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Background METTL3 is the core catalytic enzyme in m6A and is involved in a variety of cardiovascular diseases. However, whether and how METTL3 plays a role during angiotensin II (Ang-II)-induced myocardial hypertrophy is still unknown. Methods Neonatal rat cardiomyocytes (NRCMs) and C57BL/6J mice were treated with Ang-II to induce myocardial hypertrophy. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. Gene function was verified by knockdown and/or overexpression, respectively. Luciferase and RNA immunoprecipitation (RIP) assays were used to verify interactions among multiple genes. Wheat germ agglutinin (WGA), hematoxylin and eosin (H&E), and immunofluorescence were used to examine myocardial size. m6A methylation was detected by a colorimetric kit. Results METTL3 and miR-221/222 expression and m6A levels were significantly increased in response to Ang-II stimulation. Knockdown of METTL3 or miR-221/222 could completely abolish the ability of NRCMs to undergo hypertrophy. The expression of miR-221/222 was positively regulated by METTL3, and the levels of pri-miR-221/222 that bind to DGCR8 or form m6A methylation were promoted by METTL3 in NRCMs. The effect of METTL3 knockdown on hypertrophy was antagonized by miR-221/222 overexpression. Mechanically, Wnt/β-catenin signaling was activated during hypertrophy and restrained by METTL3 or miR-221/222 inhibition. The Wnt/β-catenin antagonist DKK2 was directly targeted by miR-221/222, and the effect of miR-221/222 inhibitor on Wnt/β-catenin was abolished after inhibition of DKK2. Finally, AAV9-mediated cardiac METTL3 knockdown was able to attenuate Ang-II-induced cardiac hypertrophy in mouse model. Conclusions Our findings suggest that METTL3 positively modulates the pri-miR221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/β-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy. AAV9-mediated cardiac METTL3 knockdown could be a therapeutic for pathological myocardial hypertrophy.

Myanmar is globally significant for biodiversity conservation but is facing unique challenges as a result of the current political situation, which has led to unsustainable use of natural resources, withdrawal of conservation funds and a governance vacuum that hinders effective conservation. Given these challenges, there is a need to empower local civil society to implement community-led conservation programmes. We report on locally-led surveys of the Critically Endangered white-bellied heron Ardea insignis in northern Myanmar. We recorded the species’ occurrence along rivers and streams across two river catchments in Kachin state during June 2022–December 2023. We sighted white-bellied herons on 25 occasions and we estimate the local population to be 3–5 individuals. Opportunistic hunting using home-made air-pressured guns is a major threat to wildlife in the region and we documented two white-bellied herons shot in the area since 2019. Threats are exacerbated by a lack of wildlife law enforcement as a result of the country’s political unrest. We describe our initial efforts to implement a community-led approach to foster local stewardship in species and habitat management.

Objective: To explore the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the short-term prognosis of NSTEMI and STEMI. Methods: This study was a single-center, retrospective and observational study. 2618 patients including 1289 NSTMI and 1329 STEMI patients were enrolled from June 2013 to February 2018 in Zhongda Hospital, Southeast University. The demographic information, clinical characteristics, medical history, laboratory examination, treatment, and outcome of individuals at admission and during hospitalization were extracted from the electronic medical record system. Outcome was defined as the all-cause death during hospitalization. Results: (1) In the NSTEMI group, the ability of NLR in predicting in-hospital death (AUC = 0.746) was higher than the neutrophil-monocyte ratio (NMR) (AUC = 0.654), the platelet-lymphocyte ratio (PLR) (AUC = 0.603) and the lymphocyte-monocyte ratio (LMR) (AUC = 0.685), and also higher than AST (AUC = 0.621), CK (AUC = 0.595), LDH (AUC = 0.653) and TnI (AUC = 0.594). The AUC of NLR in the STEMI group was only 0.621. (2) The optimal cut-off value of NLR in NSTEMI group was 5.509 (Youden index = 0.447, sensitivity = 77.01%, specificity = 67.72%). After adjusting variables including age, sex, diabetes history, smoking history, LDL-C and Cr, the logistic regression showed that the patients with NLR>5.509 had higher hazard risk of death (HR4.356; 95%CI 2.552–7.435; P < 0.001) than the patients with NLR ≤ 5.509. (3) Stratification analysis showed that the in-hospital mortality of patients with NLR > 5.509 was 14.611-fold higher than those with NLR ≤ 5.509 in patients aged <76, much higher than the ratio in patients aged ≥ 76. For patients with creatinine levels ≤ 71, the in-hospital death risk in high NLR group was 10.065-fold higher than in low NLR group (95%CI 1.761–57.514, P = 0.009), while the HR was only 4.117 in patients with creatinine levels > 71. The HR in patients with or without diabetes were 6.586 and 3.375, respectively. The HR in smoking or no smoking patients were 6.646 and 4.145, respectively. The HR in patients with LDL-C ≥ 2.06 or <2.06 were 5.526 and 2.967 respectively. Conclusion: Compared to NMR, PLR, and LMR, NLR had the best ability in predicting in-hospital death after NSTEMI. Age, creatinine, LDL-C, diabetes and smoking history were all important factors affecting the predictive efficiency in NSTEMI. NLR had the limited predictive ability in STEMI.

Specific protein 1 (SP1) might act as a critical transcription regulator in myocardial infarction (MI), but little evidence abóut its function in regulating cardiac apoptosis, a major cause of MI development, has been revealed. This study tried to investigate the role of SP1 in MI and its interaction with poly-ADP-ribose polymerase (PARP)-1 by using SP1 inhibitor, mithramycin A (mithA). Primary mouse cardiomyocytes and commercial mouse cardiomyocytes were subjected to mithA treatment under hypoxia conditions, while cell viability, Nix promoter activity, and its expression were detected correspondingly. PARP overexpression and knockdown were conducted, respectively, in mithA-treated and SP1-overexpressing cells. Coimmunoprecipitation was used to verify the interaction between PARP and SP1. For in vivo experiments, mithA administration was performed after the injections of adenovirus for PARP overexpression, and then, MI introduction was carried out. Infarct size and lactate dehydrogenase level were measured to assess MI injury. SP1 inhibitor mithA attenuated hypoxia-induced decrease of cell viability and Nix transcriptional activation, which could be inhibited by PARP overexpression. Knockdown of PARP prevented SP1 -induced transcription of Nix and cell viability change, and PARP showed direct interaction with SP1. Furthermore, mithA administration reduced MI injuries, while PARP overexpression could suppress the improvement. The cardioprotective role of SP1 inhibitor mithA was demonstrated here expanding the role of SP1 in MI development involving hypoxia-induced cardiac apoptosis. Moreover, PARP acted as a transcriptional coactivator in Nix transcription involving its interaction with SP1.

Acute myocardial infarction (AMI) is one of the fatal cardiac emergencies. The detection of triggering receptor expressed on myeloid cells 1 (TREM1), a cell surface immunoglobulin that amplifies pro-inflammatory responses, screened by bioinformatics was shown to be significant in diagnosing and predicting the prognosis of AMI. GSE66360, GSE61144 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between AMI and control groups using R software. A total of 147 patients in total were prospectively enrolled from October 2018 to June 2019 and divided into two groups, the normal group ( = 35) and the AMI group ( = 112). Plasma was collected from each patient at admission and all patients received 6-month follow-up care. According to bioinformatic analysis, TREM1 was an important DEG in patients with AMI. Compared with the normal group, TREM1 expression was markedly increased in the AMI group ( < 0.001). TREM1 expression was positively correlated with fasting plasma glucose (FPG), glycosylated hemoglobin (HbAC), and the number of lesion vessels, although it had no correlation with Gensini score. TREM1 expression in the triple-vessels group was significantly higher than that of the single-vessel group ( < 0.05). Multiple linear regression showed that UA and HbAC were two factors influencing TREM1 expression. The ROC curve showed that TREM1 had a diagnostic significance in AMI ( < 0.001), especially in AMI patients without diabetes. Cox regression showed increased TREM1 expression was closely associated with 6-month major adverse cardiac events (MACEs) ( < 0.001). TREM1 is a potentially significant biomarker for the diagnosis of AMI and may be closely associated with the severity of coronary lesions and diabetes. TREM1 may also be helpful in predicting the 6-month MACEs after AMI.

Background: This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome. Methods: Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups. Results: This post-hoc analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) ( p = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area ( p = 0.017, 0.040, and <0.001, respectively). Thrombus was more prevalent in QFR-T1 (39%) than in QFR-T2 (3%), and QFR-T3 (12%) ( p = 0.001 and 0.020, respectively). In the multivariable analysis, QFR ≤ 0.80 remained as a significant determinant of OCT-TCFA regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted OR: 4.387, 95% CI 1.297–14.839, p = 0.017). The diagnostic accuracy of QFR was moderate in identifying lesions with OCT-TCFA (area under the curve: 0.72, 95% CI 0.58–0.86, p = 0.003). In the IVUS cohort, significant differences were found between two groups in minimal lumen area and plaque burden but not in the distribution of virtual histology (VH)-TCFA ( p = 0.025, 0.036, and 1.000, respectively). Conclusions: Lower QFR was related to OCT-defined plaque vulnerability in angiographically mild-to-intermediate lesions. The QFR might be a useful tool for ruling out high-risk plaques without using any pressure wire or vasodilator.

The etiology of dilated cardiomyopathy (DCM) is unclear. Bioinformatics algorithms may help to explore the underlying mechanisms. Therefore, we aimed to screen diagnostic biomarkers and identify the landscape of immune infiltration in DCM. First, the CIBERSORT algorithm was used to excavate the proportion of immune-infiltration cells in DCM and normal myocardial tissues. Meanwhile, the Pearson analysis and principal component analysis (PCA) were used to identify immune heterogeneity in different tissues. The Wilcoxon test, LASSO regression, and machine learning method were conducted to identify the hub immune cells. In addition, the differentially expressed genes (DEGs) were screened by the limma package, and DEGs were analyzed for functional enrichment. In the protein-protein interaction (PPI) network, multiple algorithms were used to calculate the score of each DEG for screening the hub genes. Subsequently, external datasets were used to further validate the expression of hub genes, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Finally, we examined the expression of hub biomarkers in animal models. A total of 108 DEGs were screened, and these genes may be related to biological processes such as cytolysis, positive regulation of cytokine secretion, etc. Two types of hub immune cells [activated natural killer (NK) cells and eosinophils] and four hub genes ( , and ) were identified in DCM myocardial tissues. was verified to have the capability to diagnose DCM with the most excellent specificity and sensitivity. It is worth mentioning that the combined and eosinophils may have better diagnostic efficacy. Moreover, the correlation analysis showed was negatively correlated with activated NK cells. Finally, the results of the mice model also indicated that might be involved in the occurrence of DCM. , and may have a potential predictive ability for DCM, and especially showed the most robust efficacy. Furthermore, activated NK cells and eosinophils may relate to the occurrence of DCM.

Aging is associated with impaired vascular repair following ischemic insult, largely due to reparative dysfunctions of progenitor cells. Activation of Mas receptor (MasR) was shown to reverse aging-associated vasoreparative dysfunction. This study tested the impact of MasR-deficiency on mobilization and vasoreparative functions with aging. Wild type (WT) or MasR-deficient mice (MasR −/− or MasR +/− ) at 12–14 weeks (young) or middle age (11–12 months) (MA) were used in the study. Mobilization of lineage-negative, Sca-1-positive cKit-positive (LSK) cells in response to G-CSF or plerixafor was determined. Hindlimb ischemia (HLI) was induced by femoral artery ligation. Mobilization and blood flow recovery were monitored post-HLI. Radiation chimeras were made by lethal irradiation of WT or MasR −/− mice followed by administration of bone marrow cells from MasR −/− or WT mice, respectively. Nitric oxide (NO) generation by stromal-derived factor-1α (SDF) and mitochondrial reactive oxygen species (mitoROS) levels were determined by flow cytometry. Effect of A779 treatment on mobilization, blood flow recovery, and NO and ROS levels were determined in young WT and MasR +/− mice. Circulating LSK cells in basal or in response to plerixafor or G-CSF or in response to ischemic injury were lower in MasR −/− mice compared to the WT. Responses in MasR +/− mice were similar to the WT at young age but at the middle age, impairments were observed. Impaired mobilization to ischemia or G-CSF was rescued in WT → MasR −/− chimeras. NO levels were lower and mitoROS were higher in MasR −/− LSK cells compared to WT cells. A779 precipitated dysfunctions in young-MasR +/− mice similar to that observed in MA-MasR +/− , and this accompanied decreased NO generation by SDF and enhanced mitoROS levels. This study shows that mice at MA do not exhibit vasoreparative dysfunction. Either partial or total loss of MasR precipitates advanced-aging phenotype likely due to lack of NO and oxidative stress.

Acute myocardial infarction (AMI) represents the acute manifestation of coronary artery disease. In recent years, microRNAs (miRNAs) have been extensively studied in AMI. This study focused on the role of miR-431-5p in AMI and its effect on cardiomyocyte apoptosis after AMI. The expression of miR-431-5p was analyzed by quantitative real-time PCR (qRT-PCR). By interfering with miR-431-5p in hypoxia-reoxygenation (H/R)-induced HL-1 cardiomyocytes, the effect of miR-431-5p on cardiomyocyte apoptosis after AMI was examined. The interaction between miR-431-5p and selenoprotein T (SELT) mRNA was verified by dual-luciferase reporter assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. Cell viability was examined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The results of qRT-PCR showed that the expression of miR-431-5p in AMI myocardial tissues and H/R-induced HL-1 cardiomyocytes was significantly increased. After interfering with miR-431-5p, the expression of SELT in HL-1 cells was up-regulated, cell apoptosis was decreased, cell viability was increased, and lactate dehydrogenase (LDH) activity was decreased. The dual-luciferase reporter assay confirmed the targeting relationship between miR-431-5p and SELT1 3’ untranslated region (UTR). In H/R-induced HL-1 cells, the simultaneous silencing of SELT and miR-431-5p resulted in a decrease of Bcl-2 expression, an increase of Bax expression, and an increase of cleaved-caspase 3 expression compared with silencing miR-431-5p alone. Also, cell viability was decreased, while LDH activity was increased by the simultaneous silencing of SELT and miR-431-5p. Interfering miR-431-5p protected cardiomyocytes from AMI injury via restoring the expression of SELT, providing new ideas for the treatment of AMI.

Three different LED spectra (W: White light; WFR: W + far-red light; WB: W + blue light) with similar photosynthetic photon flux density (PPFD) were designed to explore the effects of supplementary far-red and blue lights on leaf color, biomass and phytochemicals of two cultivars of red-leaf lettuce (“Yanzhi” and “Red Butter”) in an artificial lighting plant factory. Lettuce plants under WB had redder leaf color and significantly higher contents of pigments, such as chlorophyll a, chlorophyll b, chlorophyll (a + b) and anthocyanins. The accumulation of health-promoting compounds, such as vitamin C, vitamin A, total phenolic compounds, total flavonoids and anthocyanins in the two lettuce cultivars were obviously enhanced by WB. Lettuce under WFR showed remarkable increase in fresh weight and dry weight; meanwhile, significant decreases of pigments, total phenolic compounds, total flavonoids and vitamin C were found. Thus, in the plant factory system, the application of WB can improve the coloration and quality of red leaf lettuce while WFR was encouraged for the purpose of elevating the yield of lettuce.