From development to diseases: The role of 5hmC in brain

AbstractEpigenetic modulations play essential roles in diverse biological processes. During the past several years, DNA demethylation has been discovered in embryonic and postnatal development. Although some potential functions of DNA methylation have been demonstrated already, many questions remain in terms of unveiling the role of 5hmC; whether it serves either merely as an intermediate of DNA demethylation or as a stable epigenetic marker. 5-hydroxymethylcytosine (5hmC) is proved to be not merely serving as an intermediate of DNA demethylation, but also acts as a stable epigenetic marker. This review summarizes the current knowledge of the function of 5hmC in brain with the focus on the neuronal activity, neurodevelopment, aging, and neurological diseases

Long Non-coding RNA in Neuronal Development and Neurological Disorders

Long non-coding RNAs (lncRNAs) are transcripts which are usually more than 200 nt in length, and which do not have the protein-coding capacity. LncRNAs can be categorized based on their generation from distinct DNA elements, or derived from specific RNA processing pathways. During the past several decades, dramatic progress has been made in understanding the regulatory functions of lncRNAs in diverse biological processes, including RNA processing and editing, cell fate determination, dosage compensation, genomic imprinting and development etc. Dysregulation of lncRNAs is involved in multiple human diseases, especially neurological disorders. In this review, we summarize the recent progress made with regards to the function of lncRNAs and associated molecular mechanisms, focusing on neuronal development and neurological disorders

Synthesis and antibacterial activity evaluation of aminoguanidine or dihydrotriazine derivatives

301-308In the alarming context of rising bacterial antibiotic resistance, there is an urgent need to discover new antibiotics or increase and/or enlarge the activity of those currently in use. In this article, aminoguanidine and dihydrotriazine derivatives were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities. Most of the synthesized compounds showed potent inhibitory activities against different bacteria and one fungus with minimum inhibitory concentrations (MICs) ranging from 1 to 64 μg/mL, which obviously better than the positives control drug. The compound 23a showed the best antibacterial activities, whose MIC value was 1 μg/mL against eight strains. The cytotoxic activity of the compound 4c, 8a and 23a were assessed in Human liver cancer cells. The preliminary docking results imply that compounds 21b and 23a possibly display their antibacterial activity through the interaction with DHFR protein by targeting residues of the active cavities of DHFR

Synthesis and antibacterial activity evaluation of aminoguanidine or dihydrotriazine derivatives

In the alarming context of rising bacterial antibiotic resistance, there is an urgent need to discover new antibiotics or increase and/or enlarge the activity of those currently in use. In this article, aminoguanidine and dihydrotriazine derivatives were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities. Most of the synthesized compounds showed potent inhibitory activities against different bacteria and one fungus with minimum inhibitory concentrations (MICs) ranging from 1 to 64 μg/mL, which obviously better than the positives control drug. The compound 23a showed the best antibacterial activities, whose MIC value was 1 μg/mL against eight strains. The cytotoxic activity of the compound 4c, 8a and 23a were assessed in Human liver cancer cells. The preliminary docking results imply that compounds 21b and 23a possibly display their antibacterial activity through the interaction with DHFR protein by targeting residues of the active cavities of DHFR

Optimization and Simulation of an Evolving Kidney Paired Donation (KPD) Program

The old concept of barter exchange has extended to the modern area of living-donor kidney transplantation, where one incompatible donor-candidate pair is matched to another pair with a complementary incompatibility, such that the donor from one pair gives an organ to a compatible candidate in the other pair and vice versa. Kidney paired donation (KPD) programs provide a unique and important platform for living incompatible donor-candidate pairs to exchange organs in order to achieve mutual benefit. We propose a novel approach to organizing kidney exchanges in an evolving KPD program with advantages, including (i) it allows for a more exible utility-based evaluation of potential kidney transplants; (ii) it takes into consideration stochastic features in managing a KPD program; and (iii) it exploits possible alternative exchanges when the originally planed allocation cannot be fully executed. Another primary contribution of this work is rooted in the development of a comprehensive microsimulation system for simulating and studying various aspects of an evolving KPD program. Various allocations can be obtained using integer programming (IP) techniques and microsimulation models can allow tracking of the evolving KPD over a series of match runs to evaluate different allocation strategies. Simulation studies are provided to illustrate the proposed method

X-ray tomography-assisted study of a phase inversion process in ceramic hollow fiber systems – Towards practical structural design

Phase inversion-assisted extrusion processes provide a feasible approach for the development of micro-structured ceramic hollow fibers. The mass transport of the hollow fiber, which is closely correlated to the pore structure, is especially important in the application of fuel cell electrodes and membrane reactors. Whilst the relationship between the pore microstructure and the fabrication factors has been the subject of significant investigations, there remains much disagreement in the literature. Recent development in X-ray computed tomography (CT) has enabled new insight into 3D microstructures, which could help to realize practical morphology design and optimization. In this study, a series of alumina hollow fibers have been prepared with varied polymer binder (polyethersulfone, PESf) concentration and new polymer-based internal coagulant (aqueous solution of polyvinyl alcohol, PVA). For the first time, the micro-channels were characterized in 3D using X-ray CT to determine micro-channel densities and diameters in the radial direction, as well as the 2D measurement of the pore size in the sponge-like layer. Water permeation tests were then conducted to correlate the micro-structure of the hollow fiber to the permeability. Results show that the diameter of the micro-channels decreases as the concentration of polymer binder increases, but the pore size in the spongy-like layer becomes larger. When the polymer binder concentration is increased from 16 wt% to 30 wt%, the maximum micro-channel diameter is almost halved (from 29 to 15 µm), and the radial length is 60% longer, whereas the mean flow pore size in the sponge-like layer is increased from approximately 288 to 422 nm. Larger pore size in the spongy-like layer of the high PVA concentration sample contributes to a better permeability (pure water flux almost doubled), but the dimension of the micro-channels is less important. This study provides a new approach to optimize fabrication of hollow fibers for various applications

Regulatory mechanism of ferroptosis, a new mode of cell death

Ferroptosis is a newly discovered process of cell death that differs from apoptosis, autophagy, and pyroptosis. It is closely related to tumor formation, diseases that damage tissue, and neurodegenerative diseases. Activation of the extracellular regulated protein kinase (EPK) pathway and acylCOA synthetase long-chain family member 4 (ACSL4) are indicative of ferroptosis. During ferroptosis, the mitochondrial volume becomes smaller and the double membrane density increases. The process of ferroptosis involves disruption of the material redox reaction, and changes in the levels of cystine, glutathione, NADPH, and increase of GPX4, NOX, and ROS. Iron increases significantly in ferroptosis. Divalent iron ions can greatly promote lipid oxidation, ROS accumulation, and thus promote ferroptosis. The occurrence and progress of ferroptosis are influenced by multiple factors and signaling pathways.Keywords: Ferroptosis, Iron; Lipid, Active oxygen, Inhibitor, Induce