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Background: Coronary microvascular dysfunction is crucial in determining myocardial ischemia; however, the relationship between epicardial coronary diameter stenosis (DS) and the index of microcirculatory resistance (IMR) remains unclear. We sought to explore the distribution of coronary angiography‐derived IMR (angio‐IMR) in patients with suspected myocardial ischemia. Methods: The study included 480 patients with suspected myocardial ischemia, all of whom underwent coronary angiography. According to the severity of coronary DS, patients were divided into three groups: mild (DS < 50%), intermediate (DS 50%–70%), and severe (DS > 70%). Angio‐IMR and fractional flow reserve (FFR) were calculated based on coronary angiography images through the principle of computational flow and pressure simulation. Results: Of the 480 patients, the mean age was 67.23 ± 9.44 years, with 55.4% male. There were 193 (40.2%) patients in the mild group, 189 (39.4%) patients in the intermediate group, and 98 (20.4%) patients in the severe group. The average angio‐IMR of the mild group was 30.8 ± 14.9, which was significantly higher than those of the intermediate group (26.7 ± 13.0) and the severe group (17.9 ± 8.4) (p <.001). In the correlation analysis, angio‐IMR was negatively correlated with DS (rho = −0.331, p =.001) and positively correlated with angio‐FFR (rho = 0.483, p <.001). By multivariate logistic regression analysis, angio‐FFR ≤ 0.8 (odds ratio, 0.184; 95% confidence interval, 0.106–0.321) was the only independent predictor of coronary microvascular dysfunction. Conclusion: In patients with suspected myocardial ischemia, coronary microcirculation is significantly associated with morphological and physiological coronary stenosis. (ClinicalTrials.gov: NCT05435898) [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common arrhythmia and can be treated with catheter ablation (CA) combined with left atrial appendage occlusion (LAAO). The study is designed to compare the safety and efficacy of guiding the combined procedure by digital subtraction angiography (DSA) with or without transesophageal echocardiography (TEE). Methods: From February 2019 to December 2020, 138 patients with nonvalvular AF who underwent CA combined with LAAO procedure were consecutively included, and two cohorts were built according to intraprocedural guidance (DSA or DSA with TEE). Periprocedural and follow‐up outcomes were compared with investigate the feasibility and safety between the two cohorts. Results: 71 patients and 67 patients were included in the DSA cohort and TEE cohort, respectively. Age and gender were comparable, despite the TEE cohort having a higher proportion of persistent AF (37 [55.2%] vs. 26 [36.6%]) and hemorrhage history (9 [13.4%] vs. 0). The procedure time of the DSA cohort was significantly reduced (95.7 ± 27.6 vs. 108.9 ± 30.3 min, p =.018), with a nonsignificant longer fluoroscopic time (15.2 ± 5.4 vs. 14.4 ± 7.1 min, p =.074). And the overall incidence of peri‐procedural complications was similar between cohorts. After an average of 24 months of clinical follow‐up, only three patients in the TEE cohort had ≤3 mm residual flow (p =.62). Kaplan–Meier estimates showed nonsignificant differences between the cohorts for freedom from atrial arrhythmia (log‐rank p =.964) and major adverse cardiovascular events (log‐rank p =.502). Conclusions: Compared with DSA and TEE guidance, DSA‐guided combined procedure could shorten the procedural time, while achieving similar periprocedural and long‐term feasibility and safety. [ABSTRACT FROM AUTHOR]

To solve a series of problems of Cu–Sn–Ti fillers, Ga is added to the fillers to promote its mechanical properties and microstructure. The metallographic structure of Cu–Sn–Ti–xGa filler metals is detected by optical microscope. Energy dispersive spectroscopy (EDS) areal, X‐ray diffraction (XRD), and differential thermal analysis (DSC) are used to analyze the morphology and microstructure of the fillers. The results show that doped Ga can significantly decrease the melting point and increase mechanical properties of the fillers. The shear strength of the filler metals with 1% Ga content is 160% higher than without Ga. In addition, it is also observed that a small amount of Ga refine the CuSnTi filler metals matrix structure. The diffusion of elements in the filler metals is detected. Compared with Sn solid solution, Ga tends to form a solid solution with Cu. When the Ga content is 2 wt%, the shear strength of the filler metal decreases due to the appearance of coarse crystals at the bottom of the dimple. Through the study of the reaction layer between diamond and filler metal, it is found that Ga can increase the thickness of the interface reaction layer. [ABSTRACT FROM AUTHOR]

Protein arginine methyltransferase 5 (PRMT5) has previously been reported to be upregulated in many malignant tumors. This study investigated the significance of PRMT5 in endometrial carcinoma (EC) and explored its function in tumorigenesis. Immunohistochemistry was performed to evaluate PRMT5 expression in 62 EC and 66 endometrial hyperplasia samples. The functions of PRMT5 were investigated by cell counting kit‐8, plate colony formation, wound healing, and transwell and flow cytometry assays. Quantitative reverse transcription‐polymerase chain reaction and western blotting were used to measure the expression of PRMT5, changes in estrogen receptor α (ERα), and related functional proteins. Coimmunoprecipitation was performed to examine the interaction of PRMT5 with ERα and its coactivator steroid receptor coactivator‐1 (SRC1). Compared to endometrial hyperplasia tissue, PRMT5 was overexpressed in endometrioid adenocarcinoma (EAC) but not overexpressed in mucinous EC. The main expression pattern of PRMT5 in EAC was cytoplasmic. However, the positive cases of endometrial hyperplasia showed both cytoplasmic and nuclear positivity in the endometrial glands or were mainly positive in stromal cells. Knockdown of PRMT5 significantly inhibited the growth and migration ability of EAC cells and promoted their apoptosis by regulating cyclin D1, c‐myc, p53, and Bcl2 proteins. Furthermore, PRMT5 could form a complex with ERα and SRC1 to promote the expression of ERα. In conclusion, PRMT5 plays a significant role in the progression of EAC by interacting with ERα and impacting the cell cycle signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Acute left atrial ridge (LAR) lesions have been observed following atrial fibrillation (AF) ablation. However, LAR lesions had not yet been quantitatively evaluated and their influence on procedure combining cryoballoon (CB) ablation with left atrial appendage closure (LAAC) remained to be explored. Methods: The profile of LAR lesions was measured by transesophageal echocardiography (TEE) in 117 consecutive nonvalvular AF patients, who underwent the combined procedure of CB ablation and LAAC. We thoroughly investigated how LAR lesions correlated with baseline variables and clinical outcomes. Results: A total of 95 out of 96 available TEE images presented prominent acute LAR lesions. In terms of dimensions, there was a greater change in width (Δwidth = 3.6 ± 2.3 mm) than the thickness (Δthickness = 2.6 ± 3.5 mm), and the outer ostium was narrowed (Δouter ostium diameter = −3.4 ± 4.0 mm), while the inner ostium remained unchanged. A higher nadir temperature when freezing the left superior pulmonary vein (LSPV) led to an LAR lesion with a two times greater width (adjusted odds ratio = 1.16; 95% confidence interval, 1.02–1.31). In the evaluation of LAAC outcomes, four patients implanted with Watchman devices had minimal residual flow at the inferior border, while two implanted with LAmbre devices developed residual flow at the LAR side. Clinical outcomes were similar between groups divided by lesion size. Conclusion: Acute LAR lesions frequently occurred following the CB ablation combined procedure, and lesion width positively correlates with LSPV nadir temperature. The presence of these lesions affects the measurement of pacifier devices but has little impact on that of occluder devices. [ABSTRACT FROM AUTHOR]

Photothermal‐material‐assisted solar‐steam generation has recently attracted intensive attention due to its superior evaporation rate with high energy conversion efficiency for desalination. In this work, a simple approach for fabrication of porous carbon nanofoam (PCN) is reported, which is prepared by the carbonization of pitch using a combination of CaCO3 and NaCl templates, Meanwhile, NaCl saturated solution acts as a porogen to produce micropores and mesopores as solar receiver for efficient solar steam generation. The as‐prepared PCN shows excellent porosity and mesoporous feature with an average pore size of 26.8 nm. It also shows superior light absorption of 88% and better thermal insulation (thermal conductivity 0.993 W m−1 K−1). Based on these characteristics, the as‐prepared PCN can be used as a promising solar receiver. Under 1 sun, 2 sun, and 3 sun irradiation, the PCN‐based solar receiver shows high energy conversion efficiencies of 88%, 86%, and 84%, respectively. Taking advantage of the abundant, low‐cost, and commercial availability of pitch as well as its simple and cost‐effective manufacture method, the PCN‐based solar receiver may hold great potential for a broad variety of solar‐steam generation applications, for instance, fresh water production, power generation, desalination, and so on. [ABSTRACT FROM AUTHOR]

Background and Aim: DNA hypermethylation has emerged as a novel molecular biomarker for the diagnosis and prognosis prediction of many cancers. We aimed to identify clinically useful biomarkers regulated by DNA methylation in hepatocellular carcinoma (HCC). Methods: Genome‐wide methylation analysis in HCCs and paired noncancerous tissues was performed using an Illumina Infinium HumanMethylation 450K BeadChip array. Methylation‐specific polymerase chain reaction and pyrosequencing were used to validate the methylation status of selected genes in 100 paired HCCs and noncancerous samples. Results: A total of 97 027 (20.0%) out of 485 577 CpG sites significantly were differed between HCC and noncancerous tissues. Among all the significant CpG sites, 48.8% are hypermethylated and 51.2% are hypomethylated in HCCs. Multiple signaling pathways (AMP‐activated protein kinase, estrogen, and adipocytokine) involved in gene methylation were identified in HCC. FES was selected for further analysis based on its high level of methylation confirmed by polymerase chain reaction and pyrosequencing. The result showed that FES hypermethylation was correlated with tumor size (0.001), serum alpha fetoprotein (0.023), and tumor differentiation (0.006). FES protein was significantly downregulated in 51/100 (51%) HCCs, and 94.12% (48/51) of them were due to promoter hypermethylation. Both FES hypermethylation and protein downregulation were associated with the progression‐free survival and overall survival of HCC patients. Overexpressed and knockdown of FES confirmed its inhibitory effect on the proliferation and migration of HCC cells. Conclusions: We identified many new differentially methylated CpGs in HCCs and demonstrate that FES functions as a tumor suppressor gene in HCC and its methylation status could be used as an indicator for prognosis of HCC. [ABSTRACT FROM AUTHOR]

Protein tyrosine nitration is implicated in the occurrence and progression of pathological conditions involving free radical reactions. It is well recognized that hemin can catalyze protein tyrosine nitration in the presence of nitrite and hydrogen peroxide. Generally, the catalytic efficiency is positively correlated to its peroxidase activity. In this study, however, it is found that the efficiency of hemin in catalyzing protein tyrosine nitration is largely suppressed after functionalization with graphene derivatives, even though its peroxidase-like activity is more than quadrupled. Further studies show that the oxidation of tyrosine is still observed for these composites; dityrosine formation, however, is greatly inhibited. Furthermore, these composites also exhibit strong effects on the oxidation of nitrite into nitrate. Therefore, we propose a mechanism in which hemin-graphene derivatives facilitate the oxidation of tyrosine and nitrite to produce tyrosyl radicals and nitrogen dioxide radicals in the presence of hydrogen peroxide, but graphene interlayers serve as barriers that hinder radical-radical coupling reactions; consequently, protein tyrosine nitration is restrained. This property of hemin-graphene derivatives, by which they catalyze substrate oxidation but suppress radical-radical coupling reactions, shows their great potential in selective oxidation procedures for byproduct removal. [ABSTRACT FROM AUTHOR]

Peroxynitrite and heme peroxidases (or heme)-H2O2-NaNO2 system are the two common ways to cause protein tyrosine nitration in vitro, but the effects of antioxidants on reducing these two pathways-induced protein nitration and oxidation are controversial. Both nitrating systems can dose-dependently induce triosephosphate isomerase (TIM) nitration, however, heme-H2O2-NaNO2 was less destructive to protein secondary structures and led to more nitrated tyrosine residue than 3-morpholinosydnonimine hydrochloride (SIN-1, a peroxynitrite donor). Both of desferrioxamine and catechin could inhibit TIM nitration induced by heme-H2O2-NaNO2 and SIN-1 and protein oxidation induced by SIN-1, but promoted heme-H2O2-NaNO2-induced protein oxidation. Moreover, the antagonism of natural phenolic compounds on SIN-1-induced tyrosine nitration was consistent with their radical scavenging ability, but no similar consensus was found in heme-H2O2-NaNO2-induced nitration. Our results indicated that peroxynitrite and heme-H2O2-NaNO2-induced protein nitration was different, and the later one could be a better model for anti-nitration compounds screening. [ABSTRACT FROM AUTHOR]

An easy and versatile Cu-catalyzed propargylic substitution process is presented. Using easily prepared prochiral dichloro substrates, readily available Grignard reagents together with catalytic amount of copper salt and chiral ligand, we accessed a range of synthetically interesting trisubstituted chloroallenes. Substrate scope and nucleophile scope are broad, providing generally high enantioselectivity for the desired 1,3-substitution products. The enantioenriched chloroallenes could be further transformed into the corresponding trisubstituted allenes or terminal alkynes bearing all-carbon quaternary stereogenic centers, through the copper-catalyzed enantiospecific 1,1/1,3-substitutions. The two successive copper-catalyzed reactions could be eventually combined into a one-pot procedure and different desired allenes or alkynes were obtained respectively with high enantiomeric excesses. [ABSTRACT FROM AUTHOR]

Highly conductive PPy/graphite nanosheets/rare earth ions (PPy/nanoG/RE3+) composites were prepared via in-situ polymerization with p-toluenesulfonic acid as a dopant and FeCl3 as an oxidant. The microstructures of nanoG and PPy/nanoG/RE3+ were characterized by the SEM and TEM examinations. It was found that nanoG and PPy nanospheres formed the uniform composite with the PPy nanospheres embedded on the nanoG surface and/or filled between the nanoG. The effects of nanoG and RE3+ on the electrical conductivity and electrochemical performance of the composites were investigated. The results showed that the nanoG and RE3+ as the filler had effect on the conductivity and electrochemical performance of PPy/nanoG/RE3+ composites, which played an important role in forming a conducting network in PPy matrix. A specific capacitance of as high as 175 F/g at a current density of 1 A/g was achieved over the PPy/nanoG/Gd3+ composite. The capacitance of the PPy/nanoG/Gd3+ composite decreased only 5.1% after 800 charging/discharging cycles at a current density of 1 A/g. POLYM. ENG. SCI., 54:2731-2738, 2014. © 2013 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

A very recent epidemiological study provided strong support for nobiletin (NOB) as a potential candidate chemopreventive agent against cancer. From the pharmacology point of view, drug-protein interactions are determining factors in therapeutic, pharmacodynamic and toxicological drug properties. In this work, for the first time, detection of NOB at near-physiological conditions was accomplished by means of capillary electrophoresis-frontal analysis (CE-FA), and then the binding constants of NOB with bovine serum albumin (BSA) at the same conditions were determined. Complexation of NOB-BSA led to a decrease of the height for free NOB with increasing concentration of BSA. These results revealed the presence of a single class of binding site on BSA, and provided the binding constant of 103/ m, showing the strong affinity of NOB for BSA. Furthermore, circular dichroism spectra showed that, when the molar ratio of NOB to BSA was up to 2:1, NOB did not affect the overall protein conformation significantly and the protein thus retained a native-like structure. These results may provide important information for preclinical studies of nobiletin in pharmaceutical research. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An easy and versatile Cu-catalyzed propargylic substitution process is presented. [ABSTRACT FROM AUTHOR]

This method yields axially chiral chloroallenes with good enantioselectivity, which can be further transformed to trisubstituted allenes or terminal alkynes with propargylic quarternary stereocenters. [ABSTRACT FROM AUTHOR]

An asymmetric allylic alkylation reaction is used for the synthesis of fluorinated alkenes bearing a quaternary stereocenter. [ABSTRACT FROM AUTHOR]

Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P <0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P =0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P =0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.

Background: Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown., Methods and Results: In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates. Moreover, we generated cardiomyocyte-specific TIM50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by TIM50. Meanwhile, expression of the ASK1-JNK/P38 axis was increased in TIM50-deficient mice, and TIM50 overexpression decreased the activity of the ASK1-JNK/P38 axis. Finally, we treated mice with the antioxidant N-acetyl cysteine to reduce oxidative stress. After N-acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency were all remarkably reversed., Conclusions: These data indicated that TIM50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress. TIM50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)