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Stress hyperglycemia ratio (SHR) is associated with increased in-hospital morbidity and mortality in patients with acute myocardial infarction (AMI). We aimed to investigate the impact of stress "hyperglycemia" on long-term mortality after AMI in patients with and without diabetes mellitus (DM).We included 2089 patients with AMI between February 2014 and March 2018. SHR was measured with the fasting glucose divided by the estimated average glucose derived from glycosylated hemoglobin (HbA1c). The primary endpoint was all-cause death. Of 2 089 patients (mean age: 65.7 ± 12.4, 76.7% were men) analyzed, 796 (38.1%) had DM. Over a median follow-up of 2.7 years, 141 (6.7%) and 150 (7.2%) all-cause deaths occurred in the diabetic and nondiabetic cohorts, respectively. Compared with participants with low SHR (1.24 in DM;1.14 in non-DM), the hazard ratios and 95% confidence intervals for those with high SHR (≥1.24 in DM; ≥1.14 in non-DM) for all-cause mortality were 2.23 (1.54-3.23) and 1.79 (1.15-2.78); for cardiovascular mortality were 2.42 (1.63-3.59) and 2.10 (1.32-3.35) in DM and non-DM subjects, respectively. The mortality prediction was improved in the diabetic individuals with the incorporation of SHR into the Global Registry of Acute Coronary Events (GRACE) score, showing an increase in a continuous net reclassification index of 0.184 (95%CI: 0.003-0.365) and an absolute integrated discrimination improvement of 0.014 (95%CI: 0.002-0.025).The improvement in the prediction of long-term mortality beyond the GRACE score indicates the potential of SHR as a biomarker for post-MI risk stratification among patients with DM.NCT03533543.

Oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction exerts an essential role in the development of atherosclerosis. Protein Z-dependent protease inhibitor (ZPI), a member of the serine protease inhibitor superfamily, could inhibit the function of activated coagulation factor X (FXa) via interaction with protein Z (PZ). Studies have pointed out that ZPI was statistically related to atherosclerotic diseases, which may have a robust cardiovascular protective effect. However, the underlying mechanism of ZPI on ox-LDL-mediated endothelial injury requires further elucidation. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 μg/ml) and ZPI (10 μg/ml). Cell viability was measured by the Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis, oxidative stress, and endothelial-to-mesenchymal transition (EndMT) were analyzed by immunofluorescence (IF). Cell migration was measured using a wound-healing assay. Quantitative real-time polymerase chain reaction and western blot analysis were performed to determine messenger RNA and protein expression. Ox-LDL (100 μg/ml, 48 h) significantly reduced cell viability and migration, increased EndMT, inflammation, apoptosis, and oxidative stress. The related protein expression of phosphatidylinositol 3 kinase/protein kinase B (Pi3k/Akt) signal pathway in HUVECs was also simultaneously decreased. We also discovered that ZPI treatment could prevent ox-LDL-mediated endothelial injury through the improvement of cell viability and alleviation of apoptosis, oxidative stress, EndMT, and inflammation. Thus, the protective effect of ZPI on HUVECs may be mediated by activation of the Pi3k/Akt signal pathway. ZPI may exert an important protective role in HUVECs dysfunction triggered by ox-LDL via activation of the Pi3k/Akt signal pathway. Therefore, ZPI may possess potential therapeutic effects on atherosclerotic endothelial injury-related diseases.

Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-α), and high-mobility group box-1 (HMGB1) contributes to the regulation of inflammation and angiogenesis in multiple physiological and pathophysiological settings. Here, we present evidence of an overriding role for miR-126 in the regulation of HMGB1 and its downstream proinflammatory effectors in endothelial cells subjected to hypoxia with concurrent acidosis (H/A). Methods. Primary mouse endothelial cells (PMEC) were exposed to hypoxia or H/A to simulate short or chronic low-flow ischemia, respectively. RT-qPCR quantified mRNA transcripts, and proteins were measured by western blot. ROS were quantified by fluorogenic ELISA and luciferase reporter assays employed to confirm an active miR-126 target in the HMGB1 3 ′ UTR. Results. Enhanced expression of miR-126 in PMECs cultured under neutral hypoxia was suppressed under H/A, whereas the HMGB1 expression increased sequentially under both conditions. Enhanced expression of HMGB1 and downstream inflammation markers was blocked by the premiR-126 overexpression and optimized by antagomiR. Compared with neutral hypoxia, H/A suppressed the HIF-1α expression independently of miR-126. The results show that HMGB1 and downstream effectors are optimally induced by H/A relative to neutral hypoxia via crosstalk between hypoxia signaling, miR-126, and HIF-1α, whereas B-cell lymphoma 2(Bcl2), a HIF-1α, and miR-126 regulated gene expressed optimally under neutral hypoxia. Conclusion. Inflammatory responses of ECs to H/A are dynamically regulated by the combined actions of hypoxia, miR-126, and HIF-1α on the master regulator HMGB1. The findings may be relevant to vascular diseases including atherosclerotic occlusion and interiors of plaque where coexisting hypoxia and acidosis promote inflammation as a defining etiology.

Lesion mimic mutants resembling the hypersensitive response without pathogen attack are an ideal material to understand programmed cell death, the defence response, and the cross‐talk between defence response and development in plants. In this study, mic, a lesion mimic mutant from cultivar Yunyin treated with ethyl methanesulphonate (EMS), was screened. By map‐based cloning, a short‐chain alcohol dehydrogenase/reductase with an atypical active site HxxxK was isolated and designated as SDR7‐6. It functions as a homomultimer in rice and is localized at the endoplasmic reticulum. The lesion mimic phenotype of the mutant is light‐dependent. The mutant displayed an increased resistance response to bacterial blight, but reduced resistance to rice blast disease. The mutant and knockout lines showed increased reactive oxygen species, jasmonic acid content, antioxidant enzyme activity, and expression of pathogenicity‐related genes, while chlorophyll content was significantly reduced. The knockout lines showed significant reduction in grain size, seed setting rate, 1000‐grain weight, grain weight per plant, panicle length, and plant height. SDR7‐6 is a new lesion mimic gene that encodes a short‐chain alcohol dehydrogenase with atypical catalytic site. Disruption of SDR7‐6 led to cell death and had adverse effects on multiple agricultural characters. SDR7‐6 may act at the interface of the two defence pathways of bacterial blight and rice blast disease in rice., SDR7‐6, a short‐chain alcohol dehydrogenase/reductase family protein, negatively regulates cell death and the defence response to rice bacterial blight, but positively regulates the defence response to Magnaporthe oryzae.

Rice ( Oryza sativa L.) is a staple food in the world as well as an important monocotyledonous model plant for molecular biology, which has a long history of cultivation and domestication. However, many diseases will break out during rice production. For example, the rice blast is the most destructive disease, which can cause the heavy loss or even total crop failure. Therefore, there are constant demands to cultivate durably blast-resistant varieties and identify more broad-spectrum blast resistance genes. Besides, it’s also very significant for agricultural production to elucidate the process and mechanism of immune response during the rice blast infection. The whole-genome sequencing of the resistant and susceptible near-isogenic lines derived from the broad-spectrum blast resistance Japonica Variety Yunyin and the universally blast-susceptible variety Lijiangxintuanheigu (LTH) was completed. Eight differential genes were screened from the Go terms that were associated with the immune response based on the whole-genome sequence data. We analyzed their gene structure, evolution and sequence variability between the resistant and susceptible near-isogenic lines. The results indicated that the homology of these protein sequences was between 55% and 80%, and the conserved protein domain analysis showed that most of them contained different numbers and types of leucine-rich repeat domains, a transmembrane domain and a C-terminal kinase domain, which were typical leucine-rich repeat receptor-like protein kinases. Moreover, they are all located within a cluster of chromosome 11 and were homologous to the bacterial blight resistance gene Xa21 . The leucine-rich repeat receptor-like protein kinases (LRR-RLKs) genes are a large conserved superfamily during the plant evolution. In Arabidopsis , there are 14 subfamilies and more than 200 members of LRR-RLKs were identified, whereas the rice genome contained more than 900 LRR-RLKs genes. The perception and recognition of pathogen infection are mainly mediated by the plant cells surface pattern-recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors. PRRs contain many receptor kinases including the leucine-rich repeat receptor-like protein kinases, which play an important role in the signal transduction during the plant development, immune response and sense of the environmental changes. In order to further explore the potential function of these genes during the rice blast disease response, the rice seedlings were inoculated with Magnaporthe oryzae by spray and punch methods and then the expression pattern of these genes during the fungal infection were analyzed by qRT-PCR. The results showed that some genes response to the blast disease. Thus, we speculated that some of them might be involved in the rice blast disease response. This study laid a foundation for further studying genes related to the rice blast disease response.

Plants usually keep resistance (R) proteins in a static state under normal conditions to avoid autoimmunity and save energy for growth, but R proteins can be rapidly activated upon perceiving pathogen invasion. Pib, the first cloned blast disease R gene in rice, encoding a nucleotide-binding leucine-rich repeat (NLR) protein, mediates resistance to the blast fungal (Magnaporthe oryzae) isolates carrying the avirulence gene AvrPib. However, the molecular mechanisms about how Pib recognizes AvrPib and how it is inactivated and activated remain largely unclear. In this study, through map-based cloning and CRISPR-Cas9 gene editing, we proved that Pib contributes to the blast disease resistance of rice cultivar Yunyin (YY). Furthermore, an SH3 domain-containing protein, SH3P2, was found to associate with Pib mainly at clathrin-coated vesicles in rice cells, via direct binding with the coiled-coil (CC) domain of Pib. Interestingly, overexpression of SH3P2 in YY compromised Pib-mediated resistance to M. oryzae isolates carrying AvrPib and Pib-AvrPib recognition-induced cell death. SH3P2 competitively inhibits the self-association of the Pib CC domain in vitro, suggesting that binding of SH3P2 with Pib undermines its homodimerization. Moreover, SH3P2 can also interact with AvrPib and displays higher affinity to AvrPib than to Pib, which leads to dissociation of SH3P2 from Pib in the presence of AvrPib. Taken together, our results suggest that SH3P2 functions as a "protector" to keep Pib in a static state by direct interaction during normal growth but could be triggered off by the invasion of AvrPib-carrying M. oryzae isolates. Our study reveals a new mechanism about how an NLR protein is inactivated under normal conditions but is activated upon pathogen infection.

The induction of embryogenic calli plays a vital role in the genetic transformation and regeneration of rice (Oryza sativa L.). Despite progress in rice tissue culture, the molecular mechanisms of embryogenic callus induction remain unknown. In this study, gene expression profiles associated with calli were comprehensively analyzed during callus induction of japonica rice ‘Yunyin’. We first confirmed that NMB medium with 24 h of light and 0 h of dark (NMB-L) was the optimal condition for ‘Yunyin’ callus induction, while J3 medium with 0 h of light and 24 h of dark (J3-D) was the worst condition. After transcriptome analysis, 33,597 unigenes were assembled, among which we identified 6,063 DEGs (Differentially Expressed Genes) related to media and seven DEGs related to photoperiod. Phenylpropanoid biosynthesis, plant hormone signal, and starch and sucrose metabolism were the top three pathways affected by media, while the circadian rhythm-plant pathway was associated with photoperiod. Furthermore, we identified two candidate genes, Os01g0965900 and Os12g0555200, affected by both medium and photoperiod. Statistical analysis of RNA-seq libraries showed that the expression levels of these two genes in J3-D calli were over 2.5 times higher than those in NMB-L calli, which was further proved by RT-qPCR analysis. Based on FPKM (Fragments Per Kilobase of transcript Per Million mapped reads), unigenes belonging to the NMB-L group were mainly assigned to ribosome, carbon metabolism, biosynthesis of amino acids, protein processing in endoplasmic reticulum, and plant hormone signal transduction pathways. We transformed Os12g0555200(Nip) and Os12g0555200(9311) into ‘Nipponbare’ calli and observed their effects on the growth and development process of rice calli using TEM (Transmission Electron Microscopy) and SEM (Scanning Electron Microscopy). Observations showed that Os12g0555200(9311) was more disadvantageous to rice callus growth than Os12g0555200(Nip). Our results reveal that the Os12g0555200, identified from transcriptomic profiles, has a negative influence during ‘Yunyin’ callus induction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-022-01283-y.

Aims New‐onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on heart failure (HF) is still not well characterized. We aimed to investigate the relationship between NOAF complicating AMI and HF hospitalization. Methods and results Adult AMI patients identified in the New‐Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in Shanghai registry who, discharged alive, had complete echocardiography and follow‐up data from February 2014 to March 2018 were included. Patients were divided according to the presence of NOAF. The outcome measures were HF hospitalization and death during the observational period (until 10 April 2019). Cox proportional hazard models were performed in the whole population and propensity score‐matched (PSM) cohort to assess the adjusted hazard ratio (HR) and 95% confidence interval (CI). Overall, 2075 patients (mean age: 65.2 ± 12.3 years, 77.3% were men) with AMI were analysed, of whom 228 (11.0%) developed NOAF. Advanced age, admission HF (Killip II–IV), impaired renal function, decreased left ventricular ejection fraction, increased heart rate, and left atrial enlargement were independent predictors of NOAF. Over a median observational period of 2.7 years, the annual incidence rates of HF hospitalization were 18.4% and 2.8% for patients with NOAF and sinus rhythm, respectively. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (HR: 3.14, 95% CI: 2.30–4.28, P

Aims We aimed to investigate the prognostic impact of the burden of new-onset atrial fibrillation (NOAF) on long-term cardiovascular outcomes in patients with acute myocardial infarction (AMI). Methods and results This retrospective analysis consecutively included patients without a documented atrial fibrillation (AF) history who admitted for AMI at Shanghai Tenth People’s Hospital between February 2014 and March 2018. Atrial fibrillation burden was measured as the percentage of time spent in AF, and its optimal cut-off value of 10.87% was identified by X-tile software. Of 2399 patients (mean age: 65.8 years, 76.6% of men), 278 (11.6%) developed NOAF during hospitalization. During a median follow-up of 2.7 years, the incidence of all-cause death was 3.19, 9.00, and 17.41 per 100 person-years in the sinus rhythm (SR), low-burden (AF burden ≤ 10.87%), and high-burden (AF burden > 10.87%) groups, respectively. After adjustment for confounders, it was the high-burden NOAF [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.28–2.95] rather than the low-burden one (HR: 1.47, 95% CI: 0.97–2.21) that was significantly associated with increased mortality compared with SR. Concordant results were obtained in our propensity score-matched analyses [2.55 (1.57–4.16) and 1.32 (0.85–2.05) for high- and low-burden NOAF, respectively). In addition, post-myocardial infarction NOAF was associated with an increased risk of heart failure irrespective of its burden. Only those high-burden individuals were at heightened risk of ischaemic stroke. The restricted cubic spline curves illustrated a dose-response relationship of NOAF burden with outcomes. Conclusion In patients with NOAF complicating AMI, high AF burden was strongly associated with long-term outcomes.

Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.

Thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) is reported to improve myocardial reperfusion. However, the long-term prognostic implication of TA remains unclear. We aimed to investigate the influence of adjunctive TA on long-term outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing PPCI. All STEMI patients from China that included in the TOTAL trial who were ≥18 years old and referred for PPCI within the 12 hours after symptom onset between January 2011 and November 2012 were retrospectively analyzed. Patients were divided into 2 groups based on the use of TA or not. The primary efficacy outcomes were 5-year major adverse cardiac events, a composite of cardiovascular death, recurrent MI, cardiogenic shock, or heart failure hospitalization. The primary safety outcome was a 5-year stroke. A total of 563 patients were included. The incidence rate of major adverse cardiac events at 5 years in the TA group was similar to that in the PCI group (hazard ratio [HR] 0.70; 95% confidence interval [CI] 0.42 to 1.17). In addition, TA was significantly associated with a nearly sevenfold increased risk of stroke at 5 years compared with PCI alone (HR 7.32, 95% CI 1.33 to 40.31). Our propensity scoring match analyses suggested that patients with an occluded lesion might benefit from the TA (HR 0.24, 95% CI 0.08 to 0.70). In conclusion, TA is not associated with improved outcomes in patients with STEMI but may have an adverse impact on stroke. Patients with an occluded infarct-related artery could benefit from the TA.

Oryza sativa SPL14 (OsSPL14), identified as the IDEAL PLANT ARCHITECTURE1 or WEALTHY FARMER’S PANICLE gene, plays a critical role in regulating rice plant architecture. Here, OsSPL14-overexpression transgenic rice plants had shorter growth periods, short narrow flag leaves, and thick green leaves compared with wild type ‘MH86’ plants (WT). Additionally, transgenic lines had higher chlorophyll a (Chl a), chlorophyll b (Chl b), and carotenoid (Car x) contents at both seedling and mature stages. Expression of OsSPL14 increased at transcriptional level, and OsSPL14 protein level was substantially increased in transgenic lines relative to WT. A transcriptome analysis identified 473 up-regulated and 103 down-regulated genes in the transgenic plants. The expression of differentially expressed genes (DEGs) involved in carotenoid biosynthesis, abscisic acid (ABA) metabolism, and lignin biosynthesis increased significantly. Most of DEGs participated in “plant hormone signal transduction” and “starch and sucrose metabolism” were also up-regulated in the transgenic plants. In addition, there were higher ABA and gibberellin acid 3 (GA3) levels in OsSPL14-overexpression rice plants at seedling and tillering stages compared with WT. In contrast with that of WT, lignin and cellulose contents of culm increased distinctly. Also, silicon and potassium contents increased dramatically in transgenic lines. Meanwhile, the chalkiness ratios and chalkiness degrees decreased, and the gel consistency levels improved in transgenic lines. Thus, overexpression of OsSPL14 influenced growth period, leaf development, hormonal levels, culm composition, and grain quality characters of rice, which provides more insight into the function of OsSPL14.

Chuanzhen Hao,&ast; Jiachen Luo,&ast; Baoxin Liu,&ast; Wei Xu, Zhiqiang Li, Mengmeng Gong, Xiaoming Qin, Beibei Shi, Yidong Wei Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yidong Wei, Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Tel +86-21-66307249, Fax +86-21-66301771, Email ywei@tongji.edu.cnPurpose: The prognostic impact of new-onset atrial fibrillation (NOAF) among different heart failure (HF) subtypes including HF with preserved (HFpEF, ejection fraction [EF] ≥ 50%), mid-range (HFmrEF, EF 40%∼ 49%), and reduced (HFrEF, EF < 40%) EF following acute myocardial infarction (AMI) remains unclear. We aimed to investigate the incidence and prognostic implication of post-MI NOAF across HF subtypes.Patients and Methods: We included 1413 patients with post-MI HF (743 with HFpEF, 342 with HFmrEF and 328 with HFrEF) between February 2014 and March 2018. NOAF was considered as patients without a preexisting AF who developed AF during the AMI hospitalization. The primary endpoint was all-cause mortality.Results: Of 1413 patients (mean age 66.8 ± 12.6 years, 72.9% men) analyzed, 200 (14.2%) developed post-MI NOAF. Patients with HFrEF were more likely to experience NOAF compared to those with HFmrEF or HFrEF (18.9%, 13.7% and 12.2% in HFrEF, HFmrEF and HFpEF, respectively; p for trend = 0.006). During a median follow-up of 28.5 months, 192 patients died (70 with HFrEF, 35 with HFmrEF and 87 with HFpEF) and 195 patients experienced HF rehospitalization (79 with HFrEF, 37 with HFmrEF and 79 with HFpEF). After multivariable adjustment, NOAF was independently associated with all-cause mortality (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.03– 3.12) only in the HFrEF group compared to sinus rhythm (SR), whereas an increased risk of HF rehospitalization was found in all HF subtypes, particularly in HFmrEF (HR: 5.08, 95% CI: 2.29– 11.25) and HFpEF (HR: 2.83 95% CI: 1.64– 4.90).Conclusion: In patients with post-MI HF, NOAF carried a worse prognosis for all-cause death in the HFrEF group and for HF rehospitalization in all HF subtypes.Keywords: heart failure, acute myocardial infarction, atrial fibrillation, left ventricular ejection fraction, mortality

We identified a typical rice premature senescence leaf mutant 86 (psl86) and exhibited the first global ubiquitination data during rice leaf senescence. Premature leaf senescence affects the yield and quality of rice, causing irreparable agricultural economic losses. In this study, we reported a rice premature senescence leaf mutant 86 (psl86) in the population lines of rice (Oryza sativa) japonica cultivar 'Yunyin' (YY) mutagenized using ethyl methane sulfonate (EMS) treatment. Immunoblotting analysis revealed that a higher ubiquitination level in the psl86 mutant compared with YY. Thus, we performed the proteome and ubiquitylome analyses to identify the differential abundance proteins and ubiquitinated proteins (sites) related to leaf senescence. Among 885 quantified lysine ubiquitination (Kub) sites in 492 proteins, 116 sites in 94 proteins were classified as up-regulated targets and seven sites in six proteins were classified as down-regulated targets at a threshold of 1.5. Proteins with up-regulated Kub sites were mainly enriched in the carbon fixation in photosynthetic organisms, glycolysis/gluconeogenesis and the pentose phosphate pathway. Notably, 14 up-regulated Kub sites in 11 proteins were enriched in the carbon fixation in photosynthetic organism pathway, and seven proteins (rbcL, PGK, GAPA, FBA5, ALDP, CFBP1 and GGAT) were down-regulated, indicating this pathway is tightly regulated by ubiquitination during leaf senescence. To our knowledge, we present the first global data on ubiquitination during rice leaf senescence.

The Supplementary Materials of the manuscript entitled as "Prognostic significance of stress hyperglycemia in acute myocardial infarction patients with and without diabetes mellitus: data from the NOAFCAMI-SH registry"

Background: New-onset atrial fibrillation (NOAF) is a common complication during acute myocardial infarction (AMI) and sometimes can be completely asymptomatic, but the clinical implications of these asymptomatic episodes require further characterization. The objective of this study was to investigate the short- and long-term prognostic impact of post-MI NOAF based on the presence of AF-related symptoms.Methods: The New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai (NOAFCAMI-SH) registry was a retrospective cohort including participants with AMI without a documented history of AF. Patients with NOAF were divided into two groups according to the AF-related symptoms. The primary endpoint was all-cause mortality.Results: Of 2,399 patients included, 278 (11.6%) developed NOAF of whom 145 (6.0%) with asymptomatic episodes and 133 (5.5%) with symptomatic ones. During hospitalization, 148 patients died [106, 10, and 32 in the sinus rhythm (SR), asymptomatic, and symptomatic NOAF groups, respectively]. After multivariable adjustment, only symptomatic NOAF was associated with in-hospital mortality [odds ratio (OR): 2.32, 95% confidence interval (CI): 1.36–3.94] compared with SR. Over a median follow-up of 2.7 years, all-cause mortality was 3.2, 12.4, and 11.8% per year in the SR, asymptomatic, and symptomatic NOAF groups, respectively. After adjustment for confounders, it was the asymptomatic NOAF [hazard ratio (HR): 1.61, 95% CI: 1.09–2.37) rather than the symptomatic one (HR: 1.37, 95% CI: 0.88–2.12) that was significantly related to mortality. Similar results were also observed for cardiovascular mortality [HRs and 95% CI were 1.71 (1.10–2.67) and 1.25 (0.74–2.11) for asymptomatic and symptomatic NOAF, respectively]. Both asymptomatic and symptomatic NOAF episodes were associated with heart failure, whereas only those with symptomatic NOAF were at heightened risk of ischemic stroke. Our exploratory analysis further identified patients with asymptomatic high-burden NOAF as the highest-risk population (mortality: 19.6% per year).Conclusion: Among patients with AMI, symptomatic NOAF is related to in-hospital mortality and asymptomatic NOAF is associated with poor long-term survival.Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT03533543.

The glycosyltransferase 64 (GT64) family is widely conserved in many species, including animals and plants. The functions of GT64 family genes in animals have been well characterized in the biosynthesis of extracellular heparan sulfate, whereas two GT64 members in Arabidopsis thaliana are involved in the glycosylation of plasma membrane glycosylinositol phosphorylceramides (GIPCs). GIPCs are the main components of plant sphingolipids and serve as important signal molecules in various developmental processes and stress responses. Rice (Oryza sativa), a model monocot plant, contains four GT64 members in its genome. Using phylogenetic analysis, 73 GT64s from 19 plant species were divided into three main groups. Each group can be represented by the three members in Arabidopsis and show a trend of monocot-eudicot divergence. A promoter and genomic variation analysis of GT64s in rice showed that various stress-related regulatory elements exist in their promoters, and many sequence variations were found between the two main rice subspecies, japonica and indica. Additionally, transmembrane domain and subcellular localization analyses revealed that these genes all encode membrane-bound glycosyltransferases and are localized to the Golgi apparatus. Finally, expression analysis of the four GT64 genes in rice, as assessed by quantitative real-time PCR, showed that they have distinct tissue-specific expression patterns and respond to different hormone treatments or abiotic stresses. Our results indicated that this family of genes may play a role in different stress responses and hormone signaling pathways in rice, which will provide fundamental information for further investigation of their functions in future.

Chomsky is an evolutionary figure in linguistics. His greatest contribution lies in transformational generative grammar, which put an end to the leading position structuralism had held in language for more than 30 years. His naturalistic methodology has greatly influenced the research of both linguistics and psychology, and he is also considered to be the first to study language from the cognitive perspective. He insists on a naturalistic methodology; therefore, he was even considered by some to be a physicalist. However, this is not the case. On the contrary, TGG, as a critique of the behaviorist view of language, is intertwined with a critique of physicalism. On the one hand, he thinks the mind, like chemical elements and electrons, can be approached from a third-person perspective; on the other hand, he again admits there exists consciousness, which can be merely approached in terms of a first-person authority, which, therefore, is a fatal challenge to his core theory. Now there remains a new solution to this dilemma, that is, to admit that the mind is a special natural phenomenon with two means of existence: one is involved in physical aspects with the brain, and the other is concerned with something mental, with the former approached by a third-person perspective and the latter better researched via a first-person authority.

Many studies indicated postprandial hyperglycemia was closely related to the development of diabetes and the risk of cardiovascular disease. Acarbose was shown to delay the onset of diabetes in people with impaired glucose tolerance that was at low cardiovascular risk. The Acarbose Cardiovascular Evaluation (ACE) trial formally evaluated whether acarbose could reduce the frequency of cardiovascular events in patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of Type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation trial represented that acarbose did not reduce the risk of Major Adverse Cardiovascular Events (MACE), but the risk of new-onset diabetes by 18% for a median of 5.0 years follow-up.

This study shows that microRNA-320 (miR-320) is associated with many important cell functions, including cell differentiation, proliferation, migration, and apoptosis. However, the role of miR-320 in vascular smooth muscle cells (VSMCs) and proliferative vascular diseases is still completely unclear. In our study, we found that the expression of miR-320 in human VSMCs after PDGF stimulation was significantly down-regulated in time- and dose-dependent manner. Function analyses identified that miR-320 could inhibit the proliferation and migration of VSMCs in both basal and PDGF-stimulated conditions. Furthermore, Neuropilin 1 (NRP1) was demonstrated as a direct target of miR-320 in Luciferase reporter assays and miR-320 overexpression inhibited the expression of NRP1 with or without PDGF treatment. Finally, miR-320 was markedly decreased in mice carotid arteries after ligated injury, while the restoration of miR-320 via Ad-miR-320 attenuated neointimal hyperplasia by declining the NRP1 expression. The results confirmed that miR-320 regulated proliferation and migration of VSMCs and neointimal formation by targeting NRP1. These novel findings implied that the regulation of NRP1 expression by miR-320 has important significance in the early diagnosis and treatment of proliferation vascular diseases.

Baoxin Liu,1,* Jiachen Luo,1,* Mengmeng Gong,1 Zhiqiang Li,1 Beibei Shi,1 Xingxu Zhang,1 Xinqiang Han,2 Yidong Wei1 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Electrophysiology and Arrhythmia Services, Reid Health, Indiana University School of Medicine, Richmond, IN, 47374, USA*These authors contributed equally to this workCorrespondence: Yidong WeiDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Jingan District, Shanghai, People’s Republic of ChinaTel +86-021-66307249Fax +86-021-66301771Email ywei@tongji.edu.cnPurpose: LAAO has been an alternative therapy to oral anticoagulants (OACs) for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF) with elevated CHA2DS2-Vasc score, but the long-term outcomes of LAAO and its impacts on cardiac electrical and mechanical remodeling remain to be learned. We aimed to describe the impact of left atrial appendage occlusion (LAAO) on atrial remodeling and cardiovascular outcomes within 5-year follow-up.Patients and Methods: A total of 107 patients with nonvalvular atrial fibrillation (NVAF) undergoing LAAO in the Shanghai Tenth People’s Hospital between January 2014 and July 2017 were included. All participants were followed for ECG, transthoracic echocardiography (TTE), and clinical outcomes (including cardiovascular death, heart failure, ischemic stroke/systemic embolism, and pericardial effusion) at 6 and 12 months, and thereafter every 12 months after LAAO discharge until 5 years.Results: After LAAO, the left atrial diameter significantly increased at 6 months (48.6 ± 6.7 vs 46.5 ± 7.0 mm); heart rate decreased immediately after the procedure (78.5 ± 14.7 vs 85.3 ± 21.7 bpm) when compared with the pre-procedure level. The QTc interval prolongated to the highest value of 460.7 ± 46.8 ms at 6 months (pre-procedure level of 433.7± 49.0 ms). All these changes return to the pre-procedure level within the follow-up. For clinical outcomes, 51 patients suffered the composite of cardiovascular death (n=4, 3.7%), heart failure (n=25, 23.4%), ischemic stroke/systemic embolism (n=22, 20.6%), and pericardial effusion (n=26, 26.2%).Conclusion: LAAO did not change ECG or TTE characteristics and nonprocedure-related pericardial effusion is common during long-term follow-up. Further studies are warranted to investigate the optimal time frame of anticoagulation in patients undergoing LAAO.Keywords: atrial fibrillation, left atrial appendage occlusion, ECG, echocardiogram

Seed storability is a main agronomically important trait to assure storage safety of grain and seeds in rice. Although many quantitative trait loci (QTLs) and associated genes for rice seed storability have been identified, the detailed genetic mechanisms of seed storability remain unclear in rice. In this study, a genome-wide association study (GWAS) was performed in 456 diverse rice core collections from the 3K rice genome. We discovered the new nine QTLs designated as qSS1-1, qSS1-2, qSS2-1, qSS3-1, qSS5-1, qSS5-2, qSS7-1, qSS8-1, and qSS11-1. According to the analysis of the new nine QTLs, our results could well explain the reason why seed storability of indica subspecies was superior to japonica subspecies in rice. Among them, qSS1-2 and qSS8-1 were potentially co-localized with a known associated qSS1/OsGH3-2 and OsPIMT1, respectively. Our results also suggest that pyramiding breeding of superior alleles of these associated genes will lead to new varieties with improved seed storability in the future.

Background Phosphoenolpyruvate carboxylase (PEPC) plays an important role in the primary metabolism of higher plants. Several studies have revealed the critical importance of PEPC in the interaction of carbon and nitrogen metabolism. However, the function mechanism of PEPC in nitrogen metabolism is unclear and needs further investigation. Results This study indicates that transgenic rice expressing the sugarcane C4-PEPC gene displayed shorter primary roots and fewer crown roots at the seedling stage. However, total nitrogen content was significantly higher in transgenic rice than in wild type (WT) plants. Proteomic analysis revealed that there were more differentially expressed proteins (DEPs) responding to nitrogen changes in transgenic rice. In particular, the most enriched pathway “glutathione (GSH) metabolism”, which mainly contains GSH S-transferase (GST), was identified in transgenic rice. The expression of endogenous PEPC, GST and several genes involved in the TCA cycle, glycolysis and nitrogen assimilation changed in transgenic rice. Correspondingly, the activity of enzymes including GST, citrate synthase, 6-phosphofructokinase, pyruvate kinase and ferredoxin-dependent glutamate synthase significantly changed. In addition, the levels of organic acids in the TCA cycle and carbohydrates including sucrose, starch and soluble sugar altered in transgenic rice under different nitrogen source concentrations. GSH that the substrate of GST and its components including glutamic acid, cysteine and glycine accumulated in transgenic rice. Moreover, the levels of phytohormones including indoleacetic acid (IAA), zeatin (ZT) and isopentenyladenosine (2ip) were lower in the roots of transgenic rice under total nutrients. Taken together, the phenotype, physiological and biochemical characteristics of transgenic rice expressing C4-PEPC were different from WT under different nitrogen levels. Conclusions Our results revealed the possibility that PEPC affects nitrogen metabolism through regulating GST, which provide a new direction and concepts for the further study of the PEPC functional mechanism in nitrogen metabolism.

The pathogenesis of acute myocardial infarction (AMI) is associated with cardiomyocyte necrosis and apoptosis. Numerous studies have determined the regulatory effects of Phosphatase and tensin homolog (PTEN) cell proliferation and apoptosis in other cell types. However, the potential role of PTEN in cardiomyocyte is unclear. In this study, we used H9c2 cells cultured under serum deprivation to simulate the apoptosis process of myocardial infarction. Small interference RNA (siRNA) of PTEN was used to knock down the expression of PTEN. Cell viability was determined by CCK-8. Cell proliferation was examined by Edu staining, and the protein expression was analyzed by Western blot. We also evaluated the generation of ROS, the degree of DNA damage, and cell apoptosis using immunofluorescence assay. As a result, we observed that serum deprivation in H9c2 cells increased PTEN expression. Functionally, the PTEN knockdown experiment using siRNA inhibited serum deprivation-induced cell apoptosis, ROS production, and DNA damage, whereas increased cell proliferation. All these effects could be reversed by phosphatidylinositol 3-kinase (PI3K) inhibitor, which indicated the PI3K/protein kinase B (AKT) might be the critical component of the PTEN effects during serum deficiency. In conclusion, our study indicated the role of the PTEN/PI3K/AKT pathway in serum deprivation-induced cytotoxicity in H9c2 cells.

Background New-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on subsequent heart failure (HF) is still not well studied. We aimed to investigate the relationship between NOAF following AMI and HF hospitalization. Methods This retrospective cohort study was conducted between February 2014 and March 2018, using data from the New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai registry, where all participants did not have a documented AF history. Patients with AMI who discharged alive and had complete echocardiography and follow-up data were analyzed. The primary outcome was HF hospitalization, which was defined as a minimum of an overnight hospital stay of a participant who presented with symptoms and signs of HF or received intravenous diuretics. Results A total of 2075 patients were included, of whom 228 developed NOAF during the index AMI hospitalization. During up to 5 years of follow-up (median: 2.7 years), 205 patients (9.9%) experienced HF hospitalization and 220 patients (10.6%) died. The incidence rate of HF hospitalization among patients with NOAF was 18.4% per year compared with 2.8% per year for those with sinus rhythm. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (hazard ratio [HR]: 3.14, 95% confidence interval [CI]: 2.30–4.28; p Conclusion NOAF complicating AMI is strongly associated with an increased long-term risk of heart. Cumulative incidence of outcome Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. National Natural Science Foundation of China, 2. Natural Science Foundation of Shanghai

Background The prognostic implication of the burden of paroxysmal new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to determine the impact of NOAF burden on long-term cardiovascular outcomes in the setting of AMI. Methods This retrospective study was conducted to investigate the association of NOAF burden with the major adverse cardiac events (MACE, a composite of cardiovascular death, recurrent MI, worsening of heart failure, or ischemic stroke), using data from the New Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai registry. AF burden was defined as the percentage of time (%) spent in AF. Patients with paroxysmal NOAF were divided into three groups according to AF burden tertiles: low burden: 22.4%. A restricted cubic spline analysis was performed to illusrate the relationship between the burden of NOAF and MACE. Results Of 2399 participants, 278 developed NOAF during a median monitoring period of 194.9 hours. The mean age was 65.8±12.4 years, and the median burden of NOAF was 8.4% (IQR: 1.9%-38.1%). During up to 5-years follow-up, the incidence of MACE was 8.6, 17.4, 35.4, and 79.2 per 100 person-years in the sinus rhythm, low-, intermediate-, and high-burden groups, respectively. After adjustment, patients with high NOAF burden had the highest risk of MACE (hazard ratio [HR]: 3.10; 95% confidence interval [CI]: 2.36–4.07), cardiovascular death (HR: 2.26; 95% CI: 1.58–2.23), worsening of heart failure (HR: 4.90; 95% CI: 3.48–4.91), and ischemic stroke (HR: 4.42; 95% CI: 2.03–9.63). Our splines analyses uncovered a nonlinear dose-response pattern, as the HRs of MACEs increased with the progression of NOAF burden and appeared stable after approximately 15% of NOAF burden. Conclusions A greater burden of NOAF during AMI was strongly associated with a higher risk of adverse cardiovascular events. Cumulative incidence of outcomes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. National Natural Science Foundation of China, 2. Natural Science Foundation of Shanghai

The aim of the study was to investigate the correlation between levels of 25-hydroxyvitamin D3, vitamin B12 and C and endothelial function of patients with coronary heart disease (CHD). Forty patients with CHD diagnosed in Shanghai Tenth People's Hospital from May 2016 to April 2017 were selected as the observation group. A total of 45 healthy individuals were selected as the control group. The participants included 54 males and 31 females. General information was collected. Peripheral serum biochemical indicators, levels of 25-hydroxyvitamin D3, vitamin B12 and C, homocysteine (Hcy), nitric oxide (NO) and endothelial NOS (eNOS) were measured. Arterial lesions detected by coronary angiography were recorded and indexes of observation and control group were compared for the correlation analysis. A proportion of hypertensive patients and their body mass index (BMI) were significantly higher in the observation than in the control group (P