The rice LATE ELONGATED HYPOCOTYL enhances salt tolerance by regulating Na+/K+ homeostasis and ABA signalling.

The circadian clock plays multiple functions in the regulation of plant growth, development and response to various abiotic stress. Here, we showed that the core oscillator component late elongated hypocotyl (LHY) was involved in rice response to salt stress. The mutations of OsLHY gene led to reduced salt tolerance in rice. Transcriptomic analyses revealed that the OsLHY gene regulates the expression of genes related to ion homeostasis and the abscisic acid (ABA) signalling pathway, including genes encoded High-affinity K+ transporters (OsHKTs) and the stress-activated protein kinases (OsSAPKs). We demonstrated that OsLHY directly binds the promoters of OsHKT1;1, OsHKT1;4 and OsSAPK9 to regulate their expression. Moreover, the ossapk9 mutants exhibited salt tolerance under salt stress. Taken together, our findings revealed that OsLHY integrates ion homeostasis and the ABA pathway to regulate salt tolerance in rice, providing insights into our understanding of how the circadian clock controls rice response to salt stress.

A new demethylase gene, OsDML4, is involved in high temperature-increased grain chalkiness in rice.

High temperature (HT) can affect the accumulation of seed storage materials and cause adverse effects on the yield and quality of rice. DNA methylation plays an important role in plant growth and development. Here, we identified a new demethylase gene OsDML4 and discovered its function in cytosine demethylation to affect endosperm formation. Loss of function of OsDML4 induced chalky endosperm only under HT and dramatically reduced the transcription and accumulation of glutelins and 16 kDa prolamin. The expression of two transcription factor genes RISBZ1 and RPBF was significantly decreased in the osdml4 mutants, which caused adverse effects on the formation of protein bodies (PBs) with greatly decreased PB-II number, and incomplete and abnormally shaped PB-IIs. Whole-genome bisulfite sequencing analysis of seeds at 15 d after pollination revealed much higher global methylation levels of CG, CHG, and CHH contexts in the osdml4 mutants compared with the wild type. Moreover, the RISBZ1 promoter was hypermethylated but the RPBF promoter was almost unchanged under HT. No significant difference was detected between the wild type and osdml4 mutants under normal temperature. Our study demonstrated a novel OsDML4-mediated DNA methylation involved in the formation of chalky endosperm only under HT and provided a new perspective in regulating endosperm development and the accumulation of seed storage proteins in rice.

Visit-to-visit fasting plasma glucose variability is associated with left ventricular adverse remodeling in diabetic patients with STEMI.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to poor cardiovascular outcomes after ST-segment elevation myocardial infarction (STEMI). Left ventricular adverse remodeling (LVAR) triggered upon myocardial infarction is recognized as the predominant pathological process in the development of heart failure. In the present study, we sought to investigate whether visit-to-visit fasting plasma glucose (FPG) variability is a potential predictor of LVAR in T2DM patients after STEMI. METHODS: From January 2014 to December 2018 in Ruijin Hospital, T2DM patients with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for ~ 12 months. The changes in left ventricular geometric and functional parameters between baseline and 12-month follow-up were assessed by echocardiography. The incidence of LVAR, defined as 20% increase in indexed left ventricular end-diastolic volume (LVEDV), and its relationship with visit-to-visit FPG variability were analyzed. Multivariate regression models were constructed to test the predictive value of FPG variability for post-infarction LVAR. RESULTS: A total of 437 patients with type 2 diabetes and STEMI were included in the final analysis. During a mean follow-up of 12.4 ± 1.1 months, the incidence of LVAR was 20.6% and mean enlargement of indexed LVEDV was 3.31 ± 14.4 mL/m2, which was significantly increased in patients with higher coefficient variance (CV) of FPG (P = 0.002) irrespective of baseline glycemic levels. In multivariate analysis, FPG variability was independently associated with incidence of post-infarction LVAR after adjustment for traditional risk factors, baseline HbA1c as well as mean FPG during follow-up (OR: 3.021 [95% CI 1.081-8.764] for highest vs. lowest tertile of CV of FPG). Assessing FPG variability by other two measures, including standard deviation (SD) and variability independent of the mean (VIM), yielded similar findings. CONCLUSIONS: This study suggests that visit-to-visit FPG variability is an independent predictor of incidence of LVAR in T2DM patients with STEMI. Trial registration Trials number, NCT02089360; registered on March 17,2014.

Impact of coronary collateralization on long-term clinical outcomes in type 2 diabetic patients after successful recanalization of chronic total occlusion.

BACKGROUND: To assess the prognostic role of coronary collaterals in patients with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: Coronary collateralization was graded according to Rentrop scoring system in 198 type 2 diabetic patients and 335 non-diabetics with stable angina undergoing PCI for at least one CTO lesion. Left ventricular ejection fraction (LVEF) was determined and major adverse cardio-cerebral events (MACCE) were recorded during follow-up. RESULTS: Poor collateralization was more common in patients with T2DM than in non-diabetics (40% vs 29%, p = 0.008). At 13.5 ± 4.1 months, the rate of composite MACCE (17.3% vs 27.6%, p = 0.034) and repeat revascularization (15.2% vs 25.5%, p = 0.026) was lower and the increase in LVEF (3.10% vs 1.80%, p = 0.024) was greater in patients with good collaterals than in those with poor collaterals for non-diabetic group. The associations were in the same direction for T2DM group (35% vs 44%; 30% vs 36%; 2.14% vs 1.65%, respectively) with a higher all-cause mortality in diabetic patients with poor collaterals (p = 0.034). Multivariable Cox proportional hazards analysis showed that coronary collateralization was an independent factor for time to MACCE (HR 2.155,95% CI 1.290-3.599, p = 0.003) and repeat revascularization (HR 2.326, 95% CI 1.357-3.986, p = 0.002) in non-diabetic patients, but did not enter the model in those with T2DM. CONCLUSIONS: T2DM is associated with reduced coronary collateralization. The effects of the status of coronary collateralization on long-term clinical outcomes and left ventricular function appear to be similar in size in type 2 diabetic patients and non-diabetics after successful recanalization of CTO.

Visit-to-visit HbA1c variability is associated with in-stent restenosis in patients with type 2 diabetes after percutaneous coronary intervention.

BACKGROUND: Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation. METHODS: We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR. RESULTS: From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P < 0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14-7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings. CONCLUSIONS: This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation. Trial registration NCT02089360: NCT.

Insulin resistance and dysglycemia are associated with left ventricular remodeling after myocardial infarction in non-diabetic patients.

BACKGROUND: Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients. METHODS: A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied. RESULTS: Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001). CONCLUSIONS: Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation. Trial registration Trials number, NCT02089360; registered on March 17, 2014.

Lipoprotein (a) interactions with cholesterol-containing lipids on angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion.

BACKGROUND: We investigated whether or to what extent the interaction of lipoprotein (a) [Lp(a)] with cholesterol-containing lipids was associated with angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion. METHODS: Serum levels of Lp(a), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride were determined and non-HDL-C was calculated in 706 type 2 diabetic and 578 non-diabetic patients with stable coronary artery disease and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3). RESULTS: For diabetic and non-diabetic patients, Lp(a), total cholesterol, LDL-C, and non-HDL-C levels were higher in patients with poor coronary collateralization than in those with good collateralization, whereas HDL-C and triglyceride levels were similar. After adjustment for potential confounding factors, tertiles of Lp(a), total cholesterol, LDL-C and non-HDL-C remained independent determinants for poor collateralization. A significant interaction between Lp(a) and total cholesterol, LDL-C or non-HDL-C was observed in diabetic patients (all P interaction < 0.001) but not in non-diabetics. At high tertile of total cholesterol (≥ 5.35 mmol/L), LDL-C (≥ 3.36 mmol/L) and non-HDL-C (≥ 4.38 mmol/L), diabetic patients with high tertile of Lp(a) (≥ 30.23 mg/dL) had an increased risk of poor collateralization compared with those with low tertile of Lp(a) (< 12.66 mg/dL) (adjusted OR = 4.300, 3.970 and 4.386, respectively, all P < 0.001). CONCLUSIONS: Increased Lp(a) confers greater risk for poor coronary collateralization when total cholesterol, LDL-C or non-HDL-C are elevated especially for patients with type 2 diabetes.

Donor artery stenosis interactions with diastolic blood pressure on coronary collateral flow in type 2 diabetic patients with chronic total occlusion.

BACKGROUND: We investigated whether and to what extent stenosis of predominant collateral donor artery (PCDA) affects coronary collateral flow in relation to blood pressure (BP) in type 2 diabetic patients with chronic total occlusion (CTO). METHODS: Collateral flow index (CFI) as derived from intracoronary pressure distal to occluded segment and mean aortic pressure in 220 type 2 diabetic patients and 220 propensity score matched non-diabetic controls undergoing percutaneous coronary intervention for CTO. The severity of PCDA stenosis was graded according to lumen diameter narrowing. RESULTS: CFI decreased stepwise from mild to severe stenosis of the PCDA and was lower in diabetic patients with moderate or severe PCDA stenosis than in non-diabetic controls (0.36 ± 0.10 vs. 0.45 ± 0.08, P < 0.001; 0.29 ± 0.09 vs. 0.35 ± 0.08, P = 0.008). When the PCDA was mildly stenotic, CFI increased initially along with a reduction in diastolic BP, and decreased when diastolic BP was below 60 mmHg in diabetic patients (0.38 ± 0.16 vs. 0.57 ± 0.09, P < 0.001). In the presence of moderate PCDA stenosis, diabetic patients had significantly lower CFI compared to non-diabetic controls, with a relative reduction of 19.8% at diastolic BP 70-79 mmHg, 28.2% at 60-69 mmHg and 38.2% below 60 mmHg (all P < 0.05). A severe PCDA stenosis resulted in a more pronounced decrease in CFI, with a relative reduction of 37.3% for diabetics compared to non-diabetics when diastolic BP was below 60 mmHg (P = 0.050). CONCLUSIONS: In the setting of CTO, donor artery stenosis confers greater risk for reduced coronary collateral flow when diastolic BP is decreased. Even a moderate stenosis in the PCDA may be associated with lower collateral flow as diastolic BP decreases below 80 mmHg in type 2 diabetic than in non-diabetic patients.

Increased glycated albumin and decreased esRAGE levels in serum are related to negative coronary artery remodeling in patients with type 2 diabetes: an Intravascular ultrasound study.

BACKGROUND: Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients. METHODS: Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI < 0.95 and intermediate or positive remodeling as an RI ≥ 0.95. RESULTS: Mean plaque burden at the lesion site was 70.96 ± 9.98%, and RI was 0.96 ± 0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r = 0.236, P = 0.005) and was inversely related to serum GA level (r = - 0.240, P = 0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r = - 0.206, P = 0.014) and total cholesterol levels (r = - 0.183, P = 0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012-0.564, P = 0.021), GA (OR 1.093; 95% CI 1.013-1.179, P = 0.018) and LDL-C (OR 1.479; 95% CI 1.072-2.835, P = 0.023) as independent predictors for negative remodeling. CONCLUSIONS: In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.

Correlates and outcomes related to periprocedural myocardial injury during percutaneous coronary intervention for chronic total occlusion: Results from a prospective, single center PCI registry.

BACKGROUND: There is increasing interest in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Periprocedural myocardial injury (PMI) post CTO PCI is not uncommon, but true incidence and implications of PMI are not well understood. OBJECTIVES: This study aimed to investigate risk factors for PMI post CTO PCI and its implications for the 1-year clinical outcome of a Chinese population. METHODS: Baseline characteristics, procedure features, and major adverse cardiac events (MACE) at 1 year were assessed in 629 consecutive patients who underwent CTO PCI. PMI was diagnosed as an elevation of creatine kinase MB ≥3 times ULN 12-24 hr post procedure. Multivariate analysis was performed to determine the correlates of PMI and MACE at 1-year follow-up. RESULTS: In total, PMI was detected in 115 patients (18.3%). Compared with patients without PMI, those with PMI had a higher percentage of previous coronary artery bypass grafting (CABG), right coronary occlusion and side branch occlusion, and technical success was lower in the PMI group (90.4% vs. 96.7%, P = 0.003). One-year MACE-free survival was reduced in the PMI group (87.8% vs. 95.9%, P = 0.001). The final TIMI flow 0-1 (OR 2.23, 95%CI 1.06-4.87, P = 0.02), side branch occlusion (OR 2.67, 95%CI 1.19-7.11, P = 0.009), retrograde PCI (OR 1.35, 95%CI 1.10-2.74, P = 0.04), and history of prior CABG (OR 2.41, 95%CI 1.38-5.91, P = 0.01) were independent risk factors for the occurrence of PMI. CONCLUSIONS: In this unique Chinese cohort, PMI post CTO PCI was associated with several clinical and angiographic factors and exerts an adverse effect on 1-year clinical outcomes.

Periprocedural use of tirofiban in elective percutaneous coronary intervention for long coronary lesions in stable patients with overlapping drug-eluting stents--the PETITION study: a prospective, randomized, multicenter study.

BACKGROUND AND PURPOSE: Patients are at risk of developing periprocedural myonecrosis after percutaneous coronary intervention (PCI). We investigated whether the use of the platelet glycoprotein (GP) IIb/IIIa receptor inhibitor tirofiban could reduce periprocedural myocardial infarction (PMI) in patients with stable coronary artery disease undergoing elective PCI with overlapping stent implantation for long lesions. METHODS: A total of 748 stable angina patients with long lesions (≥ 40 mm in length) treated with overlapping stent implantation were randomly assigned to receive tirofiban (tirofiban group; n = 373) or conventional therapy (control group; n = 375). Intravenous tirofiban was initiated before PCI and maintained for 12 hr after the procedure. The primary endpoint was PMI, defined as an elevation in CK-MB > 3 times the upper limit of normal 12 hr after the index procedure. The secondary endpoint was major adverse cardiac events (MACE), including cardiac death, target vessel revascularization, and recurrent MI (re-MI), at one-year of clinical follow-up. The safety end-points included Thrombolysis in Myocardial Infarction (TIMI) major bleeding and stent thrombosis. RESULTS: Despite comparable angiographic and procedural characteristics, in the intention-to-treatment analysis, the primary endpoint was significantly reduced in the tirofiban group (4.0% vs. 11.5%, P < 0.001). Multivariate analysis revealed that the adjunctive use of tirofiban was the only negative predictor of PMI (OR 0.41, 95% CI 0.28-0.81, P < 0.01). At one-year of clinical follow-up, the overall occurrence of MACE was significantly lower in the tirofiban group (13.4% vs. 22.7%, P = 0.001). The rate of TIMI major bleeding and stent thrombosis did not differ significantly between the two groups. CONCLUSION: Our results show that the adjunctive use of tirofiban reduces the occurrence of PMI and MACE at one year in stable coronary artery disease patients undergoing elective PCI for long lesions with overlapping stent implantation.

Comparison of biodegradable polymer versus durable polymer sirolimus-eluting stenting in patients with acute st-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the RESOLVE study.

BACKGROUND: Sirolimus-eluting stents (SES) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients. We compared the efficacy of these 2 stent types in patients with acute myocardial infarction (STEMI). METHODS: One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable (n = 596) or durable polymer (n = 596). The study end-point was the composite of major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction (MI), or target lesion revascularization (TLR) at 1-year follow-up. Secondary end-points included individual components of primary end-point and stent thrombosis. RESULTS: Compared with durable polymer SES, the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9% in the primary end-point (12.4% vs. 13.3%, P = 0.67) and an upper limit of one-sided 95% confidence interval (CI) of 2.96% (P for noninferiority = 0.001). Rate of death, recurrent MI, and TLR were 7.9% and 8.6% (HR: 0.92; 95% CI: 0.61-1.38, P = 0.67), 2.9% and 3.5% (HR: 0.80; 95% CI: 0.42-1.54, P = 0.51), and 2.0% and 3.2% (HR: 0.62; 95% CI: 0.30-1.30, P = 0.20) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up, respectively. Despite similar rates of 30-day ARC definite/probable stent thrombosis, late stent thrombosis (stent thrombosis occurring beyond 30 days) was lower with biodegradable polymer SES (0.7% vs. 2.2%, P = 0.028). CONCLUSIONS: In patients undergoing primary PCI for STEMI, the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES.

Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum?

Praziquantel is currently the only drug of choice for the treatment of human schistosomiases. However, it has been proved that Schistosoma japonicum subjected to drug pressure may develop resistance to praziquantel. To evaluate the efficacy of dihydroartemisinin against praziquantel-resistant S. japonicum, mice infected with a praziquantel-resistant isolate and a praziquantel-susceptible isolate of S. japonicum were treated with dihydroartemisinin at a single oral dose of 300 mg/kg given once on each of 35-36 post-infection days, while infected but untreated mice served as controls. All mice were sacrificed 50 days post-infection, and the worm burden reductions were estimated. Administration of dihydroartemisinin at a single oral dose of 300 mg/kg on each of 35-36 post-infection days reduced total worm burdens of 69.8% and female worm burdens of 86% in mice infected with the praziquantel-susceptible isolate, and total worm burdens of 66.1% and female worm burdens of 85.1% in mice infected with the praziquantel-resistant isolate (both P values > 0.05). It is concluded that the sensitivity of artemisinin derivative dihydroartemisinin does not reduce in praziquantel-resistant S. japonicum.

A meta-analysis of the intervention effect of mindfulness training on athletes' performance.

Objective: To explore the intervention effect of mindfulness training on athletes' performance using meta-analysis method. Methods: A total of 11 articles and 23 effect sizes were included through retrieval of Chinese and English databases, with a total sample size of 582. Result: Mindfulness training improves the level of mindfulness [SMD =1.08, 95%CI (0.30, 1.86), p < 0.01], fluency (The optimal competitive psychological state of the athlete, the athlete's attention is all focused on the task, and other things no longer attract their attention) [SMD =1.47, 95%CI (0.87, 2.08), p < 0.001] and performance [SMD =0.92, 95% CI (0.40, 1.43), p < 0.01], reduced psychological anxiety [SMD = -0.87, 95% CI (-1.54, -0.20), p < 0.05], and all reached the level of large effect size. Conclusion: The effect of mindfulness training on athletes' sports performance is effective, and it can be used as an effective psychological skill intervention method to improve athletes' sports performance. In the future, we should further expand the sample size, strengthen the comparative study of different sports and intervention modes, and pay attention to the difference between the time effect and trait mindfulness level in fluency state.

Ethanol extract of Evodia lepta Merr. ameliorates cognitive impairment through inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.

In vivo activity of dihydroartemisinin against Schistosoma mansoni schistosomula in mice.

Dihydroartemisinin, an anti-malarial agent, has been shown to exhibit activity against Schistosoma japonicum and S. mansoni. The purpose of the present study was to investigate the in vivo activity of dihydroartemisinin against juvenile S. mansoni and the changes to the genital system among worms surviving drug treatment. Mice were infected with 200 S. mansoni cercariae each and randomly assigned to groups. Dihydroartemisinin at a single oral dose of 300 mg/kg was given to mice on Days 14 or 16, 18, 20, 21, 22, 24, 26 or 28 post-infection, to assess the efficacy of dihydroartemisinin against juvenile S. mansoni. Mice were treated with dihydroartemisinin using various protocols with the total drug dose of 900 mg/kg, to investigate the efficacy of dihydroartemisinin against the schistosomula of S. mansoni. In addition, changes to the genital system among worms surviving dihydroartemisinin treatment, were recorded. An oral dose of dihydroartemisinin of 300 mg/kg was given to mice on Days 14, 16, 18, 20, 21, 22, 24, 26 or 28 days post-infection; this resulted in a 65.0-82.4% reduction in total worm burden and a 70.9-83.0% female worm burden. Better results were seen when treatment was given 20-24 days post-infection. Administration of multiple-dose and low-oral-dose dihydroarteminisinin (at doses of 90, 180, 300 and 450 mg/kg) at different times, reduced total worm burdens by 88.7-99.1% and female worm burdens by 93.2-99.5%. The egg tubercles in mice livers were significantly reduced following treatment; in some mice no egg tubercles were found. These findings indicate dihydroartemisinin exhibits high in vivo activity against the schistosomula of S. mansoni. It causes damage to the genital system of worms, influences the development of of S. mansoni worms, reduces the oviposition of surviving worms and enhances the formation of granulomas around tissue-trapped eggs, thereby reducing damage to the infected mammalian host.

Loss-of-function mutations of OsbHLH044 transcription factor lead to salinity sensitivity and a greater chalkiness in rice (Oryza sativa L.).

The most hazardous abiotic stress, salinity, restricted the world crop production, and grain chalkiness affected the grain quality to limit consumers' acceptance. The basic helix-loop-helix (bHLH) proteins modulate massive biological processes in plants. Here the CRISPR/Cas9 gene editing mutants were obtained to detect the function of OsbHLH044. The loss-of-function of OsbHLH044 mutants showed numerous altered plant phenotypes. Notably, the osbhlh044 mutants resulted in prominently reduced morphological and physiological parameters under salt stress. Lower antioxidant activities and higher lipid peroxidation and hydrogen peroxide (H2O2) accumulation in the osbhlh044 mutants caused salinity sensitivity due to elevated reactive oxygen species (ROS). Under salt stress, both shoots and roots of the osbhlh044 mutants acquired higher Na+. Moreover, the expression of ion homeostasis-related genes (OsHKTs, OsHAK, OsSOSs, and OsNHX) and ABA-responsive gene (OsLEA3) was significantly altered in the osbhlh044 mutants after salt stress. The expression levels of genes coding for starch (OsAGPL1, OsSSIIa, OsWx, and OsFLO2) and seed storage proteins (GluA1 and Globulin 1) were significantly decreased, indicating that they synthesize less store starch and proteins, resulting in grain chalkiness in the osbhlh044 mutants. Yeast one Hybrid (Y1H) showed that OsbHLH044 could activate salt- (OsHKT1;3, OsHAK7, OsSOS1, OsSOS2, OsNHX2, and OsLEA3 but not OsHKT2;1), and starch-related genes (OsSSIIa, OsWx, and OsFLO2) by binding to the G-boxes of their promoters. Therefore, the OsbHLH044 gene editing mutants revealed multiple functions, specifically a positive regulator of salt stress and grain quality, which might bring new insights into the breeding of rice varieties.

One-year outcome of single-stent crossover versus accurate ostial stenting for isolated left anterior descending ostial stenosis.

BACKGROUND: The optimal strategy of percutaneous coronary intervention (PCI) for isolated left anterior descending (LAD) ostial lesions remains debatable. This study aimed to compare clinical outcomes of patients with isolated LAD ostial stenosis treated by single-stent crossover versus accurate ostial stenting. METHODS: A total of 216 eligible consecutive patients with isolated de novo LAD ostial stenosis were enrolled, and were stratified according to the stenting techniques. Clinical follow-up was performed by review of medical charts or telephone contact with the patients, and repeat angiography was made at 9-12 months after the procedure. Major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, non-fatal stroke and target vessel revascularization (TVR) were recorded. RESULTS: Single-stent crossover and accurate ostial stenting were applied to 78 (36%) and 138 (64%) patients, respectively. During a mean of 13 ± 4.1 months of follow-up, the rate of composite MACE (19.6 vs. 8.9%; P = 0.040) was higher in LAD ostial stenosis patients treated with accurate ostial stenting than those treated with single-stent crossover technique, mainly driven by more frequent TVR (17.4 vs. 7.7%; P = 0.048). PCI strategy was an independent predictor of MACE (hazard ratio 2.561; 95% CI, 1.041-6.299; P = 0.021) in the multivariable Cox regression analysis. CONCLUSIONS: Our retrospective study suggests that the single-stent crossover technique is associated with a better 1-year clinical outcome compared with accurate ostial stenting in patients with isolated LAD ostial stenosis.

OsLHY is involved in regulating flowering through the Hd1- and Ehd1- mediated pathways in rice (Oryza sativa L.).

Flowering time (or heading date in crops) is a critical agronomic trait for rice reproduction and adaptation. The circadian clock is an endogenous oscillator that is involved in controlling photoperiodic flowering. The rice LATE ELONGATED HYPOCOTYL (OsLHY), the core oscillator component of circadian clock, is a homolog of the LHY/CCA1 in Arabidopsis. Here we showed that CRISPR/Cas9-engineered mutations in OsLHY caused late flowering in rice only under natural long-day (nLD) and short-day (nSD) conditions, but not artificial SD (10 h light/14 h dark) conditions. In the oslhy mutant, the diurnal expression of circadian clock-related genes was seriously affected under both LD and SD conditions. Furthermore, the expression of the flowering activators Ehd1, Hd3a and RFT1 was down-regulated and flowering repressors Hd1 and Ghd7 was up-regulated in the oslhy mutant under LD conditions. While the transcripts of flowering-related genes were not dramatically influenced under SD conditions. Dual-luciferase assays showed that OsLHY repressed the transcription of OsGI, Hd1, Ghd7, Hd3a, RFT1 and OsELF3, and activated the transcription of Ehd1. Moreover, the yeast one hybrid assay and electrophoretic mobility shift assay confirmed that OsLHY directly repressed OsGI, RFT1 and OsELF3 by binding to their promoters, which is consistent with that in Arabidopsis. These results suggested that the OsLHY can promote rice flowering mainly through regulating Hd1 and Ehd1.

Circulating Chromogranin B Is Associated With Left Ventricular Functional Recovery After Successful Recanalization of Chronic Total Occlusion.

Background: Chromogranin B (CgB) is increased in heart failure and proportionate to disease severity. We investigated whether circulating CgB level is associated with left ventricular (LV) functional recovery potential after successful recanalization of chronic total occlusion (CTO). Methods: Serum levels of CgB were assayed in 53 patients with stable angina with LV functional recovery [an absolute increase in LV ejection fraction (EF) of ≥5%] and 53 age- and sex-matched non-recovery controls after successful recanalization of CTO during 12-month follow-up. Results: We found that CgB level was significantly lower in the recovery group than in the non-recovery group (593 [IQR 454-934] vs. 1,108 [IQR 696-2020] pg/ml, P < 0.001), and that it was inversely correlated with changes in LVEF (Spearman's r = -0.31, P = 0.001). Receiver operating characteristic (ROC) analysis showed that the area under the curve of CgB for predicting LVEF improvement was 0.76 (95% CI 0.664-0.856), and that the optimal cutoff value was 972.5 pg/ml. In multivariate analyses, after adjusting for confounding factors, high CgB level remained an independent determinant of impaired LV functional recovery after CTO recanalization. LV functional improvement appeared to be more responsive to CgB in patients with poor than with good coronary collaterals. Conclusions: Elevated circulating CgB level confers an increased risk of impaired LV functional recovery after successful recanalization of CTO in patients with stable coronary artery disease.