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Lipid peroxides result from a reaction between cis-unsaturated lipid chains and singlet oxygen molecules leading to the addition of a peroxide OOH side group next to the acyl-chain double bond. It is now established that HP-POPC (hydroperoxidized POPC) molecules form stable, thin, and laterally expanded bilayers. The difference in the structural organization arises from the hydrophilic character of the OOH side group that has a strong affinity with the water interface region, leading to significant reorganization of the bilayer. In this article, we describe a coarse-grained (CG) model of POPC and DOPC lipid peroxides within the framework of the Martini CG force-field (v2.2), derived from experimental data. We then discuss extensively the predicted structure and the influence of hydration and show how shifting the position of the unsaturated bonds along the chain changes the structure. Finally, we provide electron and neutron scattering length density profiles of the simulated bilayers. [ABSTRACT FROM AUTHOR]

Summary: MicroRNA168 (MIR168) is a key miRNA that targets the main RNA‐induced silencing complex component Argonaute 1 (AGO1) to regulate plant growth and environmental stress responses. However, the regulatory functions of MIR168 need to be further elucidated in rice. In this paper, we generated clean OsMIR168a deletion mutants by CRISPR‐Cas9 strategy. We then phenotypically and molecularly characterized these mutants. The rice OsMIR168a mutants grew rapidly at the seedling stage, produced more tillers and matured early. Compared to the wild‐type plants, the mutants were shorter at maturity and produced smaller spikelets and seeds. Analysis of gene expression showed that the transcription levels of OsMIR168a's target genes such as OsAGO1a, OsAGO1b and OsAGO1d were elevated significantly in the OsMIR168a mutants. Intriguingly, OsAGO18, a member of a new AGO clade that is conserved in monocots, was confirmed to be a target of OsMIR168a not only by informatic prediction but also by expression analysis and a cell‐based cleavage assay in the OsMIR168a mutants. Many protein‐coding genes and miRNAs showed differential expression in the OsMIR168a mutants, suggesting OsMIR168a exerts a major transcriptional regulatory role, likely through its potential target genes such as OsAGO1s and OsAGO18. KEGG enrichment analysis of these differentially expressed genes pointed to OsMIR168a's involvement in important processes such as plant hormone signalling transduction and plant–pathogen interaction. These data collectively support that the complex regulation module of OsMIR168a‐OsAGO1/OsAGO18‐miRNAs‐target genes contributes to agronomically important traits, which sheds light on miRNA‐mediated crop breeding. [ABSTRACT FROM AUTHOR]

Most human diseases are accompanied by systems changes. Systems biomarkers should reflect such changes. The phosphorylation and dephosphorylation of biomolecules maintain human homeostasis. However, the systems biomarker characteristics of circulating alkaline phosphatase, a routine blood test conducted for many human diseases, have never been investigated. This study retrieved the circulating alkaline phosphatase (ALP) activities from patients with 48 clinically confirmed diseases and healthy individuals from the database of our hospital during the past five years. A detailed analysis of the statistical characteristics of ALP was conducted, including quantiles, receiving operator curve (ROC), and principal component analysis. Among the 48 diseases, 45 had increased, and three had decreased median levels of ALP activities compared to the healthy control. Preeclampsia, hepatic encephalopathy, pancreatic cancer, and liver cancer had the highest median values, whereas nephrotic syndrome, lupus erythematosus, and nephritis had decreased median values compared to the healthy control. Further, area under curve (AUC) values were ranged between 0.61 and 0.87 for 19 diseases, and the ALP activities were the best systems biomarker for preeclampsia (AUC 0.87), hepatic encephalopathy (AUC 0.87), liver cancer (AUC 0.81), and pancreatic cancer (AUC 0.81). Alkaline phosphatase was a decent systems biomarker for 19 different types of human diseases. Understanding the molecular mechanisms of over-up-and-down-regulation of ALP activities might be the key to understanding the whole-body systems' reactions during specific disease progression. [ABSTRACT FROM AUTHOR]

Periodontal defect regeneration in severe periodontitis relies on the differentiation and proliferation of periodontal ligament cells (PDLCs). Recently, an emerging 2D nanomaterial, MXene (Ti 3 C 2 T x ), has gained more and more attention due to the extensive antibacterial and anticancer activity, while its potential biomedical application on tissue regeneration remains unclear. Through a combination of experimental and multiscale simulation schemes, Ti 3 C 2 T x has exhibited satisfactory biocompatibility and induced distinguish osteogenic differentiation of human PDLCs (hPDLCs), with upregulated osteogenesis-related genes. Ti 3 C 2 T x manages to activate the Wnt/β-catenin signaling pathway by enhancing the Wnt-Frizzled complex binding, thus stabilizing HIF-1α and altering metabolic reprogramming into glycolysis. In vivo, hPDLCs pretreated by Ti 3 C 2 T x display excellent performance in new bone formation and osteoclast inhibition with enhanced RUNX2, HIF-1α, and β-catenin in an experimental rat model of periodontal fenestration defects, indicating that this material has high efficiency of periodontal regeneration promotion. It is demonstrated in this work that Ti 3 C 2 T x has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)