SIMULATING HYDROGEN BONDED CLUSTERS AND ZEOLITE CLUSTERS FOR RENEWABLE ENERGY APPLICATIONS

Our research attention is focused on the development of new fuel cell membrane materials and new zeolites which improve biomass conversion rate to meet the increasing demand of renewable and sustainable energy. We have simulated the dynamics of amphiprotic groups (pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole, acetic acid, formic acid, sulfuric acid, and phosphoric acid) as neat liquids and tethered via linkers to aliphatic backbones, to determine how tethering and varying functional groups affect hydrogen bond networks and reorientation dynamics, both factors thought to influence proton conduction. We used the DL_Poly_2 molecular dynamics code with the GAFF force field to simulate tethered systems over the temperature range 200−900 K, and to simulate the corresponding neat liquids under liquid state temperatures at standard pressure. We computed hydrogen-bond cluster sizes; orientational order parameters and orientational correlation functions associated with functional groups, linkers, and backbones; and time scales and activation energies associated with orientational randomization. Regarding neat phosphoric acid, we find that anomalously large hydrogen-bond clusters provide a neutral-system signature of the high experimental proton conductivity in neat phosphoric acid. Regarding tethered oligomer systems, all exhibited a liquid to glassy-solid transition upon cooling, with the formic-, and acetic-based oligomers retaining liquid behavior to relatively low temperatures (~400 K); while azoles- and phosphonic-oligomers formed glassy solids around 500-600 K; and sulfonic-pentamers lost motion around 900 K as evidenced by orientational order parameters and correlation functions. Hydrogen bond cluster sizes in tethered phosphonic acid (T ≤ 500 K) remain orders of magnitude above all other tethered systems, suggesting tethered phosphonic oligomers as promising targets for new PEMs. Tethering the azoles was generally found to produce hydrogen-bond cluster sizes similar to those in untethered liquids, and to produce longer hydrogen-bond lifetimes than those in liquids. The simulated rates of functional group reorientation decreased dramatically upon tethering. The activation energies associated with orientational randomization agree well with NMR data for tethered imidazole systems at lower temperatures, and for tethered 1,2,3-triazole systems at both low- and high-temperature ranges. Overall, our simulations corroborate the notion that tethering functional groups dramatically slows the process of reorientation. We found a linear correlation between gas-phase hydrogen-bond energies and tethered-functional-group reorientation barriers for all azoles except for imidazole, which acts as an outlier because of both atomic charges and molecular structure. We have performed density functional theory (DFT) calculations to investigate the convergence of reaction barriers with respect to zeolite cluster size, for multi-step reactions catalyzed in HZSM-5 zeolite. We have constructed cluster models of HZSM-5 using the delta-cluster approach reported previously by us [ACS Catalysis 5, 2859 (2015)], which systematically treats zeolite confinement using a single neighbor-list radius. We computed barriers for several different reaction types, and with a range of reactant sizes from 2 to 13 heavy (non-hydrogen) atoms, to determine the cluster sizes and neighbor-list radii needed to fully treat zeolite confinement effects. To establish barrier convergence, we studied the acid-zeolite-catalyzed aldol reactions of acetone with aldehydes of increasing size (formaldehyde, furfural, and hydroxymethyl-furfural), modeling the acid-catalyzed aldol reaction in three steps: keto/enol tautomerization of acetone, bimolecular combination between each aldehyde and the enol, and aldol dehydration. We found that the delta cluster neighbor-list radius of 4 Å is sufficient to converge barriers with respect to cluster size for all reaction steps considered, yielding complete treatments of confinement in HZSM-5 with clusters containing up to 99 (Si, Al, O) framework atoms. For comparison, periodic DFT calculations on HZSM-5 include 288 framework atoms, requiring 19 times more CPU time in our head-to-head comparisons on a single processor. The converged acetone/formaldehyde dehydration barrier from our cluster calculations agrees quantitatively with a comparable barrier obtained by Curtiss and coworkers with periodic DFT, showing that cluster calculations can converge properties with respect to system size at a fraction of the cost of periodic DFT. Interestingly, we found that the bulkier, furan-containing aldehydes exhibit faster aldol reactivity because of charge delocalization from their aromatic rings, which significantly speeds up aldol dehydration

Caenorhabditis elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-Induced Apoptosis

Arginine methylation of histone and non-histone proteins is involved in transcription regulation and many other cellular processes. Nevertheless, whether such protein modification plays a regulatory role during apoptosis remains largely unknown. Here we report that the Caenorhabditis elegans homolog of mammalian type II arginine methyltransferase PRMT5 negatively regulates DNA damage-induced apoptosis. We show that inactivation of C. elegans prmt-5 leads to excessive apoptosis in germline following ionizing irradiation, which is due to a CEP-1/p53–dependent up-regulation of the cell death initiator EGL-1. Moreover, we provide evidence that CBP-1, the worm ortholog of human p300/CBP, functions as a cofactor of CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter. Importantly, down-regulation of cbp-1 significantly suppresses DNA damage-induced egl-1 expression and apoptosis in prmt-5 mutant worms. These findings suggest that PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1, which represents a novel regulatory mechanism of p53-dependent apoptosis

H9N2 Viruses Isolated From Mammals Replicated in Mice at Higher Levels Than Avian-Origin Viruses

H9N2 subtype influenza A virus (IAV) has more than 20 genotypes that are able to cross species barriers and expand from birds to mammals and humans. To better understand the impact of different H9N2 genotypes and their characteristics, five H9N2 viruses from different hosts including chickens, geese, pigs, mink, and humans representing the B69 88(Gs/14, Ck/15, and Mi/14), B35 (Sw/08) and G9 genotypes (Hu/04) were infected in chicken and mice. In mice, mammal-origin viruses replicated at higher levels in the lungs compared to avian viruses. The goose-virus replicated at the lowest levels indicating poor adaptation. Increased pro-inflammatory cytokines were positively correlated with viral loads in the lung. In chickens, all viruses were excreted from cloacal and/or oropharyngeal swabs. Interestingly, Mink-origin virus exhibited higher virulence and replication in mice and chickens. Our data indicate that mammal-origin H9N2 viruses are more adapted and virulent in mice than the avian-origin viruses

Curcumin protects mice with myasthenia gravis by regulating the gut microbiota, short-chain fatty acids, and the Th17/Treg balance

Curcumin is widely used as a traditional drug in Asia. Interestingly, curcumin and its metabolites have been demonstrated to influence the microbiota. However, the effect of curcumin on the gut microbiota in patients with myasthenia gravis (MG) remains unclear. This study aimed to investigate the effects of curcumin on the gut microbiota community, short-chain fatty acids (SCFAs) levels, intestinal permeability, and Th17/Treg balance in a Torpedo acetylcholine receptor (T-AChR)-induced MG mouse model. The results showed that curcumin significantly alleviated the clinical symptoms of MG mice induced by T-AChR. Curcumin modified the gut microbiota composition, increased microbial diversity, and, in particular, reduced endotoxin-producing Proteobacteria and Desulfovibrio levels in T-AChR-induced gut dysbiosis. Moreover, we found that curcumin significantly increased fecal butyrate levels in mice with T-AChR-induced gut dysbiosis. Butyrate levels increased in conjunction with the increase in butyrate-producing species such as Oscillospira, Akkermansia, and Allobaculum in the curcumin-treated group. In addition, curcumin repressed the increased levels of lipopolysaccharide (LPS), zonulin, and FD4 in plasma. It enhanced Occludin expression in the colons of MG mice induced with T-AChR, indicating dramatically alleviated gut permeability. Furthermore, curcumin treatment corrected T-AChR-induced imbalances in Th17/Treg cells. In summary, curcumin may protect mice against myasthenia gravis by modulating both the gut microbiota and SCFAs, improving gut permeability, and regulating the Th17/Treg balance. This study provides novel insights into curcumin's clinical value in MG therapy

Structural Heterogeneity in the Collision Complex between Organic Dyes and Tryptophan in Aqueous Solution

The heterogeneity on photoinduced electron transfer (PET) kinetics between a labeled fluorophore and an amino acid residue has been extensively studied in biopolymers. However in aqueous solutions, the heterogeneity on PET kinetics between a fluorophore and a quencher has rarely been reported. Herein, we selected four commonly used fluorophores, such as tetramethylrhodamine (TMR), Rhodamine B (RhB), Alexa fluor 546 (Alexa546), and Atto655, and studied their respective PET kinetics in 50 mM tryptophan solutions with femtosecond transient absorption spectroscopy to explore the structural heterogeneity in their corresponding collision complexes. We measured the decay of the first excited electronic state of respective fluorophore with and without 50 mM tryptophan in aqueous solutions, and derived the charge separation rate in their corresponding collision complexes. We found that the PET process of all selected fluorophores in 50 mM tryptophan solutions has two charge separation rates, which indicates that the relevant states in the collision complex between respective fluorophore and tryptophan have strong structural heterogeneity. These femtosecond PET measurements are in agreement with Vaiana’s molecular dynamics simulation (<i>J. Am. Chem. Soc.</i> <b>2003</b>, <i>125</i>, 14564). In addition, with the obtained PET kinetic parameters, we derived the relative brightness of the collision complex between respective fluorophore and tryptophan, which are important parameters for the PET based fluorescence correlation spectroscopy study involving these fluorophores in biopolymers

Sodium butyrate alleviates R97-116 peptide-induced myasthenia gravis in mice by improving the gut microbiota and modulating immune response

Abstract Fermented butyrate exhibits an anti-inflammatory response to maintain immune homeostasis within the gut. However, the effect and underlying mechanism of butyrate on myasthenia gravis (MG) remain unclear. The changes in the gut microbiota and fecal contents of SCFAs in MG patients were examined. R97-116 peptide was used to induce the experimental autoimmune myasthenia gravis (EAMG) mice and sodium butyrate (NaB) was gavaged to the EAMG mice. Gut microbiota, the frequency of Th1, Th17, Treg, Tfh, and B cells, the levels of IFN-γ, IL-17 A, IL-10, IL-21, and anti-R97-116 IgG, RNA-seq of total B cells in the spleen were explored by metagenomics, flow cytometry, ELISA, and transcriptomics. A significant reduction in SCFA-producing bacteria including Butyricimonas synergistica and functional modules including butyrate synthesis/production II was observed in MG patients and fecal SCFAs detection confirmed the increase. The EAMG mice were successfully constructed and NaB supplementation has changed the composition and function of the gut microbiota. The numbers of Th1, Th17, Tfh, and B cells were significantly increased while that of Treg cells was obviously decreased in EAMG mice compared with controls. Interestingly, NaB treatment has reduced the amounts of Th17, Tfh, and B cells but increased that of Treg cells. Accordingly, the levels of IL-17 A, IL-21, and IgG were increased while IL-10 was decreased in EAMG mice. However, NaB treatment reduced IL-17 A and IL-21 but increased that of IL-10. RNA-seq of B cells has revealed 4577 deferentially expressed genes (DEGs), in which 1218 DEGs were up-regulated while 3359 DEGs were down-regulated in NaB-treated EAMG mice. GO enrichment and KEGG pathway analysis unveiled that the function of these DEGs was mainly focused on immunoglobulin production, mitochondrial respiratory chain complex, ribosome, oxidative phosphorylation, and CNS diseases including amyotrophic lateral sclerosis. We have found that butyrate was significantly reduced in MG patients and NaB gavage could evidently improve MG symptoms in EAMG mice by changing the gut microbiota, regulating the immune response, and altering the gene expression and function of B cells, suggesting NaB might be a potential immunomodulatory supplement for MG drugs

METTL14 enhances the m6A modification level of lncRNA MSTRG.292666.16 to promote the progression of non-small cell lung cancer

Abstract Background m6A modification has close connection with the occurrence, development, and prognosis of tumors. This study aimed to explore the roles of m6A modification and its related mechanisms in non-small cell lung cancer (NSCLC). Methods NSCLC tissues and their corresponding para-cancerous tissues were collected to determine the m6A levels of total RNA/lncRNAs and the expression of m6A modification-related genes/lncRNAs. Then, A549 cells were transfected with si-METTL14 or oe-METTL14, and the cell transfection efficiency was assessed. Subsequently, the viability, apoptosis, cell colony formation, migration and invasion of the different cells were determined. Finally, the nude mouse tumorigenicity experiments were performed to observe the effects of METTL14 in vivo. Results Compared to the para-NSCLC tissues, the m6A level and METTL14 expression were both significantly increased in the NSCLC tissues (P < 0.05). Based on the expression of METTL14 in the different cell lines, A549 cells were chosen for further experiments. Then, the A549 cells with METTL14 knockdown and overexpression were successfully established, as well as it was found that METTL14 knockdown could inhibit the viability, colony formation, migration, and invasion of A549 cells, while facilitate their apoptosis. In vivo experiments also showed that METTL14 knockdown could inhibit tumor formation and growth. Additionally, the m6A level of MSTRG.292666.16 was higher in the NSCLC tissues; and after METTL14 knockdown, the expression and m6A level of MSTRG.292666.16 were both significantly reduced in A549 cells, and vice versa. Conclusion METTL14 may promote the progression of NSCLC through up-regulating MSTRG.292666.16 and enhance its m6A modification level