Liquiritigenin alleviates doxorubicin-induced chronic heart failure via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway.

Chronic heart failure (CHF) is one of the most common chronic diseases with increasing incidence and mortality. Liquiritigenin (LQG) is shown to protect mice from cardiotoxicity. However, its underlying mechanism remains unclear. Our study aimed to reveal the role of ARHGAP18 in LQG-mediated cardioprotective effects in CHF. In the current study, CHF cell model and rat model were established by the application of doxorubicin (DOX). The reactive oxygen species (ROS) level and cell apoptosis were determined by flow cytometry. The cardiac function of rats was evaluated by measuring left ventricular systolic pressure, left ventricular end diastolic pressure, and serum level of lactate dehydrogenase and brain natriuretic peptide. The expression of active RhoA was elevated and that of ARHGAP18 was decreased in DOX-induced CHF cell model. ARHGAP18 could reduce DOX-induced RhoA activation, ROS elevation, and cell apoptosis. Meanwhile, the knockdown of ARHGAP18 could promote the activation of RhoA, the level of ROS, and the rate of cell apoptosis, which could be reversed by the application of RhoA inhibitor. LQG promoted the expression of ARHGAP18 and exerted similar effects of ARHGAP18 in CHF cell model. The application of LQG could also reverse the effects mediated by ARHGAP18 knockdown. Moreover, LQG significantly improved cardiac function and ameliorated DOX-induced cardiotoxicity of CHF rats. In conclusion, LQG could alleviate DOX-induced CHF via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway. LQG was a potential agent for CHF treatment.

TiO2 modified orthocortical and paracortical cells having enhanced photocatalytic degradation and photoreduction properties.

In this study, cortical cells resultant from wool fibers were loaded with TiO2 nanoparticles in a hydrothermal process and were then engineered as organic-nonorganic hybrid composite photocatalysts for both photodegradation of organic dyes and photoreduction of heavy metal ions. The microstructure and photocatalytic properties of TiO2 modified cortical cells (i.e. both orthocortical and paracortical cells) were systematically characterized using a series of analytical techniques including FESEM, TEM, element analysis, Mott-Schottky curve, BET specific surface area, Zeta potentials, as well as XRD, FTIR, XPS, DRS, PL, UPS, EDS and ESR spectra. Their photocatalytic performance and trapping experiments of the TiO2 modified cortical cells were measured in the photodegradation of methylene blue (MB) dye and Congo Red (CR) dye as well as the photoreduction of Cr(VI) ions under visible light irradiation. It was found that anatase TiO2 nanoparticles were chemically grafted on the surface of the two cortical cells via O-Ti4+/O-Ti3+ bonds, and that TiO2 nanoparticles were formed inside the orthocortical cells in the hydrothermal process. The TiO2 modified orthocortical and paracortical cells possessed much higher photocatalytic efficiency than the commercially available TiO2 nanoparticle powder, Degussa P25, in the photodegradation of cationic MB dye and photoreduction of Cr(VI) ions, while their photocatalytic efficiency in the photodegradation of anionic CR dye is smaller because of their greater negative Zeta potentials and photogenerated holes as the main reactive radical species. In comparison with the TiO2 modified paracortical cells, the higher photocatalytic efficiency of the TiO2 modified orthocortical cells was demonstrated in the photodegradation of MB dye solution and this might be due to both the S-doped TiO2 nanoparticles infiltrated into the naturally hydrophilic orthocortical cells and the primary reactive radical species of photogenerated holes being trapped in the cells.

Photocatalytic mechanism and performance of a novel wool flake-BiFeO3nanosheet-TiO2core-shell-structured composite photocatalyst.

In this study, BiFeO3(BFO) nanosheets ground from BFO particles were first incorporated with wool flakes to construct sandwich-like wool-BFO composites using the vibration-assisted ball milling technique in freezing conditions. The wool-BFO composites were then loaded with a thick layer of TiO2nanoparticles to prepare the core-shell-structured wool-BFO-TiO2composites using a hydrothermal synthesis process. The microstructure of the core-shell wool-BFO-TiO2composites and its photocatalytic applications were systematically examined using a series of characterization methods. Trapping experiments and electron spin resonance spectra were also employed to judge the active radical species like superoxide radicals (·O2-), singlet oxygen (1O2), holes (h+), and hydroxyl radicals (·OH) using benzoquinone, furfuryl alcohol, ethylenediamine tetraacetic acid, and tert-butanol as the scavengers, respectively. The photodegradation performance of the wool-BFO-TiO2composites was measured using more resistant methyl orange (MO) dye as the pollutant model. In comparison with the wool-TiO2or wool-BFO composites, the superior photocatalytic properties of the wool-BFO-TiO2composites under visible light irradiation were attributed to the presence of mesopores and macropores, the large specific surface area and intimate interface between wool-BFO composites and TiO2nanoparticles, the coexistence of Fe3+, Fe2+, Bi3+, Bi(3-x)+, Ti4+, and Ti3+species, and the strong visible light harvesting, thus leading to the fast separation of photogenerated electron-hole pairs. The wool-BFO-TiO2composites could be used for the repeated photodegradation of organic pollutants and be recycled easily using a magnet. The active radical species of the wool-BFO-TiO2composites were ·O2-and1O2rather than ·OH and h+, which were involved in the photodegradation of MO dye under visible light irradiation.

Distant hybrids of Heliocidaris crassispina (♀) and Strongylocentrotus intermedius (♂): identification and mtDNA heteroplasmy analysis.

BACKGROUND: Distant hybridization between the sea urchin Heliocidaris crassispina (♀) and the sea urchin Strongylocentrotus intermedius (♂) was successfully performed under laboratory conditions. A new variety of hybrid sea urchin (HS hybrid) was obtained. However, the early-development success rates for the HS hybrids were significantly lower than those of purebred H. crassispina or S. intermedius offspring. In addition, it was difficult to distinguish the HS-hybrid adults from the pure H. crassispina adults, which might lead to confusion in subsequent breeding attempts. In this study, we attempted to develop a method to quickly and effectively identify HS hybrids, and to preliminarily investigate the molecular mechanisms underlying the poor early-development success rates in the HS hybrids. RESULTS: The hybrid sea urchins (HS hybrids) were identified both morphologically and molecularly. There were no significant differences in the test height to test diameter ratios between the HS hybrids and the parents. The number and arrangement of ambulacral pore pairs in the HS hybrids differed from those of the parental lines, which might serve as a useful morphological character for the identification of the HS hybrids. A primer pair that identified the HS hybrids was screened by comparing the mitochondrial genomes of the parental lines. Moreover, paternal leakage induced mitochondrial DNA heteroplasmy in the HS hybrids, which might explain the low rates of early development success in these hybrids. CONCLUSIONS: The distant-hybrid sea urchins were accurately identified using comparative morphological and molecular genetic methods. The first evidence of mtDNA heteroplasmy after the distant hybridization of an echinoderm was also provided.

Smartphone-based application to improve medication adherence in patients after surgical coronary revascularization.

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse events after coronary artery bypass grafting (CABG). However, adherence to secondary preventive drugs after CABG is often poor. With the increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve medication adherence. We aimed to evaluate the effectiveness and feasibility of using a smartphone-based application to improve medication adherence in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical coronary revascularizatION: medication adherence (MISSION-2) study is a multicenter randomized controlled trial that planned to enroll over 1000 patients who underwent isolated CABG at one of four large teaching hospitals in China; all enrolled participants had access to a smartphone and were able to operate at least three smartphone applications. The investigators randomly assigned the participants to one of two groups: (1) the intervention group with an advanced smartphone application for 6 months which was designed specifically for this trial and did not exist before. Participants could receive medication reminders and cardiac health education by the smartphone application or (2) the control group with usual care. The primary outcome was CABG secondary preventive medication adherence as measured by the translated Chinese version of the 8-item Morisky Medication Adherence Scale (MMAS-8) at 6 months after randomization. The secondary outcomes were mortality, major adverse cardiovascular and cerebrovascular events (MACCE), cardiovascular rehospitalization, self-reported secondary preventive medication use after 6 months of follow-up, blood pressure (BP), body mass index (BMI), and self-reported smoking status. All analyses were conducted using the intention-to-treat principle. RESULTS: A total of 1000 patients (mean age, 57.28 [SD, 9.09] years; 85.5% male) with coronary heart disease after CABG were enrolled between September 2015 and September 2016 and were randomly assigned to the intervention (n = 501) or control group (n = 499). At 6 months, the proportion of low-adherence participants, categorized by MMAS-8 scores, was 11.8% in the intervention group and 11.7% in the control group (RR = 1.005, 95% CI 0.682 to 1.480, P = 1.000). Similar results were found in sensitivity analyses that considered participants who withdrew from the study, or were lost to follow-up as nonadherent. There were no significant differences in the secondary clinical outcome measures, and there were no significant differences in the primary outcome across the subgroups tested. In the intervention group, the proportion of participants who used and operated the application during the first month after CABG was 88.1%; however, the use rate decreased sharply from 42.5% in the second month to 9.2% by the end of the study (6 months). CONCLUSIONS: A smartphone-based application supporting secondary prevention among patients after CABG did not lead to a greater adherence to secondary preventive medications. The limited room for improvement in medication adherence and the low participants' engagement with the smartphone applications might account for these non-significant outcomes.

Elevated postoperative serum uric acid is associated with major adverse events following coronary artery bypass grafting.

BACKGROUND: Few data are available on the association between postoperative serum uric acid (SUA) level and poor survival in patients undergoing coronary artery bypass grafting (CABG). We evaluated the relationship between postoperative SUA and major adverse cardiac and cerebrovascular events (MACCE) among patients undergoing CABG. METHODS: This study used data from 1614 consecutive patients undergoing CAGB at Fuwai Hospital (Beijing, China) from 2011 to 2015. Patients were stratified into statistical quartiles of postoperative SUA (between 6 and 18 hours after cardiac surgery): less than 203.7, 203.7 to 254.1, 254.1 to 316.6, and ≥316.6 µmol/L. The association of postoperative SUA with MACCE (ie, death, myocardial infarction [MI], stroke, or repeat revascularization) and the composite endpoint of mortality/MI were assessed. RESULTS: Patients had a mean age of 60.3 ± 8.4 years, and 79.3% were male. During mean follow-up of 2.5 ± 0.7 years, MACCE occurred in 201 (12.5%) patients. In separate multivariable regression models, postoperative SUA level was positively associated with in-hospital MACCE (highest vs lowest SUA quartile: odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.29, 4.48; P = .006) and in-hospital composite endpoint of mortality/MI (OR: 2.88; 95% CI: 1.45, 5.72; P = .003), respectively. And elevated postoperative SUA level was independently associated with MACCE (Hazard ratio [HR]: 1.70; 95% CI: 1.12, 2.57; P = .01) and the composite endpoint of mortality/MI (HR: 2.42; 95% CI: 1.32, 4.43; P = .004) respectively within 3 years after CABG. CONCLUSIONS: Elevated postoperative SUA level is associated with poor clinical outcomes after CABG. Patients with high postoperative SUA levels after CABG might require to be closely monitored.

A novel MKK gene (AjMKK3/6) in the sea cucumber Apostichopus japonicus: Identification, characterization and its response to pathogenic challenge.

The mitogen-activated protein kinase kinases (MKKs) are key components of MAP kinase (MAPK) cascades and function as redox-regulated signaling factors in pathological and physiological processes. In this study, we identified a novel MKK3/6 gene in the sea cucumber Apostichopus japonicus (designated as AjMKK3/6) by transcriptome database mining and rapid amplification of cDNA ends (RACE) approaches. Sequence analysis and protein structure prediction showed that AjMKK3/6 is highly conserved as compared to those from other invertebrate and vertebrate species. Molecular phylogeny result revealed that AjMKK3/6 exhibited a closest relationship with that from Strongylocentrotus purpuratus. Quantitative real-time PCR was employed to determine the expression profiles of AjMKK3/6 in healthy adult A. japonicus tissues and in coelomocytes after Vibrio splendidus infection in vivo, respectively. As results shown, AjMKK3/6 was ubiquitously expressed in all examined tissues of healthy adult A. japonicus with a relative expression level from high to low as body wall > tube feet > coelomocytes > respiratory tree > intestine > longitudinal muscle. Significant expression changes of AjMKK3/6 in coelomocytes were observed at 12 h- and 72 h-after V. splendidus infection, respectively. In general, the current study will enrich our knowledge of characterizations and immno-functions of MKK3/6 in sea cucumbers.

Characterization and expression analysis of a thioredoxin-like protein gene in the sea cucumber Apostichopus japonicus.

As the most important disulfide bond reducates of intracellular oxidordeuctase, thioredoxin (TRX) plays a crucial role in maintaining reducing state of intracellular proteins to normally perform their function. In this study, a cDNA of TRX-like protein gene from Apostichopus japonicus (denoted as AjTRX) was cloned and characterized. The full-length cDNA of AjTRXwas of 1870 bp, consisting of a 5'-UTR of 101 bp, a long 3'-UTR of 887 bp and a 882 bp open reading frame (ORF) encoding a 293 amino acids. The predicted molecular mass and the theoretical PI of the deduced amino acids of AjTRX were 32.3 kDa and 5.52, respectively. Phylogenetic trees showed that AjTRX had a closer evolution relationship with TRX from Strongylocentrotus purpuratus. AjTRX was found to be ubiquitously expressed in all examined tissues including longitudinal muscle, coelomocytes, tube feet, intestine, respiratory tree and body wall indicating a general role in physiological processes. Temporal expression pattern of AjTRX in coelomocytes showed that AjTRX reached two peak expression levels at 8 h and 48 h after Vibrio splendidus challenge with a 8.6 and 9.3-fold increase compared to their control groups, respectively. The recombinant AjTRX protein (rAjTRX) displayed obvious antioxidant activity in a dose-dependent manner, and the higher reducing activity was detected in 20 µM experimental group. All these results strongly suggested that AjTRX could play an important role as an antioxidant in a physiological context, and might be involved in the process of bacterial challenge.

Identification and characterization a novel transcription factor activator protein-1 in the sea cucumber Apostichopus japonicus.

The transcription factor activator protein-1 (AP-1) is an important gene expression regulator with typical Jun and region-leucine zipper (bZIP) domains and can respond to a plethora of physiological and pathological stimulus. In this study, we identified a novel AP-1 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjAP-1). The full-length of AjAP-1 was of 2944 bp including a 5' untranslated region (UTR) of 201 bp, a 3' UTR of 1753 bp and a putative open reading frame of 990 bp encoding a polypeptide of 329 amino acid residues. Two representative domains of Jun and bZIP as well as two nuclear localization signals (NLSs) were also detected in deduced amino acid of AjAP-1. Spatial distribution expression indicated that AjAP-1 was ubiquitously expressed in all examined tissues with predominant expression in the body wall, moderate in the tube feet, respiratory tree and colemocytes and slightly weak in the intestine and longitudinal muscle. Time-course expression analysis in intestine and coelomocytes revealed that AjAP-1 both reached its peak expression at 4 h after Vibrio splendidus challenge with a 2.6 and 8.2-fold increase compared to their control groups, respectively. Taken together, all these results suggested that AjAP-1 was a novel immune factor and might be involved in the processes of anti-bacteria response in sea cucumber.

Strongly active and environmentally friendly WO3/C3N4 photocatalysts for converting cyclohexane to cyclohexanone under ambient conditions.

C-H bond activation under mild conditions remains a great challenge in the chemical industry, while catalytic cyclohexane oxidation is inefficient and often requires organic solvents and strong oxidants. This study constructed a C3N4/WO3 Z-type heterojunction catalyst to efficiently convert cyclohexane into cyclohexanone and cyclohexanol (KA oil) through aqueous phase oxidation by O2 under visible light irradiation. With strong redox performance and high photogenerated carrier separation ability, the proposed composite catalyst can produce the key active species for cyclohexane oxidation in the H2O-O2 system. The reaction mechanism was clarified through experiment and DFT theory calculation. Cyclohexane was converted into cyclohexyl radical under the action of ·OH, and ·O2- converted most products into cyclohexanone. The catalyst can be recycled under optimized process conditions while reaching a KA oil yield of 139.73 µmol g-1 h-1 and a selectivity of 93.1%.

Identifying coronary artery bypass grafting patients at high risk for adverse long-term prognosis using serial health-related quality of life assessments.

BACKGROUND: Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients. METHODS: The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes. RESULTS: The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07-2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09-2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively). CONCLUSIONS: Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Clinical Outcomes of Minimally Invasive Fixation with Pre-Bent Elastic Stable Intramedullary Nails for the Treatment of Distal Radius Metaphyseal Diaphysis Junction Fractures in Children.

OBJECTIVE: Although mini-plate fixation is an attractive treatment option for distal radius metaphyseal diaphysis junction (DRMDJ) fractures in children, the benefits of minimally invasive fixation (MIF) with pre-bent elastic stable intramedullary nails (MIF) remain underexplored. Therefore, this study aimed to evaluate the clinical efficacy of MIF administration in children with DRMDJ fractures. METHODS: This retrospective study enrolled 40 patients with DRMDJ fractures who underwent MIF or mini-plate fixation from January 2016 to January 2021. Radiographic parameters, such as palmar inclination and ulnar deflection angle, were examined postoperatively to assess the anatomical reduction of the wrist joint. Clinical outcomes, including the range of wrist flexion and back extension, were examined to analyze the recovery of the wrist range of motion. Additionally, the Gartland-Werley scoring system was used to assess the recovery status of wrist function and healing condition. The student t-test and χ2 test were used to compare differences among groups. RESULTS: All included patients successfully underwent the operation and were followed up for 12-24 months. Patients in the MIF group had a smaller surgical incision length (0.49 ± 0.06 cm) compared to those in the mini-plate fixation group (4.41 ± 0.73 cm) (t = 22.438, p = 0.000). Palmar inclination and ulnar deflection were within the normal range in patients of both groups, and the fractures were successfully anatomically reduced. Moreover, wrist flexion and back extension in the MIF group and mini-plate group were (72.50° ± 0.64° vs. 70.18° ± 0.56°) and (59.55° ± 1.75° vs. 60.04° ± 1.37°), and differences were statistically significant (t = 2.708, p = 0.010 and t = 0.885, p = 0.382, respectively). Furthermore, MIF treatment resulted in a higher proportion of excellent Gartland-Werley scores (94.44%) than mini-plate fixation (86.36%) (p = 0.390). In addition, one case in the mini-plate fixation group experienced re-fracture following the removal of the internal fixation, and the fracture healed after reduction and cast fixation. All patients achieved satisfactory bone healing without other complications. CONCLUSION: Compared with mini-plate fixation, MIF has the advantages of small incision length, superior range of motion of thr wrist joint, and better maintenance of the physiological radian, providing a promising approach for clinical and surgical treatment of DRMDJ fractures.

Post-synthetic Chemical Fixation of Fe2+ in MOF to Prepare Fe2 N-Embedded N-Doped Graphene Nanoribbons for Superior Oxygen Reduction Reaction.

The construction of efficient non-precious metal electrocatalysts for oxygen reduction reaction (ORR) with controlled structures and active sites is of fundamental importance for the wide utilization of hydrogen fuel cells. Herein, we report a controllable chemical fixation strategy that enables the simultaneous optimization in both of local and external structure of the Fe-N-C catalyst. The post-synthetic single-atomic chemical fixation of Fe2+ ions in coordinated-free bi-pyridine sites combined with the carbonation afford a Fe2 N-embedded N-doped graphene nanoribbon (Fe2 N/NGNR) with dispersing Fe2 N nanoparticles embedded in NGNR. When used as ORR electrocatalyst, Fe2 N/NGNR exhibits a half-wave potential of 0.87 V and 0.79 V vs. RHE in alkaline and acid medium, respectively, comparable to commercial Pt/C (20 wt%) catalysts. The prominent ORR activity of Fe2 N/NGNR is verified an H2 -O2 fuel cell which displayed a peak power density of 307.7 mW/cm2 when using the Fe2 N/NGNR as the catalyst in the cathode electrode.

Impact of coronary total occlusion on graft failure and outcomes of coronary artery bypass grafting.

OBJECTIVE: The study objective was to assess the impact of chronic total occlusion on long-term graft failure and outcomes in patients who underwent coronary artery bypass grafting. METHODS: We conducted an observational study involving a single-center subgroup of the CORONARY trial. At 6 to 9 years after coronary artery bypass grafting, all alive patients were invited for coronary computed tomography angiography and clinical follow-up. We assessed the association between chronic total occlusion graft and failing graft showing Fitzgibbon type B or O. Risk factors associated with chronic total occlusion graft failure were assessed. The impact of chronic total occlusion on clinical outcomes was analyzed, including death, myocardial infarction, and repeated revascularization. RESULTS: A total of 349 patients undergoing coronary artery bypass grafting were enrolled between May 2007 and October 2011. Of 301 alive patients at follow-up time (median, 6.8 years; interquartile range, 6.0-8.0 years), repeat coronary computed tomography angiography was performed in 206 patients (68.4%) with 723 grafts (154 chronic total occlusion grafts and 569 nonchronic total occlusion grafts). Chronic total occlusion graft was significantly associated with an increased risk of long-term graft failure after adjustment for patient- and graft-level characteristics (adjusted odds ratio, 2.27; 95% confidence interval, 1.42-3.62; P < .001). Arterial graft, side-to-side anastomosis, higher graft flow, and antiplatelet therapy at discharge were associated with chronic total occlusion graft patency. The presence of 1 or more chronic total occlusions was not significantly associated with long-term composite of death, myocardial infarction, or repeat revascularization (adjusted hazard ratio, 0.91; 95% confidence interval, 0.54-1.51; P = .707). CONCLUSIONS: Chronic total occlusion graft was associated with an increased risk of graft failure. Surgical technique and guideline-directed medical therapy should be noted to improve chronic total occlusion graft patency.

Long-Term Graft Patency After Off-Pump and On-Pump Coronary Artery Bypass: A CORONARY Trial Cohort.

BACKGROUND: Randomized controlled trials have compared the early and midterm prognosis of on-pump coronary artery bypass grafting (CABG) and off-pump CABG. However the results are controversial, and there is limited information on graft patency and long-term outcomes. METHODS: Between May 2007 and October 2011, 349 patients were randomized to off-pump or on-pump CABG as part of the CORONARY trial at Fuwai Hospital. The primary outcome was coronary bypass graft patency, which was assessed at a mean of 6.7 ± 1.7 years after surgery by multidetector computed tomography. A secondary endpoint was a composite outcome of death, nonfatal myocardial infarction, repeat coronary revascularization, or stroke; mean follow-up was 6.5 ± 1.7 years. Graft patency was compared between the off-pump and on-pump CABG treatment arms in 206 patients with follow-up computed tomography. RESULTS: During the follow-up period 107 patients were in the off-pump CABG group and 99 in the on-pump group. These patients underwent a total of 723 grafts, and the overall rate of graft patency did not differ significantly between the off-pump and on-pump groups (87.4% vs 88.9%, P = .527). The patency rate of the posterior descending branch was lower than average. Higher incidences of mortality, nonfatal myocardial infarction, and repeat revascularization were found in the off-pump patients; however it did not reach significance. CONCLUSIONS: There were no statistical differences in graft patency rates in off-pump versus on-pump CABG patients during long-term follow-up. The on-pump CABG group appeared to have a better long-term prognosis even with no statistical differences for the limited study population.

Nonsense-mediated decay factor SMG7 sensitizes cells to TNFα-induced apoptosis via CYLD tumor suppressor and the noncoding oncogene Pvt1.

Nonsense-mediated decay (NMD) proteins are responsible for the surveillance and degradation of aberrant RNAs. Suppressor with morphogenetic effect on genitalia 7 (SMG7) is an NMD complex protein and a regulator of tumor necrosis factor (TNF)-induced extrinsic apoptosis; however, this unique function has not been explored in detail. In this study, we show that loss of Smg7 leads to unrestricted expression of long noncoding RNAs (lncRNAs) in addition to NMD targets. Functional analysis of Smg7-/- cells showed downregulation of the tumor suppressor cylindromatosis (CYLD) and diminished caspase activity, thereby switching cells to nuclear factor-κB (NF-κB)-mediated protection. This positive relationship between SMG7 and CYLD was found to be widely conserved in human cancer cell lines and renal carcinoma samples from The Cancer Genome Atlas. In addition to CYLD suppression, upregulation of lncRNAs Pvt1 and Adapt33 rendered cells resistant to TNF, while pharmacologic inhibition of NF-κB in Pvt1-overexpressing TNF-resistant cells and Smg7-deficient spheroids re-established TNF-induced lethality. Thus, loss of SMG7 decouples regulation of two separate oncogenic factors with cumulative downstream effects on the NF-κB pathway. The data highlight a novel and specific regulation of oncogenic factors by SMG7 and pinpoint a composite tumor suppressor role in response to TNF.

Tunable and convenient synthesis of highly dispersed Fe-N x catalysts from graphene-supported Zn-Fe-ZIF for efficient oxygen reduction in acidic media.

The development of low-cost, efficient and stable electrocatalysts for the oxygen reduction reaction (ORR) is desirable but remains a great challenge. We report a convenient and efficient synthesis approach of highly dispersed Fe-N x catalysts for ORR. Typically, Fe-Zn-ZIF (zeolitic imidazolate frameworks) nanocrystals cast as precursor and graphene as supports, highly dispersed Fe-N x species were fabricated with PVP (polyvinyl pyrrolidone) as surfactant via pyrolysis. With the help of graphene and surfactant, the agglomeration of iron particles has been avoided during pyrolysis, and the size and morphology of ZIF particles intercalating into the graphene layers can be regulated precisely as well. The amount of Fe-N x active sites in C-rGO-ZIF catalyst arrived 4.29%, which is obviously higher than most monodispersed non-precious metal catalysts reported. The obtained C-rGO-ZIF catalyst exhibits a high onset potential of 0.89 V and a half-wave potential of 0.77 V, which is only 30 mV away from Pt/C in acidic media. The active sites of the catalyst was characterized and found to be the highly dispersed Fe-N x species, large and accessible specific surface area of graphene and abundant active nitrogen atoms. When the C-rGO-ZIF catalyst was applied in the cathode of fuel cell, the power density can reach up to 301 mW cm-2, which highlights a practical application potential on small power supplies.

Facile synthesis of Pt-decorated Ir black as a bifunctional oxygen catalyst for oxygen reduction and evolution reactions.

Pt-Decorated Ir black (Pt@Ir) nanoparticles with two varying Pt mass fractions (Pt4@Ir96 and Pt16@Ir84) were generated by a facile method in water with the aid of Ir black. The Pt@Ir nanoparticles were investigated as a bifunctional oxygen catalysts for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in acidic medium. Benefiting from the good dispersion of ultrafine Pt nanodots on the Ir black surface and the synergistic effect between the Pt and underlying Ir atoms, Pt@Ir nanoparticles have exhibited outstanding ORR activity and comparable OER performance in comparison with commercial Ir black. In particular, Pt16@Ir84 shows an ORR mass activity of 2.6 times that of commercial Pt black and exhibits much better bifunctional performances than a mixture of Pt black and Ir black with a Ir/Pt mass ratio of 50/50 (Pt50Ir50). Our work highlights the effectiveness of decorating Ir black with Pt nanodots to fabricate bifunctional oxygen catalysts.

Quality Measurement and Improvement Study of Surgical Coronary Revascularization: Medication Adherence (MISSION-2).

BACKGROUND: Secondary preventive therapies play a key role in the prevention of adverse outcomes after coronary artery bypass grafting (CABG). However, medication adherence after CABG is often poor, and conventional interventions for improving adherence have limited success. With increasing penetration of smartphones, health-related smartphone applications might provide an opportunity to improve adherence. Carefully designed trials are needed to provide reliable evidence for the use of these applications in patients after CABG. METHODS: The Measurement and Improvement Studies of Surgical Coronary Revascularization: Medication Adherence (MISSION-2) study is a multicenter randomized controlled trial, aiming to randomize 1000 CABG patients to the intervention or control groups in a 1:1 ratio. We developed the multifaceted, patient-centered, smartphone-based Heart Health Application to encourage medication adherence in the intervention group through a health self-management program initiated during hospital admission for CABG. The application integrated daily scheduled reminders to take the discharge medications, cardiac educational materials, a dynamic dashboard to review cardiovascular risk factors and secondary prevention targets, and weekly questionnaires with interactive feedback. The primary outcome was secondary preventive medication adherence measured by the Chinese version of the 8-item Morisky Medication Adherence Scale at 6 months after randomization. Secondary outcomes included all-cause death, cardiovascular rehospitalization, and a composite of death, myocardial infarction, stroke, and repeat revascularization. DISCUSSION: Findings will not only provide evidence regarding the feasibility and effectiveness of the described intervention for improving adherence to CABG secondary preventive therapies but also explore a model for outpatient health self-management that could be translated to various chronic diseases and widely disseminated across resource-limited settings. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT02432469).

Identification and functional characterization of TNF receptor associated factor 3 in the sea cucumber Apostichopus japonicus.

TNF receptor associated factors (TRAFs) are a family of proteins primarily involved in both adaptive and innate immunity. In this study, we identified a novel TRAF3 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjTRAF3). The full-length of AjTRAF3 was of 2796 bp including a 5' untranslated region (UTR) of 83 bp, a 3' UTR of 1066 bp and a putative open reading frame of 1647 bp encoding a polypeptide of 548 amino acid residues. The representative domains such as a RING finger domain (residues 54-96), two TRAF domains with zinc finger structure (residues 141-228), a coiled coil and a meprin and TRAF homology (MATH) domain (residues 396-522) were all detected in the deduced amino acids of AjTRAF3. AjTRAF3 was ubiquitously expressed in all examined tissues with predominant expression in the body wall and slightly weaker in intestine, respiratory tree, tube feet, coelomocytes and longitudinal muscle. Time-course expression analysis in coelomocytes revealed that AjTRAF3 was significantly depressed towards Vibrio splendidus infection with a 0.20-fold decrease at 12 h, compared to control levels. AjTRAF3 silencing could elevate intracellular ROS levels by 2.08-fold and 2.09-fold compared to each control group in vitro and in vivo, respectively. Taken together, all these results suggested that AjTRAF3 may play a crucial role in the processes of anti-bacteria response in sea cucumber through regulating ROS production.