VMP1 in pathological cardiac hypertrophy and its underlying mechanisms remain elusive. This study was designed to explore the potential mechanisms of VMP1 on pressure overload-induced pathological cardiac hypertrophy. In this work, abdominal aorta constriction (AAC) surgery was used to induce pathological cardiac hypertrophy in male C57BL/6 mice. H9C2 cardiomyocytes were treated with phenylephrine stimulation (PE) to induce the hypertrophic response. The in vivo results revealed that mice with AAC surgery caused pathological cardiac hypertrophy as evidenced by improved cardiac function according to multiple echocardiographic parameters. Moreover, elevated VMP1 expression was also observed in mice after AAC surgery. VMP1 knockdown aggravated changes in cardiac structure, cardiac dysfunction, and fibrosis. Meanwhile, VMP1 knockdown suppressed autophagy and endoplasmic reticulum calcium ATPase (SERCA) activity in heart tissues. H9C2 cardiomyocytes with VMP1 overexpression were used to investigate the specific mechanism of VMP1 in pathological cardiac hypertrophy, and VMP1 overexpression increased autophagic flux by upregulating SERCA activity. In conclusion, these findings revealed that VMP1 protected against pressure overload-induced pathological cardiac hypertrophy by inducing SERCA-regulated autophagic flux. Our results provide valuable insights regarding the pathophysiology of pathological cardiac hypertrophy and clues to a novel target for the treatment of pathological cardiac hypertrophy.

Real-time 3D echocardiographic transilluminated imaging combined with artificially intelligent left atrial appendage measurement for atrial fibrillation interventional procedures.

Aims: This study investigated the feasibility and accuracy of real-time three-dimensional (3D) echocardiographic transilluminated imaging (TrueVue Glass) in left atrial appendage (LAA) anatomical morphology and artificial intelligence (AI)-assisted 3D automated LAA measurement (3D Auto LAA) software in the preoperative evaluation of LAA occlusion (LAAO) in patients with atrial fibrillation (AF). Method and results: Thirty-seven patients with AF were selected. Two-dimensional (2D) and real-time 3D transesophageal echocardiography (RT3D-TEE) were performed preoperatively, using conventional 3D, the new 3D TrueVue Glass mode, and cardiac computed tomography angiography (CCTA) to assess and type the morphology of LAA. Physiological parameters were measured using traditional 2D and 3D manual (3D Manual LAA), 3D Auto LAA, and CCTA. TrueVue Glass for LAA outer contour display was compared with CCTA. Comparisons were based on correlation and consistency in measuring the maximum diameter (LZ max), minimum diameter (LZ min), area (LZ area), and circumference (LZ cir) of LAA landing zone (LZ). Times and variabilities were compared. The concordance rate for external shape of LAA was 97.14% between TrueVue Glass and CCTA. 3D Auto LAA and 3D Manual LAA have a stronger correlation and higher consistency in all parameters. 3D Auto LAA showed higher intra- and interobserver reproducibility and allowed quicker analysis (p < 0.05). LAAO was performed in 35 patients (94.59%), and none of which had serious adverse events. Conclusion: TrueVue Glass is the first non-invasive and radiation-free visualization of the overall external contour of LAA and its adjacent structures. 3D Auto LAA simplifies the measurement, making the preoperative assessment more efficient and convenient while ensuring the accuracy and reproducibility. A combination of the two is feasible for accurate and rapid assessment of LAA anatomy and physiology in AF patients and has practical application in LAAO.

Covalent three-dimensional carbon nanotube and derived B-C-N polymorphs with superhardness and zero Poisson's ratio.

Carbon is one of the most versatile atoms and fosters a wealth of carbon allotropes with superior mechanical and electronic properties. A three-dimensional covalent carbon nanotube, named CCN, with a hexagonal honeycomb-like crystalline structure is proposed theoretically. CCN consists of sp 3 bonded coaxially teamed (6,0) carbon nanotubes, and the tube walls possess intrinsic wrinkles, which trigger miraculous physical properties. The mechanical and thermal dynamic stabilities are confirmed, and molecular dynamics simulations indicate high temperature thermal stability up to 1500 K. CCN has an unusual cork-like zero Poisson's ratio along the axial direction of the nanotubes, and the axial/radial stretching or compression rarely effects the radial/axial dimensions of the nanotubes. CCN is superhard with Vickers hardness of 82.8 GPa, matching that of cubic boron nitride. Substitution B and N atoms for C atoms result in superhard CCN-B12N8 and CCN-C8N12 with quasi-zero Poisson's radio along both axial and radial directions.

Systematic review of efficacy of direct oral anticoagulants and vitamin K antagonists in left ventricular thrombus.

AIMS: Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed. CONCLUSIONS: Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

Extreme mechanical anisotropy in diamond with preferentially oriented nanotwin bundles.

Mechanical properties of covalent materials can be greatly enhanced with strategy of nanostructuring. For example, the nanotwinned diamond with an isotropic microstructure of interweaved nanotwins and interlocked nanograins shows unprecedented isotropic mechanical properties. How the anisotropic microstructure would impact on the mechanical properties of diamond has not been fully investigated. Here, we report the synthesis of diamond from superaligned multiwalled carbon nanotube films under high pressure and high temperature. Structural characterization reveals preferentially oriented diamond nanotwin bundles with an average twin thickness of ca. 2.9 nm, inherited from the directional nanotubes. This diamond exhibits extreme mechanical anisotropy correlated with its microstructure (e.g., the average Knoop hardness values measured with the major axis of the indenter perpendicular and parallel to nanotwin bundles are 233 ± 8 and 129 ± 9 GPa, respectively). Molecular dynamics simulation reveals that, in the direction perpendicular to the nanotwin bundles, the dense twin boundaries significantly hinder the motion of dislocations under indentation, while such a resistance is much weaker in the direction along the nanotwin bundles. Current work verifies the hardening effect in diamond via nanostructuring. In addition, the mechanical properties can be further tuned (anisotropy) with microstructure design and modification.

Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis.

BACKGROUND: The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. METHODS: We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel-Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. RESULTS: Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case-control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11-1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84-2.47, P = 0.001, I2 = 66.4%). CONCLUSIONS: The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.

Serum amyloid A1 can be a novel biomarker for evaluating the presence and severity of acute coronary syndrome.

BACKGROUND: Serum amyloid A (SAA) is an acute phase protein and a novel inflammatory biomarker of cardiovascular diseases. Of the four subtypes, SAA1 is the most representative biomarker. In this study, we aimed to assess the value of SAA1 as a novel biomarker for evaluating the presence and severity of acute coronary syndrome (ACS) in Chinese patients. METHODS AND RESULTS: A total of 140 ACS patients and 88 non-ACS patients (including 36 stable coronary artery disease (SCAD) patients and 52 healthy controls) who underwent coronary angiography were enrolled. The SAA1 level was significantly higher in ACS patients compared with the SCAD and healthy control subgroups (P < 0.001, respectively), and was significantly higher in the high SYNTAX Score II (SS II) group compared with the medium SS II group and low SS II group (P < 0.001, respectively) in ACS patients. The cutoff level of SAA1 for indicating the presence of ACS was 324.65 ng/mL (sensitivity of 77.9%, specificity of 60.2% and an area under the curve of 0.717). The increased SAA1 levels were positively associated with the presence (OR = 1.013, P < 0.001) and severity (OR = 1.023, P < 0.001) of ACS. Furthermore, there was a positive correlation between SAA1 levels and SS II (r = 0.467, P < 0.001). CONCLUSIONS: Our results suggest that elevated SAA1 levels may be a novel biomarker for evaluating the presence of ACS and the severity of CAD in ACS patients. Measuring SAA1 levels makes it possible to evaluate the presence of ACS and severity of CAD in ACS patients.

Characterization of differentially expressed plasma proteins in patients with acute myocardial infarction.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Novel biomarkers are needed to identify NSTEMI in AMI patients. The study objective was to use proteomics to identify novel plasma biomarkers for STEMI and NSTEMI patients. iTRAQ analysis was performed on pooled samples from 8 healthy controls and 12 STEMI and 12 NSTEMI patients. Bioinformatics analysis identified 95 differentially expressed proteins that were differentially expressed in the plasma of AMI patients and healthy controls; 28 of these proteins were found in STEMI/Con (22 upregulated and 6 downregulated), 48 in NSTEMI/Con (12 upregulated and 36 downregulated), and 44 in NSTEMI/STEMI (11 upregulated and 33 downregulated). Protein network analysis was then performed using STRING software. Functional analysis revealed that the identified plasma proteins were mainly involved with carbon metabolism, toll-like receptor signaling pathway, and hypertrophic cardiomyopathy. Nine of the proteins (SSA1, MDH1, FCN2, GPI, S100A8, LBP, vinculin, VDBP, and RBP4) that changed levels during AMI progression were further validated by ELISA. The constructed plasma proteome could reflect the AMI pathogenesis molecular mechanisms and provide a method for the early identification of NSTEMI in AMI patients. SIGNIFICANCE: The aim of this study was to use proteomics to identify novel predictive plasma biomarkers for patients with acute myocardial infarction (AMI), which would allow for either identification of individuals at risk of an infarction, and early identification of NSTEMI in patients with AMI. Using an approach that combined iTRAQ with LC-MS/MS, we found 95 proteins that showed significant differences in expression levels among the AMI patients and healthy controls. The proteins SSA1, MDH1, FCN2, GPI, S100A8, LBP, vinculin, VDBP, and RBP4 were found to play crucial roles in the pathogenesis of AMI. Using bioinformatics analysis, we found that dysregulation of carbon metabolism, toll-like receptor signaling pathway, and hypertrophic cardiomyopathy may be the major driving forces for cardiac damage during myocardial infarction. However, further investigations are needed to verify the mechanisms involved in the development of AMI especially NSTEMI. Taken together, our findings lay the foundation for understanding the molecular mechanisms underlying the pathogenic processes of AMI, and suggest potential applications for specific biomarkers in early diagnosis and determination of prognosis.

Approaching the voltage and energy density limits of potassium-selenium battery chemistry in a concentrated ether-based electrolyte.

Potassium-selenium (K-Se) batteries offer fairly high theoretical voltage (∼1.88 V) and energy density (∼1275 W h kgSe -1). However, in practice, their operation voltage is so far limited to ∼1.4 V, resulting in insufficient energy utilization and mechanistic understanding. Here, it is demonstrated for the first time that K-Se batteries operating in concentrated ether-based electrolytes follow distinctive reaction pathways involving reversible stepwise conversion reactions from Se to K2Se x (x = 5, 3, 2, 1). The presence of redox intermediates K2Se5 at ∼2.3 V and K2Se3 at ∼2.1 V, in contrast with previous reports, enables record-high average discharge plateau voltage (1.85 V) and energy density (998 W h kgSe -1 or 502 W h kgK2Se -1), both approaching the theoretical limits and surpassing those of previously reported Na/K/Al-Se batteries. Moreover, experimental analysis and first-principles calculations reveal that the effective suppression of detrimental polyselenide dissolution/shuttling in concentrated electrolytes, together with high electron conductibility of Se/K2Se x , enables fast reaction kinetics, efficient utilization of Se, and long-term cyclability of up to 350 cycles, which are impracticable in either K-S counterparts or K-Se batteries with low/moderate-concentration electrolytes. This work may pave the way for mechanistic understanding and full energy utilization of K-Se battery chemistry.

Safe, Low-Cost, Fast-Kinetics and Low-Strain Inorganic-Open-Framework Anode for Potassium-Ion Batteries.

A key challenge for potassium-ion batteries is to explore low-cost electrode materials that allow fast and reversible insertion of large-ionic-size K+ . Here, we report an inorganic-open-framework anode (KTiOPO4 ), which achieves a reversible capacity of up to 102 mAh g-1 (307 mAh cm-3 ), flat voltage plateaus at a safe average potential of 0.82 V (vs. K/K+ ), a long lifespan of over 200 cycles, and K+ -transport kinetics ≈10 times faster than those of Na-superionic conductors. Combined experimental analysis and first-principles calculations reveal a charge storage mechanism involving biphasic and solid solution reactions and a cell volume change (9.5 %) even smaller than that for Li+ -insertion into graphite (≈10 %). KTiOPO4 exhibits quasi-3D lattice expansion on K+ intercalation, enabling the disintegration of small lattice strain and thus high structural stability. The inorganic open-frameworks may open a new avenue for exploring low-cost, stable and fast-kinetic battery chemistry.

Highly reversible potassium-ion intercalation in tungsten disulfide.

Rechargeable potassium-ion batteries (PIBs) show promise beyond Li-ion technology in large-scale electrical-energy storage due to the abundance and low cost of potassium resources. However, the intercalation of large-size K+ generally results in irreversible structural degradation and short lifespan to the hosts, representing a major obstacle. Here, we report a new electrochemical K+-intercalation host, tungsten disulfide (WS2), which can store 0.62 K+ per formula unit with a reversible capacity of 67 mA h g-1 and well-defined voltage plateaus at an intrinsically safe average operation potential of 0.72 V versus K/K+. In situ X-ray diffraction and ex situ electron microscopy revealed the underlying intercalation mechanism, a relatively small cell volume change (37.81%), and high reversibility of this new battery chemistry. Such characteristics impart WS2 with ultrahigh structural stability and a long lifespan, regardless of deep or fast charging. WS2 achieved record-high cyclability among chalcogenides up to 600 cycles with 89.2% capacity retention at 0.3C, and over 1000 cycles with 96.3% capacity retention and an extraordinary average Coulombic efficiency of 99.90% at 2.2C. This intercalation electrochemistry may open up new opportunities for the design of long-cycle-life and high-safety PIBs.

Metformin regulates atrial SK2 and SK3 expression through inhibiting the PKC/ERK signaling pathway in type 2 diabetic rats.

BACKGROUND: Our previous study showed that metformin regulates the mRNA and protein levels of type 2 small conductance calcium-activated potassium channel (SK2) and type 3 small conductance calcium-activated potassium channels (SK3) in atrial tissue as well as the ion current of atrial myocytes in rats with type 2 diabetes mellitus (T2DM), but the underlying signaling mechanism is unknown. This study aimed to investigate whether metformin regulates atrial SK2 and SK3 protein expression in T2DM rats though the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: A T2DM rat model was established using a high-fat and high-sugar diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into the following five groups: the control group, the untreated T2DM group, the metformin-treated only group, the phorbol 12-myristate 13-acetate (PMA; a PKC agonist administered by intraperitoneal injection) treatment group, and the recombinant human epidermal growth factor (rh-EGF; an ERK agonist administered by tail vein injection) treatment group. The activity of PKC in atrial tissues was assayed by a PKC kinase activity assay kit. The protein expression of SK2, SK3, and phosphorylated ERK (pERK) were determined by western blotting and immunohistochemistry. RESULTS: Compared with the Control group, atrial PKC activity and pERK and SK3 protein expression were increased, while SK2 protein expression was decreased in atrial tissues of T2DM rats. Eight weeks of metformin treatment inhibited the PKC activity and pERK and SK3 expression, and elevated SK2 expression compared with the T2DM group. Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression. In addition, the injection with PMA significantly elevated the expression of pERK. CONCLUSIONS: The PKC/ERK signaling pathway is involved in the downregulation of SK2 expression and the upregulation of SK3 expression in the atrium of T2DM rats. Long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway.

Metformin Regulates the Expression of SK2 and SK3 in the Atria of Rats With Type 2 Diabetes Mellitus Through the NOX4/p38MAPK Signaling Pathway.

We previously found that metformin regulates the ion current conducted by the small conductance calcium-activated potassium channels (SK channels) in the atria of rats with type 2 diabetes mellitus (T2DM) as well as the mRNA and protein expression of the SK2 and SK3 subtypes of SK channels. In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM. We randomly divided Wistar rats into the control group, the untreated T2DM group, the metformin-treated group, the group receiving subcutaneous injections of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor diphenyleneiodonium (DPI), and the group receiving tail vein injections of the p38MAPK agonist anisomycin. Real-time polymerase chain reaction, Western blot, and immunohistochemistry were applied to examine the expression levels of SK2, SK3, NOX4, and phospho-p38MAPK (p-p38MAPK) mRNAs and proteins in the atrial tissue of relevant groups. We observed that the expression levels of NOX4 mRNA and protein and p-p38MAPK protein were significantly elevated in the atria of rats with T2DM compared with the control group. In addition, SK2 protein expression was reduced, whereas SK3 protein expression was increased. The 8-week treatment with metformin markedly reduced the expression levels of NOX4 mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and downregulated the SK3 expression. Tail vein injection with anisomycin significantly increased the p-p38MAPK expression while further inhibiting the expression of SK2 and enhancing the expression of SK3. Subcutaneous injection with DPI considerably inhibited the expression of NOX4, further enhanced the expression of SK2 and suppressed the expression of SK3. In addition, subcutaneous injection with DPI significantly suppressed the phosphorylation of p38MAPK. In conclusion, the NOX4/p38MAPK signaling pathway mediates the downregulation of SK2 and the upregulation of SK3 in the atria of rats with T2DM. Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.

Novel carbon polymorphs with cumulative double bonds in three-dimensional sp-sp2 hybrid framework.

A conspicuous amount of theoretical study has been published on the properties of carbon allotropes with alternate single and triple bonds, (-C[triple bond, length as m-dash]C-)n. However, theoretical characterizations of carbon allotropes with cumulative double bonds ([double bond, length as m-dash]C[double bond, length as m-dash]C[double bond, length as m-dash])n is almost non-existent in literature. Based upon first-principles calculations, two new three-dimensional (3D) microporous carbon allotropes consisting of whorl chains connected by cumulative double bonds in a sp-sp2 hybrid framework have been proposed in this study. One of these structures, namely, Trig-C9 was obtained by an evolutionary particle swarm structural search, while the other structure, denoted as Trig-C15, was obtained by inserting double bonds into Trig-C9. Both the 3D sp-sp2 hybridized carbons have a trigonal structure with 9 and 15 atoms in the hexagonal primitive cells. The calculated results demonstrate that these polymorphs are thermodynamically, mechanically, and dynamically feasible. Trig-C9 and Trig-C15 are indirect semiconductors with band gaps of 2.70 eV and 1.25 eV, respectively. Their unique frameworks render them mechanical ductility and significant elastic anisotropy. These results open up new horizons for the exploration of new carbon phases with unique structural, mechanical, and electronic properties.

Metformin restores electrophysiology of small conductance calcium-activated potassium channels in the atrium of GK diabetic rats.

BACKGROUND: Small conductance calcium-activated potassium channels (SK channels) play a critical role in action potential repolarization in cardiomyocytes. Recently, the potential anti-arrhythmic effect of metformin in diabetic patients has been recognized, yet the underlying mechanism remains elusive. METHODS: Diabetic Goto-Kakizaki (GK) rats were untreated or treated with metformin (300 mg/kg/day) for 12 weeks, and age-matched Wistar rats were used as control (n = 6 per group). Electrocardiography, Hematoxylin-eosin staining and Masson's trichome staining were performed to assess cardiac function, histology and fibrosis. The expression levels of the SK channels in the myocardium were determined by real-time PCR and Western blotting. The electrophysiology of the SK channels in the cardiomyocytes isolated from the three groups of rats was examined by patch clamp assay, with specific blockade of the SK channels with apamin. RESULTS: Metformin treatment significantly reduced cardiac fibrosis and alleviated arrhythmia in the diabetic rats. In the atrial myocytes from control, GK and metformin-treated GK rats, the expression of KCa2.2 (SK2 channel) was down-regulated and the expression of KCa2.3 (SK3 channel) was up-regulated in the atrium of GK rats as compared with that of control rats, and metformin reversed diabetes-induced alterations in atrial SK channel expression. Moreover, patch clamp assay revealed that the SK current was markedly reduced and the action potential duration was prolonged in GK atrial myocytes, and the SK channel function was partially restored in the atrial myocytes from metformin-treated GK rats. CONCLUSIONS: Our data suggests an involvement of the SK channels in the development of arrhythmia under diabetic conditions, and supports a potential beneficial effect of metformin on atrial electrophysiology.

Type 2 Diabetes Induces Prolonged P-wave Duration without Left Atrial Enlargement.

Prolonged P-wave duration has been observed in diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to elucidate the possible mechanisms. A rat model of type 2 diabetes mellitus (T2DM) was used. P-wave durations were obtained using surface electrocardiography and sizes of the left atrium were determined using echocardiography. Cardiac inward rectifier K(+) currents (Ik1), Na(+) currents (INa), and action potentials were recorded from isolated left atrial myocytes using patch clamp techniques. Left atrial tissue specimens were analyzed for total connexin-40 (Cx40) and connexin-43 (Cx43) expression levels on western-blots. Specimens were also analyzed for Cx40 and Cx43 distribution and interstitial fibrosis by immunofluorescent and Masson trichrome staining, respectively. The mean P-wave duration was longer in T2DM rats than in controls; however, the mean left atrial sizes of each group of rats were similar. The densities of Ik1 and INa were unchanged in T2DM rats compared to controls. The action potential duration was longer in T2DM rats, but there was no significant difference in resting membrane potential or action potential amplitude compared to controls. The expression level of Cx40 protein was significantly lower, but Cx43 was unaltered in T2DM rats. However, immunofluorescent labeling of Cx43 showed a significantly enhanced lateralization. Staining showed interstitial fibrosis was greater in T2DM atrial tissue. Prolonged P-wave duration is not dependent on the left atrial size in rats with T2DM. Dysregulation of Cx40 and Cx43 protein expression, as well as fibrosis, might partly account for the prolongation of P-wave duration in T2DM.

Rosuvastatin Alleviates Type 2 Diabetic Atrial Structural and Calcium Channel Remodeling.

Recent evidence has indicated that type 2 diabetes mellitus is related to an increased risk of atrial arrhythmias, which might result from atrial structural and electrical remodeling. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), known as lipid-lowering agents, have been shown to exert antiarrhythmic effects both in experimental models and in humans. In this study, we postulate that atrial structural and calcium channel remodeling may occur in streptozotocin-induced type 2 diabetic rats and can be alleviated by rosuvastatin (RSV) therapy. We randomly divided Wistar rats into control, untreated diabetic, RSV-treated control, and RSV-treated diabetic animals. After treatment with RSV for 4 weeks, rats were assessed by metabolic tests, histopathology, and transmission electron microscopy. The expression of Cav1.2, Cav3.1, and Cav3.2 in atrial tissues was detected by real-time reverse transcriptase polymerase chain reaction and Western blot, and inward calcium currents (l(Ca-L) and l(Ca-T)) were recorded in isolated atrial myocytes using patch-clamp techniques. Compared with controls, diabetic rats displayed severe metabolic disorders and a disorganized cellular ultrastructure. In diabetic rats, the expression of Cav1.2 mRNA and protein was significantly decreased, whereas that of Cav3.1 was significantly increased. Long-term RSV treatment partially relieved some pathological changes in diabetic rats. However, Cav3.2 mRNA and protein remained unchanged in control and diabetic groups and was unaffected by RSV. Diabetic atrial myocytes showed significantly reduced L-type but increased T-type, Ca (2+) currents, and this effect was significantly reversed by RSV. In conclusion, long-term RSV therapy can alleviate structural and calcium channel remodeling in the type 2 diabetic rat atrium.

Efficacy of high-dose rosuvastatin preloading in patients undergoing percutaneous coronary intervention: a meta-analysis of fourteen randomized controlled trials.

BACKGROUND: Numerous studies have evidenced that statins can reduce the incidence of cardiovascular disease. However, the effects of high-dose rosuvastatin (RSV) preloading in patients undergoing percutaneous coronary intervention (PCI) are controversial. OBJECTIVE: We attempted to identify and quantify the potential cardioprotective benefits of high-dose RSV preloading on final thrombolysis in myocardial infarction (TIMI) flow grade, major adverse cardiac events (MACE), and peri-procedural myocardial injury (PMI) in patients undergoing PCI. METHODS: Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ISI Web of Science databases were systematically searched for randomized controlled trials (RCTs) up to June 2015. We assessed the incidence of MACE and PMI in all enrolled patients for subgroups stratified by clinical presentation and previous statin therapy during the follow-up period. RESULTS: Fourteen trials with 3368 individuals were included in our meta-analysis. High-dose RSV preloading before PCI lead to a 58 % reduction in MACE (odds ratio [OR] = 0.42, 95 % confidence intervals [CI]: 0.29-0.61, P < 0.00001) and a 60 % reduction in PMI (OR = 0.40, 95 % CI: 0.25-0.63, P < 0.0001). This procedure also improved the final TIMI flow grade in patients undergoing PCI (OR = 1.61, 95 % CI: 1.09-2.38, P = 0.02). The benefits on MACE were significant for both stable angina patients (OR = 0.42, 95 % CI: 0.21-0.87, P = 0.02) and acute coronary syndrome (ACS) patients (OR = 0.42, 95 % CI: 0.27-0.65, P < 0.0001); and for both statin naïve patients (OR = 0.42, 95 % CI: 0.28-0.64, P < 0.0001) and previous statin therapy patients (OR = 0.28, 95 % CI: 0.10-0.73, P = 0.01). CONCLUSION: High-dose RSV preloading can significantly improve myocardial perfusion and reduce both MACE and PMI in patients undergoing PCI. The cardioprotective benefits of RSV preloading were significant in not only stable angina and ACS patients but also statin naïve and previous statin therapy patients. The cardioprotective benefits of RSV preloading in the follow-up period mainly resulted from a reduction in spontaneous MI and TVR, especially for ACS and statin naïve patients.