Disorder enhanced dynamical heterogeneity in strain glass alloys.

An open question related to strain-glass (STG) alloys is whether they process similar dynamical behaviors to other glass systems. In the present work, we investigate the reorientation process of martensite domains in both STG and martensitic alloys. Our results show the presence of highly doped point defects can greatly intensify the dynamical heterogeneity and spatiotemporal correlation in ferroelastic or shape memory alloy systems, which are also two main hallmarks of structural glasses. What's more, we find that such dynamic heterogeneity exists in a different range spanning microscopic to mesoscopic scales, indicated by our molecular dynamic simulations and time-dependent Ginzburg-Landau modeling. Dopant atoms induced transient strain networks, i.e. spatial correlated local lattice distortion, is a response for such heterogeneous dynamics. The present study thus solidifies STG as a new state of matter and may provide guidelines for developing new STG alloys.

RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission.

OBJECTIVE: Cardiac dysfunction and remodeling are serious complications of sepsis and are the main causes of death in sepsis. RCAN1 is a feedback regulator of cardiac hypertrophy. Here, we aim to investigate the role of RCAN1 in septic cardiomyopathy. METHODS: Mice were randomly divided into control-WT, control-RCAN1-/-, LPS-induced WT and LPS-induced RCAN1-/- groups, some with Midiv-1 or KN93 treatment. The protein levels of RCAN1, p-ERK1/2, NFAT3, Drp1, p-Drp1, p-CaMKII in mouse hearts or cultured cardiomyocytes were determined by Western blotting. Myocardial function was assessed by echocardiography. Cardiac hypertrophy and fibrosis were detected by H&E and Masson's trichrome staining. Mitochondrial morphology was examined by transmission electron microscope. Serum level of LDH was detected by ELISA. RESULTS: Our data show that RCAN1 was downregulated in septic mouse heart and LPS-induced cardiomyocytes. RCAN1-/- mice showed a severe impairment of cardiac function, and increased myocardial hypertrophy and fibrosis. The protein levels of NFAT3 and p-ERK1/2 were significantly increased in the heart tissues of RCAN1-/- mice. Further, RCAN1 deficiency aggravated sepsis-induced cardiac mitochondrial injury as indicated by increased ROS production, pathological fission and the loss of mitochondrial membrane potential. Inhibition of fission with Mdivi-1 reversed LPS-induced cardiac hypertrophy, fibrosis and dysfunction in RCAN1-/- mice. Moreover, RCAN1 depletion promoted mitochondrial translocation of CaMKII, which enhanced fission and septic hypertrophy, while inhibition of CaMKII with KN93 reduced excessive fission, improved LPS-mediated cardiac remodeling and dysfunction in RCAN1-/- mice. CONCLUSIONS: Our finding demonstrated that RCAN1 deficiency aggravated mitochondrial injury and septic cardiomyopathy through activating CaMKII. RCAN1 serves as a novel therapeutic target for treatment of sepsis-related cardiac remodeling and dysfunction.

1-(4-Hydroxyphenyl)-2H-tetrazole-5-thione as a leveler for acid copper electroplating of microvia.

Microvia filling by copper electroplating was performed using plating solution with 1-(4-hydroxyphenyl)-2H-tetrazole-5-thione (HPTT) as the leveler. Galvanostatic Measurements (GMs), Linear Sweep Voltammetry (LSV) and Electrochemical Impedance Spectroscopy (EIS) tests were carried out to investigate the electrochemical behaviors of HPTT and its synergistic effect with other additives, in comparison with 1-phenyltetrazole-5-thione (PMT). GMs showed a convection-dependent interaction between PEP and HPTT. LSV and EIS tests indicated both HPTT and PMT enhanced the inhibition effect of PEP, and the synergistic effect of HPTT and PEP was stronger than that of PMT. Cross-section images illustrated the filling rate of the microvia with a 150 µm diameter and a 75 µm depth was 95.6% in 60 minutes with HPTT as the leveler. Frontier Molecular Orbitals (FMO) and Electrostatic Potential (ESP) of HPTT and PMT using quantum chemical calculations predicted the reaction sites for electrophilic and nucleophilic attack. Quantum chemical calculations suggested that HPTT is easier than PMT to bond to a copper surface and PEP.

Boson-peak-like anomaly caused by transverse phonon softening in strain glass.

Strain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.

Nanoscale bubble domains with polar topologies in bulk ferroelectrics.

Multitudinous topological configurations spawn oases of many physical properties and phenomena in condensed-matter physics. Nano-sized ferroelectric bubble domains with various polar topologies (e.g., vortices, skyrmions) achieved in ferroelectric films present great potential for valuable physical properties. However, experimentally manipulating bubble domains has remained elusive especially in the bulk form. Here, in any bulk material, we achieve self-confined bubble domains with multiple polar topologies in bulk Bi0.5Na0.5TiO3 ferroelectrics, especially skyrmions, as validated by direct Z-contrast imaging. This phenomenon is driven by the interplay of bulk, elastic and electrostatic energies of coexisting modulated phases with strong and weak spontaneous polarizations. We demonstrate reversable and tip-voltage magnitude/time-dependent donut-like domain morphology evolution towards continuously and reversibly modulated high-density nonvolatile ferroelectric memories.

Activation of GPR30 with G1 inhibits oscillatory shear stress-induced adhesion of THP-1 monocytes to HAECs by increasing KLF2.

Atherosclerosis is a chronic inflammatory disease known to be mediated by numerous factors, among which endothelial dysfunction plays a critical role. Oscillatory shear stress induces endothelial cells to lose their anti-atherosclerotic properties and downregulates the expression of the innate protective transcription factor, Krüppel-like factor 2 (KLF2), which is typically upregulated in vascular endothelial cells in response to harmful stimuli. Oxidative stress and inflammation impair endothelial function and damage their survival. Oscillatory shear stress also promotes generation of reactive oxygen species and production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thereby further promoting endothelial dysfunction and formation of atherosclerotic plaque. A major event in the development of atherosclerotic plaque is rolling and adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules including vascular cellular adhesion molecule 1 and endothelial-selectin. Expression of these molecules is also upregulated by oscillatory shear stress. Estrogen has long been recognized as a protective agent against atherosclerosis, but the mechanisms through which estrogen receptors prevent atherogenesis remain unclear. In the present study, we investigated the role of the G-coupled protein estrogen receptor (GPR30) in oscillatory shear stress- induced endothelial dysfunction. We show that agonism of GPR30 by its specific agonist G1 prevented oscillatory shear stress -induced oxidative stress markers and production of inflammatory cytokines and adhesion molecules. As a result, GPR30 activation suppresses monocytes adhesion to endothelial cells. Furthermore, we demonstrate that GPR30 prevents oscillatory shear stress- induced downregulation of KLF2 via ERK5 pathway. These findings suggest that endothelial GPR30 is potential target to suppress oscillatory shear stress mediated atherogenesis.

Prognostic value of cystatin C in patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Circulating cystatin C has been considered as an independent predictor of cardiovascular and all-cause mortality in the general population. The purpose of this study was to evaluate the prognostic value of baseline circulating cystatin C levels in patients with acute coronary syndrome (ACS) through meta-analysis. METHODS: Prospective studies about the relationship between the level of cystatin C and the prognosis of ACS patients were searched on PubMed, Web of science, Cochrane Library and Embase databases from the establishment of the databases to July 2020. The prognostic values included in this analysis covered all-cause mortality, major adverse cardiovascular events (MACE) and recurrent myocardial infarction. The effect index between cystatin C level and ACS risk was carried out by hazard ratio (HR). Stata 15.0 software was used for statistical analysis. The quality of the included literature was evaluated according to Newcastle-Ottawa Scale (NOS). RESULTS: A total of 10 studies were included in this meta-analysis. The results showed that high cystatin C levels significantly predicted the all-cause mortality of ACS, HR = 2.53 (95%CI: 1.72 ~ 3.72). High cystatin C level significantly predicted MACE of patients with ACS, HR = 3.24 (95%CI: 1.30 ~ 8.07). However, it had no significant predictive significance for recurrent myocardial infarction, HR = 1.71 (95%CI:0.99 ~ 2.97). CONCLUSION: Our meta-analysis showed that high cystatin C levels were significantly associated with the death risk and MACE in ACS patients. Therefore, cystatin C can be included in the risk stratification model to guide the treatment of high-risk ACS patients.

Dietary methionine restriction attenuates renal ischaemia/reperfusion-induced myocardial injury by activating the CSE/H2S/ERS pathway in diabetic mice.

Methionine restrictive diet may alleviate ischaemia/reperfusion (I/R)-induced myocardial injury, but its underlying mechanism remains unclear. HE staining was performed to evaluate the myocardial injury caused by I/R and the effect of methionine-restricted diet (MRD) in I/R mice. IHC and Western blot were carried out to analyse the expression of CSE, CHOP and active caspase3 in I/R mice and hypoxia/reoxygenation (H/R) cells. TUNEL assay and flow cytometry were used to assess the apoptotic status of I/R mice and H/R cells. MTT was performed to analyse the proliferation of H/R cells. H2S assay was used to evaluate the concentration of H2S in the myocardial tissues and peripheral blood of I/R mice. I/R-induced mediated myocardial injury and apoptosis were partially reversed by methionine-restricted diet (MRD) via the down-regulation of CSE expression and up-regulation of CHOP and active caspase3 expression. The decreased H2S concentration in myocardial tissues and peripheral blood of I/R mice was increased by MRD. Accordingly, in a cellular model of I/R injury established with H9C2 cells, cell proliferation was inhibited, cell apoptosis was increased, and the expressions of CSE, CHOP and active caspase3 were dysregulated, whereas NaHS treatment alleviated the effect of I/R injury in H9C2 cells in a dose-dependent manner. This study provided a deep insight into the mechanism underlying the role of MRD in I/R-induced myocardial injury.

Cyp2C19*2 Polymorphism Related to Clopidogrel Resistance in Patients With Coronary Heart Disease, Especially in the Asian Population: A Systematic Review and Meta-Analysis.

In recent years, the relationship between Cyp2C19*2 gene polymorphism and clopidogrel resistance reflected by platelet function assay has been studied extensively, but there is no clear conclusion yet. In order to evaluate the relationship between Cyp2C19*2 gene polymorphism and clopidogrel resistance more accurately, meta-analysis was conducted in this study. The I2 value taking 50% as the limit, the heterogeneity is judged as high or low, and then a random effect model or a fixed effect model is selected for statistical analysis. PubMed, EMBASE, Web of Science, CNKI, and China Wanfang database were searched, and the related literatures from the establishment of the database to May 2020 were collected and analyzed by STATA 15.0 software. A total of 3,073 patients were involved in 12 studies, including 1,174 patients with clopidogrel resistance and 1,899 patients with non-clopidogrel resistance. The results of this study showed that allele model (A vs. G): OR = 2.42 (95%CI: 1.97-2.98); dominant model (AA+GA vs. GG): OR = 2.74 (95%CI: 2.09-3.59); recessive model (AA vs. GA+GG): OR = 4.07 (95%CI: 3.06-5.41); homozygous model (AA vs. GG): OR = 5.70 (95%CI: 4.22-7.71); heterozygote model (GA vs. GG): OR = 2.32 (95%CI: 1.76-3.07), the differences were statistically significant. Also, the analysis of the Ethnicity subgroup indicated that the Asian allele model and the other four gene models were statistically significant. In conclusion, Cyp2C19*2 gene polymorphism is strongly associated with clopidogrel resistance. Allele A, genotype GA, AA, and GG + GA can increase clopidogrel resistance, especially in the Asian population.

Percolated Strain Networks and Universal Scaling Properties of Strain Glasses.

Strain glass is being established as a conceptually new state of matter in highly doped alloys, yet the understanding of its microscopic formation mechanism remains elusive. Here, we use a combined numerical and experimental approach to establish, for the first time, that the formation of strain glasses actually proceeds via the gradual percolation of strain clusters, namely, localized strain clusters that expand to reach the percolating state. Furthermore, our simulation studies of a wide variety of specific materials systems unambiguously reveal the existence of distinct scaling properties and universal behavior in the physical observables characterizing the glass transition, as obeyed by many existing experimental findings. The present work effectively enriches our understanding of the underlying physical principles governing glassy disordered materials.

Effects of phosphoinositide 3-kinase on protease-induced acute and chronic lung inflammation, remodeling, and emphysema in rats.

BACKGROUND: Phosphoinositide 3-kinase (PI3K) plays an important role in tissue inflammatory reactions and fibrotic processes. The objective of this study was to evaluate the potential mechanism and therapeutic effects of PI3K inhibitor on pancreatic elastase (PE)-induced acute and chronic lung inflammation, edema, and injury. METHODS: Rats were terminated at 7 or 28 days after an intratracheal challenge with PE and intranasal instillation with a PI3K inhibitor, SHBM1009. Alterations of airway epithelial cells and myofibroblasts were studied in vitro. MEASUREMENTS: Lung inflammation, edema, and injury; emphysema; and tissue remodeling were measured after PE instillation with or without treatment with PI3K inhibitor and budesonide. Cellular biologic functions were monitored. RESULTS: SHBM1009 could prevent PE-induced acute lung inflammation, edema, and injury, and chronic lung inflammation, remodeling, and emphysema. Different patterns of inhibitory effects of SHBM1009 and BEZ235, a dual PI3K/mechanistic target of rapamycin inhibitor, on PE-challenged epithelial cells were observed. PE per se reduced epithelial cell proliferation and stability through the inhibition of cell division rather than promoting cell death, in dose- and time-dependent patterns. Effects of PI3K inhibitors on cells were associated with the severity of PE challenges. CONCLUSIONS: PI3K plays a critical role in the development of acute and chronic lung injury, including the process of tissue remodeling and emphysema. PI3K inhibitors could be new therapeutic alternatives for chronic lung diseases.