Three cassava A20/AN1 family genes, Metip3 (5, and 7), can bestow on tolerance of plants to multiple abiotic stresses but show functional convergence and divergence.

A20/AN1 zinc-finger domain-containing genes are very promising candidates in improving plant tolerance to abiotic stresses, but considerably less is known about functions and mechanisms for many of them. In this study, Metip3 (5, and 7), cassava (Manihot esculenta) A20/AN1 genes carrying one A20 domain and one AN1 domain, were functionally characterized at different layers. Metip3 (5, and 7) proteins were all located in the nucleus. No interactions were found between these three proteins. Metip3 (5, and 7)-expressing Arabidopsis was more tolerant to multiple abiotic stresses by Na, Cd, Mn, Al, drought, high temperature, and low temperature. Metip3- and Metip5-expressing Arabidopsis was sensitive to Cu stress, while Metip7-expressing Arabidopsis was insensitive. The H2O2 production significantly decreased in all transgenic Arabidopsis, however, O2·- production significantly decreased in Metip3- and Metip5-expressing Arabidopsis but did not significantly changed in Metip7-expressing Arabidopsis under drought. Metip3 (5, and 7) expression-silenced cassava showed the decreased tolerance to drought and NaCl, presented significant decreases in superoxide dismutase and catalase activities and proline content, and displayed a significant increase in malondialdehyde content under drought. Taken together with transcriptome sequencing analysis, it is suggested that Metip5 gene can not only affect signal transduction related to plant hormone, mitogen activated protein kinases, and starch and sucrose metabolism, DRE-binding transcription factors, and antioxidants, conferring the drought tolerance, but also might deliver the signals from DREB2A INTERACTING PROTEIN1, E3 ubiquitin-protein ligases to proteasome, leading to the drought intolerance. The results are informative not only for further study on evolution of A20/AN1 genes but also for development of climate resilient crops.

Characterization of ZmPMP3g function in drought tolerance of maize.

The genes enconding proteins containing plasma membrane proteolipid 3 (PMP3) domain are responsive to abiotic stresses, but their functions in maize drought tolerance remain largely unknown. In this study, the transgenic maize lines overexpressing maize ZmPMP3g gene were featured by enhanced drought tolerance; increases in total root length, activities of superoxide dismutase and catalase, and leaf water content; and decreases in leaf water potential, levels of O2-·and H2O2, and malondialdehyde content under drought. Under treatments with foliar spraying with abscisic acid (ABA), drought tolerance of both transgenic line Y7-1 overexpressing ZmPMP3g and wild type Ye478 was enhanced, of which Y7-1 showed an increased endogenous ABA and decreased endogenous gibberellin (GA) 1 (significantly) and GA3 (very slightly but not significantly) and Ye478 had a relatively lower ABA and no changes in GA1 and GA3. ZmPMP3g overexpression in Y7-1 affected the expression of multiple key transcription factor genes in ABA-dependent and -independent drought signaling pathways. These results indicate that ZmPMP3g overexpression plays a role in maize drought tolerance by harmonizing ABA-GA1-GA3 homeostasis/balance, improving root growth, enhancing antioxidant capacity, maintaining membrane lipid integrity, and regulating intracellular osmotic pressure. A working model on ABA-GA-ZmPMP3g was proposed and discussed.

MeGATAs, functional generalists in interactions between cassava growth and development, and abiotic stresses.

The proteins with DNA-binding preference to the consensus DNA sequence (A/T) GATA (A/G) belong to a GATA transcription factor family, with a wide array of biological processes in plants. Cassava (Manihot esculenta) is an important food crop with high production of starch in storage roots. Little was however known about cassava GATA domain-containing genes (MeGATAs). Thirty-six MeGATAs, MeGATA1 to MeGATA36, were found in this study. Some MeGATAs showed a collinear relationship with orthologous genes of Arabidopsis, poplar and potato, rice, maize and sorghum. Eight MeGATA-encoded proteins (MeGATAs) analysed were all localized in the nucleus. Some MeGATAs had potentials of binding ligands and/or enzyme activity. One pair of tandem-duplicated MeGATA17-MeGATA18 and 30 pairs of whole genome-duplicated MeGATAs were found. Fourteen MeGATAs showed low or no expression in the tissues. Nine analysed MeGATAs showed expression responses to abiotic stresses and exogenous phytohormones. Three groups of MeGATA protein interactions were found. Fifty-three miRNAs which can target 18 MeGATAs were identified. Eight MeGATAs were found to target other 292 cassava genes, which were directed to radial pattern formation and phyllome development by gene ontology enrichment, and autophagy by Kyoto Encyclopaedia of Genes and Genomes enrichment. These data suggest that MeGATAs are functional generalists in interactions between cassava growth and development, abiotic stresses and starch metabolism.

MeSWEET15a/b genes play a role in the resistance of cassava (Manihot esculenta Crantz) to water and salt stress by modulating sugar distribution.

The sugar transporter SWEET plays a role in plant growth, carbon allocation, and abiotic stress resistance. We examined the function of SWEET in cassava (Manihot esculenta Crantz) under water and salt stress. Bioinformatics, subcellular localization, yeast deficient complementation, and virus-induced gene silencing (VIGS) were used to examine the function of SWEET in cassava. Twenty-eight MeSWEETs genes were found based on the conserved domain MtN3/saliva of SWEET transporters, two MeSWEET15a/b of them were identified by phylogenetic analysis, which were located on the cell membrane. They transfer sucrose, fructose, glucose, and mannitol from culture media to yeast cells, predominately transferring sucrose via bleeding fluid saps in plant. Leaf sucrose content was increased in MeSWEET15a/b-silenced cassava plants, resulting in changes in carbon distribution, with an increase in starch accumulation in the leaves and a decrease in starch accumulation in the roots. The silencing of MeSWEET15a/b genes led to tolerance to water and salt stress, consistent with a high accumulation of osmolytes, and low lipid membrane peroxidation. Changes in sugar distribution increased the expression of MeTOR and MeE2Fa in pTRV2-MeSWEET15a and pTRV2-MeSWEET15b cassava leaves. MeSWEET15a/b acts as pivotal modulators of sugar distribution and tolerance to water and high salt stress in cassava.

Effects of high air temperature, drought, and both combinations on maize: A case study.

High air temperature (HAT) and natural soil drought (NSD) have seriously affected crop yield and frequently take place in a HAT-NSD combination. Maize (Zea mays) is an important crop, thermophilic but not heat tolerant. In this study, HAT, NSD, and HAT-NSD effects on maize inbred line Huangzao4 -were characterized. Main findings were as follows: H2O2 and O- accumulated much more in immature young leaves than in mature old leaves under the stresses. Lateral roots were highly distributed near the upper pot mix layers under HAT and near root tips under HAT-NSD. Saccharide accumulated mainly in stressed root caps (RC) and formed a highly accumulated saccharide band at the boundary between RC and meristematic zone. Lignin deposition was in stressed roots under NSD and HAT-NSD. Chloroplasts increased in number and formed a high-density ring around leaf vascular bundles (VB) under HAT and HAT-NSD, and sparsely scattered in the peripheral area of VBs under NSD. The RC cells containing starch granules were most under NAD-HAT but least under HAT. Under NSD and HAT-NSD followed by re-watering, anther number per tassel spikelet reduced to 3. These results provide multiple clues for further distinguishing molecular mechanisms for maize to tolerate these stresses.

Association between complete right bundle branch block and atrial fibrillation development.

BACKGROUND: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. METHODS: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). RESULTS: Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. CONCLUSION: Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.

Efficient removal of a low concentration of Pb(II), Fe(III) and Cu(II) from simulated drinking water by co-immobilization between low-dosages of metal-resistant/adapted fungus Penicillium janthinillum and graphene oxide and activated carbon.

Drinking water safety cannot be overemphasized. Filamentous fungi have many excellent features for metal removal. Both graphene oxide (GO) and activated carbon (AC) are conventional metal adsorbents, but they are not suitable for large-scale use due to high cost. In this study, a low dosage of conidia (2.0 × 104 conidia/mL) of metal-resistant/adapted filamentous fungus Penicillium janthinillum strain GXCR were co-immobilized with a low dosage of 0.5 mg/L GO or 0.5 mg/L AC by embedding in 2% polyvinyl alcohol (PVA)-3% sodium alginate (SA), generating six types of microbead adsorbents (MBAs) to remove metals from a low concentration of either single metal (100 mg/L) or mixed metals (100 mg/L each) of Pb (II), Fe (III) and Cu (II) in drinking water. Fungus GXCR-containing MBAs had higher specific surface areas (SSAs), better mesoporous structures, and a higher removal rate (85-98.99%) of single or mixed metals. Singl-metal adsorptions of MBAs were almost unaffected by temperature changes. MBAs showed a stable removal rate of 87-94% during four cycles of adsorption-desorption of single metal. Single-metal adsorptions were well described by multiple models of Freundlich isotherm with constant values of 0.21-0.432, Langmuir isotherm with constant values of 0.037-0.17, Pseudo-fist-order, Pseudo-second-order, and intra-particle diffusion (IPD). In conclusion, co-immobilization between GXCR, GO and AC can make metal removal more efficient. Adsorption capacity is increased with SSAs but not in the same proportion. Single-metal adsorptions involve multiple mechanisms of monolayer and multilayer adsorptions, external mass transfer, and IPD. IPD is important but not the only one rate-controlling step for single-metal adsorptions.

Effect of catheter ablation on clinical outcomes in patients with atrial fibrillation and significant functional mitral regurgitation.

BACKGROUND: In patients with atrial fibrillation (AF) and functional mitral regurgitation (MR), catheter ablation reduces the severity of MR and improves cardiac remodeling. However, its effects on prognosis are uncertain. METHODS: This retrospective study included 151 consecutive patients with AF and functional MR, 82 (54.3%) of whom were treated by catheter ablation (Ablation group) and 69 (45.7%) with drug therapy without ablation (Non-ablation group). Forty-three pairs of these patients were propensity matched on the basis of age, CHA2DS2-VASc scores, and left ventricular ejection fraction. The primary outcome evaluated was severity of MR, cardiac remodeling and the combined incidence of subsequent heart failure-related hospitalization and strokes/transient ischemic attacks. RESULTS: Patients in the Ablation group showed a significant decrease in the severity of MR (p < 0.001), a significant decrease in the left atrial diameter (p = 0.010), and significant improvement in the left ventricular ejection fraction (p = 0.015). However, patients in the Non-ablation group showed only a significant decrease in the severity of MR (p = 0.004). The annual incidence of the studied events was 4.9% in the Ablation group and 16.7% in the Non-ablation group, the incidence being significantly lower in the ablation than Non-ablation group (p = 0.026) according to Kaplan-Meier curve analyses. According to multivariate Cox regression analysis, catheter ablation therapy (hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.09-0.84; p = 0.024) and heart failure at baseline (HR 3.84, 95% CI 1.07-13.74; p = 0.038) were independent predictors of the incidence of the studied events. CONCLUSIONS: Among patients with AF and functional MR, catheter ablation was associated with a significantly lower combined risk of heart failure-related hospitalization and stroke than in a matched cohort of patients receiving drug therapy alone.

Analyses of open-access multi-omics data sets reveal genetic and expression characteristics of maize ZmCCT family genes.

Flowering in maize (Zea mays) is influenced by photoperiod. The CO, CO-like/COL and TOC1 (CCT) domain protein-encoding genes in maize, ZmCCTs, are particularly important for photoperiod sensitivity. However, little is known about CCT protein-encoding gene number across plant species or among maize inbred lines. Therefore, we analysed CCT protein-encoding gene number across plant species, and characterized ZmCCTs in different inbred lines, including structural variations (SVs), copy number variations (CNVs), expression under stresses, dark-dark (DD) and dark-light (DL) cycles, interaction network and associations with maize quantitative trait loci (QTLs) by referring to the latest v4 genome data of B73. Gene number varied greatly across plant species, more in polyploids than in diploids. The numbers of ZmCCTs identified were 58 in B73, 59 in W22, 48 in Mo17, and 57 in Huangzao4 for temperate maize inbred lines, and 68 in tropical maize inbred line SK. Some ZmCCTs underwent duplications and presented chromosome collinearity. Structural variations and CNVs were found but they had no germplasm specificity. Forty-two ZmCCTs responded to stresses. Expression of 37 ZmCCTs in embryonic leaves during seed germination of maize under DD and DL cycles was roughly divided into five patterns of uphill pattern, downhill-pattern, zigzag-pattern, └-pattern and ⅃-pattern, indicating some of them have a potential to perceive dark and/or dark-light transition. Thirty-three ZmCCTs were co-expressed with 218 other maize genes; and 24 ZmCCTs were associated with known QTLs. The data presented in this study will help inform further functions of ZmCCTs.

PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II by reducing TGF-ß1/Smads pathway activation.

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.

Effect of pulmonary vein isolation on atrial fibrillation recurrence after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Dark response genes: a group of endogenous pendulum/timing players in maize?

MAIN CONCLUSION: Maize has a set of dark response genes, expression of which is influenced by multiple factor and varies with maize inbred lines but without germplasm specificity. The response to photoperiod is a common biological issue across the species kingdoms. Dark is as important as light in photoperiod. However, further in-depth understanding of responses of maize (Zea mays) to light and dark transition under photoperiod is hindered due to the lack of understanding of dark response genes. With multiple public "-omic" datasets of temperate and tropical/subtropical maize, 16 maize dark response genes, ZmDRGs, were found and had rhythmic expression under dark and light-dark cycle. ZmDRGs 6-8 were tandemly duplicated. ZmDRGs 2, 13, and 14 had a chromosomal collinearity with other maize genes. ZmDRGs 1-11 and 13-16 had copy-number variations. ZmDRGs 2, 9, and 16 showed 5'-end sequence deletion mutations. Some ZmDRGs had chromatin interactions and underwent DNA methylation and/or m6A mRNA methylation. Chromosomal histones associated with 15 ZmDRGs were methylated and acetylated. ZmDRGs 1, 2, 4, 9, and 13 involved photoperiodic phenotypes. ZmDRG16 was within flowering-related QTLs. ZmDRGs 1, 3, and 6-11 were present in cis-acting expression QTLs (eQTLs). ZmDRGs 1, 4, 6-9, 11, 12, and 14-16 showed co-expression with other maize genes. Some of ZmDRG-encoded ZmDRGs showed obvious differences in abundance and phosphorylation. CONCLUSION: Sixteen ZmDRGs 1-16 are associated with the dark response of maize. In the process of post-domestication and/or breeding, the ZmDRGs undergo the changes without germplasm specificity, including epigenetic modifications, gene copy numbers, chromatin interactions, and deletion mutations. In addition to effects by these factors, ZmDRG expression is influenced by promoter elements, cis-acting eQTLs, and co-expression networks.

Decrypting tubby-like protein gene family of multiple functions in starch root crop cassava.

Tubby-like proteins (TLPs) are ubiquitous in eukaryotes and function in abiotic stress tolerance of some plants. Cassava (Manihot esculenta Crantz) is a high-yield starch root crop and has a high tolerance to poor soil conditions and abiotic stress. However, little is known about TLP gene characteristics and their expression in cassava. We identified cassava TLP genes, MeTLPs, and further analysed structure, duplication, chromosome localization and collinearity, cis-acting elements in the promoter regions and expression patterns of MeTLPs, and three-dimensional structure of the encoded proteins MeTLPs. In conclusion, there is a MeTLP family containing 13 members, which are grouped into A and C subfamilies. There are 11 pairs of MeTLPs that show the duplication which took place between 10.11 and 126.69 million years ago. Two MeTLPs 6 and 9 likely originate from one gene in an ancestral species, may be common ancestors for other MeTLPs and would most likely not be eligible for ubiquitin-related protein degradation because their corresponding proteins (MeTLPs 6 and 9) have no the F-box domain in the N-terminus. MeTLPs feature differences in the number from TLPs in wheat, apple, Arabidopsis, poplar and maize, and are highlighted by segmental duplication but more importantly by the chromosomal collinearity with potato StTLPs. MeTLPs are at least related to abiotic stress tolerance in cassava. However, the subtle differences in function among MeTLPs are predictable partly because of their differential expression profiles, which are coupled with various cis­acting elements existing in the promoter regions depending on genes.

Cassava AGPase genes and their encoded proteins are different from those of other plants.

MAIN CONCLUSION: Cassava AGPase and AGPase genes have some unique characteristics. ADP-glucose pyrophosphorylase (AGPase) is a rate-limiting enzyme for starch synthesis. In this study, cassava AGPase genes (MeAGP) were analyzed based on six cultivars and one wild species. A total of seven MeAGPs was identified, including four encoding AGPase large subunits (MeAGPLs 1, 2, 3 and 4) and three encoding AGPase small subunits (MeAGPSs 1, 2 and 3). The copy number of MeAGPs varied in cassava germplasm materials. There were 14 introns for MeAGPLs 1, 2 and 3, 13 introns for MeAGPL4, and 8 introns for other three MeAGPSs. Multiple conservative amino acid sequence motifs were found in the MeAGPs. There were differences in amino acids at binding sites of substrates and regulators among different MeAGP subunits and between MeAGPs and a potato AGPase small subunit (1YP2:B). MeAGPs were all located in chloroplasts. MeAGP expression was not only associated with gene copy number and types/combinations, regions and levels of the DNA methylation but was also affected by environmental factors with the involvement of various transcription factors in multiple regulation networks and in various cis-elements in the gene promoter regions. The MeAGP activity also changed with environmental conditions and had potential differences among the subunits. Taken together, MeAGPs differ in number from those of Arabidopsis, potato, maize, banana, sweet potato, and tomato.

Advanced interatrial block predicts recurrence of atrial fibrillation after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. HYPOTHESIS: We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. METHODS: This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12-lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P-wave duration of >120 ms and biphasic [±] morphology in the inferior leads. RESULTS: During the mean follow-up period of 30.9 ± 20.0 months (range, 2-71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event-free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2 DS2 -VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30-36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33-119.75; P = .027) as independent predictors of AF recurrence. CONCLUSIONS: Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.

Association Between CHADS2 Score and the Development of Interatrial Block.

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS2 scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS2 score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS2 score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS2 score of ≥ 2 with IAB compared with a CHADS2 score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS2 score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS2 score was significantly associated with the development of IAB in this study population.

Cyanidin ameliorates cisplatin-induced cardiotoxicity via inhibition of ROS-mediated apoptosis.

Oxidative stress and apoptosis serve an essential role in cisplatin-induced cardiotoxicity, which limits its clinical use, and increases the risk of cardiovascular disease. As a natural drug, the antioxidant and antitumor effects of cyanidin have been recognized, but its protective effect on cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with cisplatin (1-40 µM) in the presence or absence of cyanidin (40-80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that cyanidin was able to dose-dependently reverse cisplatin-induced cell damage and apoptosis, attenuate the accumulation of reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of caspase 3, caspase 9, but not caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in cisplatin-induced apoptosis. Cyanidin was able to block the translocation of Bax and reduce the release of cytochrome c from cytoplasm. These data indicate that cyanidin attenuates cisplatin-induced cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated kinase signaling pathways may also serve important roles.

Cordycepin inhibits vascular adhesion molecule expression in TNF-α-stimulated vascular muscle cells.

Atherosclerosis is a chronic inflammatory disease, which is associated with the increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Cordycepin is one of the major bioactive components of Ophiocordyceps sinensis that has been demonstrated to exert anti-atherogenic activity; however, its molecular mechanisms are poorly understood. The aim of the present study was to examine the in vitro effects of cordycepin on the tumor necrosis factor (TNF)-α-induced suppression of adhesion molecule expression. The results of the present study demonstrated that cordycepin markedly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in TNF-α-stimulated human aortic vascular smooth muscle cells (HA-VSMCs). Cordycepin significantly inhibited the TNF-α-induced mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) activation (P<0.05), markedly inhibited the TNF-α-induced expression level of nuclear factor (NF)-κB p65 and markedly prevented the TNF-α-associated degradation of IκBα in HA-VSMCs. The results of the present study suggest that cordycepin inhibits the expression of VCAM-1 and ICAM-1 in TNF-α-stimulated HA-VSMCs via downregulating the MAPK/Akt/NF-κB signaling pathway. Therefore, cordycepin may have a potential therapeutic application for preventing the advancement of atherosclerotic lesions.

Myricitrin inhibits vascular adhesion molecule expression in TNF­α­stimulated vascular smooth muscle cells.

Increased expression of adhesion molecules is thought to serve an important role in the pathogenesis of atherosclerosis. Myricitrin, a bioactive compound of Myrica cerifera, has been demonstrated to exhibit anti­atherogenic effects. However, the effect of myricitrin on the expression of adhesion molecules in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, the aim of the present study was to evaluate the inhibitory effects of myricitrin on tumor necrosis factor­α (TNF­α)­induced expression of adhesion molecules in VSMCs in vitro. The results revealed that myricitrin inhibited the adhesion of human THP­1 monocyte cells to TNF­α­stimulated mouse MOVAS­1 VSMC cells, and reduced the expression of adhesion molecules in TNF­α­stimulated MOVAS­1 cells. In addition, myricitrin significantly inhibited the TNF­α­induced expression of nuclear factor (NF)­κB p65, and prevented the TNF­α­induced degradation of nuclear factor of κ light chain enhancer in B­cells inhibitor α. Furthermore, myricitrin inhibited the production of intracellular reactive oxygen species in TNF­α­stimulated MOVAS­1 cells. In conclusion, the results of the present study indicated that myricitrin inhibits the expression of vascular cell adhesion protein­1 and intercellular adhesion molecule­1 in TNF­α­stimulated MOVAS­1 cells potentially via the NF­κB signaling pathway. Therefore, myricitrin may be an effective pharmacological agent for the prevention or treatment of atherosclerosis.

A proteomic-based investigation of potential copper-responsive biomarkers: Proteins, conceptual networks, and metabolic pathways featuring Penicillium janthinellum from a heavy metal-polluted ecological niche.

Filamentous fungi-copper (Cu) interactions are very important in the formation of natural ecosystems and the bioremediation of heavy metal pollution. However, important issues at the proteome level remain unclear. We compared six proteomes from Cu-resistant wild-type (WT) Penicillium janthinellum strain GXCR and a Cu-sensitive mutant (EC-6) under 0, 0.5, and 3 mmol/L Cu treatments using iTRAQ. A total of 495 known proteins were identified, and the following conclusions were drawn from the results: Cu tolerance depends on ATP generation and supply, which is relevant to glycolysis pathway activity; oxidative phosphorylation, the TCA cycle, gluconeogenesis, fatty acid synthesis, and metabolism are also affected by Cu; high Cu sensitivity is primarily due to an ATP energy deficit; among ATP generation pathways, Cu-sensitive and Cu-insensitive metabolic steps exist; gluconeogenesis pathway is crucial to the survival of fungi in Cu-containing and sugar-scarce environments; fungi change their proteomes via two routes (from ATP, ATP-dependent RNA helicases (ADRHs), and ribosome biogenesis to proteasomes and from ATP, ADRHs to spliceosomes and/or stress-adapted RNA degradosomes) to cope with changes in Cu concentrations; and unique routes exist through which fungi respond to high environmental Cu. Further, a general diagram of Cu-responsive paths and a model theory of high Cu are proposed at the proteome level. Our work not only provides the potential protein biomarkers that indicate Cu pollution and targets metabolic steps for engineering Cu-tolerant fungi during bioremediation but also presents clues for further insight into the heavy metal tolerance mechanisms of other eukaryotes.