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Permethrin at 0.4 kg a.i./ha controlled blueberry thrips Frankliniella vaccinii Morgan. There was no plant damage and crop yield was notably increased. Permethrin was extracted from berries with acetone, partitioned in hexane, cleaned‐up on Florisil column and analysed by the electron capture gas chromatography using a 3% OV‐210 column. No permethrin residues were found in the berries. The relative retention times of cis‐, and trans‐permethrins to aldrin were 10.3 and 12.1, respectively. The absence of permethrin from berries was further confirmed by TLC. [ABSTRACT FROM PUBLISHER]

Background: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood., Methods: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice., Results: HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16 + monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16 + monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice., Conclusions: These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16 + monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology., Competing Interests: None.

Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The proinflammatory signaling during different phases of CS is incompletely understood. We collected serum and plasma ( n = 44) as well as freshly isolated peripheral blood mononuclear cells (PBMCs, n = 7) of patients with CS complicating acute myocardial infarction on admission and after revascularization (24, 48, and 72 h) and of healthy controls (serum and plasma, n = 75; PBMCs, n = 12). PBMCs of patients with CS had increased gene expression of NLRP3 , CASP1 , PYCARD , IL1B , and IL18 and showed increased rates of pyroptosis (control, 4.7 ± 0.3 vs. 9.9 ± 1.7% in patients with CS, P = 0.02). Serum interleukin (IL)-1β levels were increased after revascularization. IL-18 and IL-6 were higher in patients with CS than in healthy controls but comparable before and after revascularization. Proinflammatory apoptosis-associated speck-like proteins containing CARD (ASC) specks were elevated in the serum of patients with CS on admission and increased after revascularization (admission, 11.1 ± 4.4 specks/µL; after 24 h, 19.0 ± 3.9, P = 0.02). ASC specks showed a significant association with 30-day mortality in patients with CS ( P < 0.05). The estimated regression coefficients and odds ratios indicated a positive relationship between ASC specks and mortality (odds ratio: 1.029, 95% confidence interval, 1.000 to 1.072; P = 0.02). Pyroptosis and circulating ASC specks are increased in patients with CS and are particularly induced after reperfusion. This underscores their potential role as a biomarker for poor outcomes in patients with CS. ASC specks represent promising new therapeutic targets for patients with CS with high inflammatory burden. NEW & NOTEWORTHY The expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome-related genes and the rate of pyroptosis are increased in PBMCs from patients with CS. Furthermore, patients with CS are characterized by higher serum concentrations of ASC specks and IL-1β, IL-6, and IL-18. This current study adds circulating ASC specks to the portfolio of biomarkers for the identification of patients with a high inflammatory burden paving the way for precision medicine approaches to improve clinical outcomes.

Introduction: The interleukin-1 (IL-1) family and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome contribute to atherogenesis but the underlying mechanisms are incompletely understood. Unlike IL-1β, IL-1α is not dependent on the NLRP3 inflammasome to exert its pro-inflammatory effects. Here, a non-genetic model was applied to characterize the role of IL-1α, IL-1β, and NLRP3 for the pathogenesis of atherosclerosis., Methods: Atherogenesis was induced by gain-of-function PCSK9-AAV8 mutant viruses and feeding of a high-fat western diet (WTD) for 12 weeks in C57Bl6/J wildtype mice (WT) and in Il1a -/- , Nlrp3 -/- , and Il1b -/- mice., Results: PCSK9-Il1a -/- mice showed reduced atherosclerotic plaque area in the aortic root with lower lipid accumulation, while no difference was observed between PCSK9-WT, PCSK9-Nlrp3 -/- and PCSK9-Il1b -/- mice. Serum proteomic analysis showed a reduction of pro-inflammatory cytokines (e.g., IL-1β, IL-6) in PCSK9-Il1a -/- as well as in PCSK9-Nlrp3 -/- and PCSK9-Il1b -/- mice. Bone marrow dendritic cells (BMDC) of PCSK9-WT, PCSK9-Nlrp3 -/- , and PCSK9-Il1b -/- mice and primary human monocytes showed translocation of IL-1α to the plasma membrane (csIL-1α) upon stimulation with LPS. The translocation of IL-1α to the cell surface was regulated by myristoylation and increased in mice with hypercholesterolemia. CsIL-1α and IL1R1 protein-protein interaction on endothelial cells induced VCAM1 expression and monocyte adhesion, which was abrogated by the administration of neutralizing antibodies against IL-1α and IL1R1., Conclusion: The results highlight the importance of IL-1α on the cell surface of circulating leucocytes for the development of atherosclerosis. PCSK9-Il1a -/- mice, but not PCSK9-Nlrp3 -/- or PCSK9-Il1b -/- mice, are protected from atherosclerosis after induction of hypercholesterolemia independent of circulating cytokines. Myristoylation and translocation of IL-1α to the cell surface in myeloid cells facilitates leukocyte adhesion and contributes to the development of atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maeder, Speer, Wirth, Boeckel, Fatima, Shahzad, Freichel, Laufs and Gaul.)

Background and Aims: Transient Elastography is a non-invasive, cost-efficient, non-ionizing, observer-independent and reliable method to detect liver fibrosis using Liver Stiffness Measurement (LSM) and the degree of fat accumulation in the liver using Controlled Attenuation Parameter (CAP). This study aims to derive reference values for both measures from healthy children and adolescents. Further, we aim to assess the potential influence of age, sex, puberty, and BMI-SDS on CAP and LSM., Methods: Within the LIFE Child study, amongst others, anthropometric data and pubertal status were assessed. Transient Elastography (TE) was performed using the FibroScan ® device in a population-based cohort at 982 study visits of 482 healthy children aged between 10 and 18 years. Percentiles for LSM and CAP were estimated, and the effects of age, sex, puberty and weight status were assessed through hierarchical regression models., Results: There was a strong age dependency for LSM with higher values for older children, most pronounced in the upper percentiles in boys. Contrarily, CAP was relatively stable across the age span without considerable difference between boys and girls. We found a significant positive correlation between BMI-SDS and both CAP and LSM for BMI-SDS >1.28. For BMI-SDS < 1.28, the association was also positive but reached statistical significance only for CAP. Further, the association between BMI-SDS and CAP was significantly stronger in younger than in older children. There was no association between pubertal status and CAP. For LSM, we found that children with a high BMI-SDS but not children with normal weight had significantly higher LSM values in Tanner stage 4., Conclusions: Age, sex, pubertal status and weight status should be considered when interpreting LSM and CAP in pediatric patients to facilitate and improve early detection of abnormal liver function, which is associated with common pathologies, such as NAFLD., Competing Interests: TK received unrestricted research grants from Echosens SA, France, not related to this project. TK took part in a clinical advisory board meeting of Echosens SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brunnert, Puasa, Garten, Penke, Gaul, Grafe, Karlas, Kiess, Flemming and Vogel.)

Background and Aims: The NOD-like receptor protein 3 (NLRP3) inflammasome is a central contributor to human acute and chronic liver disease, yet the molecular and cellular mechanisms by which its activation precipitates injury remain incompletely understood. Here, we present single cell transcriptomic profiling of livers from a global transgenic tamoxifen-inducible constitutively activated Nlrp3 A350V mutant mouse, and we investigate the changes in parenchymal and nonparenchymal liver cell gene expression that accompany inflammation and fibrosis., Approach and Results: Our results demonstrate that NLRP3 activation causes chronic extramedullary myelopoiesis marked by myeloid progenitors that differentiate into proinflammatory neutrophils, monocytes, and monocyte-derived macrophages. We observed prominent neutrophil infiltrates with increased Ly6g HI and Ly6g INT cells exhibiting transcriptomic signatures of granulopoiesis typically found in the bone marrow. This was accompanied by a marked increase in Ly6c HI monocytes differentiating into monocyte-derived macrophages that express transcriptional programs similar to macrophages of NASH models. NLRP3 activation also down-regulated metabolic pathways in hepatocytes and shifted hepatic stellate cells toward an activated profibrotic state based on expression of collagen and extracellular matrix regulatory genes., Conclusions: These results define the single cell transcriptomes underlying hepatic inflammation and fibrosis precipitated by NLRP3 activation. Clinically, our data support the notion that NLRP3-induced mechanisms should be explored as therapeutic target in NASH-like inflammation., (© 2022 American Association for the Study of Liver Diseases.)

Alterations of RNA editing that affect the secondary structure of RNAs can cause human diseases. We therefore studied RNA editing in failing human hearts. Transcriptome sequencing showed that adenosine-to-inosine (A-to-I) RNA editing was responsible for 80% of the editing events in the myocardium. Failing human hearts were characterized by reduced RNA editing. This was primarily attributable to Alu elements in introns of protein-coding genes. In the failing left ventricle, 166 circRNAs were upregulated and 7 circRNAs were downregulated compared to non-failing controls. Most of the upregulated circRNAs were associated with reduced RNA editing in the host gene. ADAR2, which binds to RNA regions that are edited from A-to-I, was decreased in failing human hearts. In vitro, reduction of ADAR2 increased circRNA levels suggesting a causal effect of reduced ADAR2 levels on increased circRNAs in the failing human heart. To gain mechanistic insight, one of the identified upregulated circRNAs with a high reduction of editing in heart failure, AKAP13, was further characterized. ADAR2 reduced the formation of double-stranded structures in AKAP13 pre-mRNA, thereby reducing the stability of Alu elements and the circularization of the resulting circRNA. Overexpression of circAKAP13 impaired the sarcomere regularity of human induced pluripotent stem cell-derived cardiomyocytes. These data show that ADAR2 mediates A-to-I RNA editing in the human heart. A-to-I RNA editing represses the formation of dsRNA structures of Alu elements favoring canonical linear mRNA splicing and inhibiting the formation of circRNAs. The findings are relevant to diseases with reduced RNA editing and increased circRNA levels and provide insights into the human-specific regulation of circRNA formation., (© 2022. The Author(s).)