001), has_circ_0070186 up-regulation (2.82-fold, P less then 0.001), and has_circ_0069972 down-regulation (0.50-fold, P less then 0.05). A functional analysis of these differentially expressed circRNAs suggests that they are associated with hypertrophy, remodeling, fibrosis, and autoimmunity. CircRNAs have been implicated in PDCM through largely unknown mechanisms. Here we report differentially expressed circRNAs in PDCM patients that may illuminate the mechanistic roles in the etiology of PDCM that could serve as non-invasive diagnostic biomarkers.Network theory-based approaches provide valuable insights into the variations in global structural connectivity between different dynamical states of proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of subtle conformational changes. We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using side-chain-based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational changes between the closed and partially open states of the SARS-CoV-2 spike protein. These conformational changes in the spike protein is crucial for coronavirus entry and fusion into human cells. Our analysis reveals global structural reorientations between the two states of the spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in the structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally, we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance drug design strategies.Here we show the novel anti-helminthic potential of Lansium parasiticum aqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasite Haemonchus contortus. LAgNPs showed LD50 values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50 value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metabolism. The results give rise to the opportunity for the development of alternative treatment for drug-resistant parasitic worms.Mechanical injury to the articular cartilage is a key risk factor in joint damage and predisposition to osteoarthritis. Integrative multi-omics approaches provide a valuable tool to understand tissue behavior in response to mechanical injury insult and help to identify key pathways linking injury to tissue damage.  https://www.selleckchem.com/products/c-178.html  Global or untargeted metabolomics provides a comprehensive characterization of the metabolite content of biological samples. In this study, we aimed to identify the metabolic signature of cartilage tissue post injury. We employed an integrative analysis of transcriptomics and global metabolomics of murine epiphyseal hip cartilage before and after injury. Transcriptomics analysis showed a significant enrichment of gene sets involved in regulation of metabolic processes including carbon metabolism, biosynthesis of amino acids, and steroid biosynthesis. Integrative analysis of enriched genes with putatively identified metabolite features post injury showed a significant enrichment for carbohydrate metabolism (glycolysis, galactose, and glycosylate metabolism and pentose phosphate pathway) and amino acid metabolism (arginine biosynthesis and tyrosine, glycine, serine, threonine, and arginine and proline metabolism). We then performed a cross analysis of global metabolomics profiles of murine and porcine ex vivo cartilage injury models. The top commonly modulated metabolic pathways post injury included arginine and proline metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and vitamin B6 metabolic pathways. These results highlight the significant modulation of metabolic responses following mechanical injury to articular cartilage. Further investigation of these pathways would provide new insights into the role of the early metabolic state of articular cartilage post injury in promoting tissue damage and its link to disease progression of osteoarthritis.Brain iron dyshomeostasis is a feature of Alzheimer's disease. Conventionally, research has focused on non-heme iron although degradation of heme from hemoglobin subunits can generate iron to augment the redox-active iron pool. Hemopexin both detoxifies heme to maintain iron homeostasis and bolsters antioxidant capacity via catabolic products, biliverdin and carbon monoxide to combat iron-mediated lipid peroxidation. The aim of the present study was to examine the association of cerebrospinal fluid levels (CSF) hemopexin and hemoglobin subunits (α and β) to Alzheimer's pathological proteins (amyloid and tau), hippocampal volume and metabolism, and cognitive performance. We analyzed baseline CSF heme/iron proteins (multiplexed mass spectrometry-based assay), amyloid and tau (Luminex platform), baseline/longitudinal neuroimaging (MRI, FDG-PET) and cognitive outcomes in 86 cognitively normal, 135 mild-cognitive impairment and 66 Alzheimer's participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort. Multivariate regression analysis was performed to delineate differences in CSF proteins between diagnosis groups and evaluated their association to amyloid and tau, neuroimaging and cognition. A p-value ≤ 0.05 was considered significant. Higher hemopexin was associated with higher CSF amyloid (implying decreased brain amyloid deposition), improved hippocampal metabolism and cognitive performance. Meanwhile, hemoglobin subunits were associated with increased CSF tau (implying increased brain tau deposition). When dichotomizing individuals with mild-cognitive impairment into stable and converters to Alzheimer's disease, significantly higher baseline hemoglobin subunits were observed in the converters compared to non-converters. Heme/iron dyshomeostasis is an early and crucial event in AD pathophysiology, which warrants further investigation as a potential therapeutic target.