Composite Modeling and Analysis of FDM Prototypes for Design and Fabrication of Functionally Graded Parts

Solid Freeform Fabrication technologies have potential to manufacture parts with locally controlled properties (LCP), which would allow concurrent design of part’s geometry and desired properties. To a certain extent, Fused Deposition Modelling (FDM) has the ability to fabricate parts with LCP by changing deposition density and deposition orientation. To fully exploit this potential, this paper reports a study on the mechanical properties of FDM prototypes, and related materials and fabrication process issues. Both theoretical and experimental analyses of mechanical properties of FDM parts were carried out. To establish the constitutive models, a set of equations is proposed to determine the elastic constants of FDM prototypes. An example is provided to illustrate the model with LCP using FDM.The financial support for this research was provided by the National Sciences and Engineering Research Council of Canada (NSERC) through Research Grant OGP0192173.Mechanical Engineerin

Gab2 facilitates epithelial-to-mesenchymal transition via the MEK/ERK/MMP signaling in colorectal cancer

Clinicopathologic factors and Gab2 expression in 35 CRC patients. (DOCX 22 kb

ChIP-seq identifies McSLC35E2 as a novel target gene of McNrf2 in Mytilus coruscus, highlighting its role in the regulation of oxidative stress response in marine mollusks

NF-E2-related factor 2 (Nrf2) plays a crucial role in the oxidative regulatory process, which could trigger hundreds of antioxidant elements to confront xenobiotics. In the previous study, we identified Nrf2 from the marine mussel Mytilus coruscus, and the findings demonstrated that McNrf2 effectively protected the mussels against oxidative stress induced by benzopyrene (Bap). In order to delve deeper into the underlying mechanism, we utilized Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) technology to systematically identify potential novel target genes of McNrf2. A total of 3,465 potential target genes were screened, of which 219 owned binding sites located within the promoter region. During subsequent experimental verification, it was found that McSLC35E2, a candidate target gene of McNrf2, exhibited negative regulation by McNrf2, as confirmed through dual luciferase and qRT-PCR detection. Further, the enzyme activity tests demonstrated that McNrf2 could counteract Bap induced oxidative stress by inhibiting McSLC35E2. The current study provides valuable insights into the application of ChIP-seq technology in the research of marine mollusks, advancing our understanding of the key role of Nrf2 in antioxidant defense mechanisms, and highlighting the significance of SLC35E2 in the highly sophisticated regulation of oxidative stress response in marine invertebrates

Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity: Characterization and evaluation

AbstractVancomycin hydrochloride （VANH）, the first glycopeptide antibiotic, is a water-soluble drug for the treatment of acute osteomyelitis. Liposomal formulations of VANH have already been manipulated and characterized, which was a mean of increasing their therapeutic index, reducing their toxicity and altering drug biodistribution. One of the challenges for preparing VANH-Lips is their low encapsulation efficiency (EE). In the present study, we aim to improve the liposomal formulation of VANH for higher EE, longer systemic circulation, reduced nephrotoxicity and enhanced antimicrobial activities. Vancomycin hydrochloride-loaded liposomes (VANH-Lips) were formulated by the method of modified reverse phase evaporation. Based on the optimization of formulation with orthogonal experimental design, the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78 ± 2.56% and 188.4 ± 2.77 nm. In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation. After intravenous injection to mice, the mean residence time (MRT) of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution (VANH-Sol) group. Furthermore, the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection. In conclusion, VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis

The relationship between atrial fibrillation and NLRP3 inflammasome: a gut microbiota perspective

Atrial fibrillation (AF) is a common clinical arrhythmia whose pathogenesis has not been fully elucidated, and the inflammatory response plays an important role in the development of AF. The inflammasome is an important component of innate immunity and is involved in a variety of pathophysiologic processes. The NLRP3 inflammasome is by far the best studied and validated inflammasome that recognizes multiple pathogens through pattern recognition receptors of innate immunity and mediates inflammatory responses through activation of Caspase-1. Several studies have shown that NLRP3 inflammasome activation contributes to the onset and development of AF. Ecological dysregulation of the gut microbiota has been associated with the development of AF, and some evidence suggests that gut microbiota components, functional byproducts, or metabolites may induce or exacerbate the development of AF by directly or indirectly modulating the NLRP3 inflammasome. In this review, we report on the interconnection of NLRP3 inflammasomes and gut microbiota and whether this association is related to the onset and persistence of AF. We discuss the potential value of pharmacological and dietary induction in the management of AF in the context of the association between the NLRP3 inflammasome and gut microbiota. It is hoped that this review will lead to new therapeutic targets for the future management of AF

Loss of Microstructural Integrity in the Limbic-Subcortical Networks for Acute Symptomatic Traumatic Brain Injury

Previous studies reported discrepant white matter diffusivity in mild traumatic brain injury (mTBI) on the base of Glasgow Coma Scale, which are unreliable for some TBI severity indicators and the frequency of missing documentation in the medical record. In the present study, we adopted the Mayo classification system for TBI severity. In this system, the mTBI is also divided into two groups as "probable and symptomatic" TBI. We aimed to investigate altered microstructural integrity in symptomatic acute TBI (<1 week) by using tract-based spatial statics (TBSS) approach. A total of 12 patients and 13 healthy volunteers were involved and underwent MRI scans including conventional scan, and SWI and DTI. All the patients had no visible lesions by using conventional and SWI neuroimaging techniques, while showing widespread declines in the fractional anisotropy (FA) of gray matter and white matter throughout the TBSS skeleton, particularly in the limbic-subcortical structures. By contrast, symptomatic TBI patients showed no significant enhanced changes in FA compared to the healthy controls. A better understanding of the acute changes occurring following symptomatic TBI may increase our understanding of neuroplasticity and continuing degenerative change, which, in turn, may facilitate advances in management and intervention

Analysis and fabrication of FDM prototypes with locally controlled properties

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ATP Binding and Channel Activation in P2X Receptors

Purinergic P2X receptors are a family of nonselective cation channels gated by extracellular adenosine 5′-triphosphate. They are important drug targets primarily because of their involvement in neuropathic pain and inflammation. ATP binds allows Na+ and Ca2+ to pass through the channel pore, thus causing membrane depolarization and affecting various downstream Ca2+-dependent signaling processes. A concerted effort by investigators over the last two decades has culminated in significant advances in our understanding of where ATP binds and how ATP binding leads to channel opening and ion flux. The recent publication of the crystal structures for both the closed and open channel conformations of the zebrafish P2X4 receptor sheds new light on how P2X receptors work. In this review, we will attempt to present the existing functional data regarding ATP binding with the available crystal structure data and different experimental approaches that have been used to explore the ATP-binding sites