Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response.

Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3 UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA

Bio-material polylactic acid/poly(butylene adipate-co-terephthalate) blend developed for extrusion- based additive manufacturing

Bio-material polylactic acid and poly(butylene adipate-co-terephthalate) were blended to achieve increased ductility of the blend. Cloisite was added to improve the stiffness of the blend. The blends were made into filament suitable for extrusion-based additive manufacturing. Melt flow index of the filament and mechanical properties of the printed bars were tested. Preliminary results showed that the melt flow index increases significantly with cloisite and the modulus of polylactic acid/poly(butylene adipate-co-terephthalate) improved slightly. The notched impact strength of the blend increased with increasing content of cloisite, and it increased significantly after annealing, especially for blends without cloisite

The transferability and design of commercial printer settings in PLA/PBAT fused filament fabrication

In many fused filament fabrication (FFF) processes, commercial printers are used, but rarely are printer settings transferred from one commercial printer to the other to give similar final tensile part performance. Here, we report such translation going from the Felix 3.0 to Prusa i3 MK3 printer by adjusting the flow rate and overlap of strands, utilizing an in-house developed blend of polylactic acid (PLA) and poly(butylene adipate-co-terephthalate) (PBAT). We perform a sensitivity analysis for the Prusa printer, covering variations in nozzle temperature, nozzle diameter, layer thickness, and printing speed (T-nozzle, d(nozzle), LT, and v(print)), aiming at minimizing anisotropy and improving interlayer bonding. Higher mass, larger width, and thickness are obtained with larger d(nozzle), lower v(print), higher LT, and higher T-nozzle. A higher v(print) results in less tensile strain at break, but it remains at a high strain value for samples printed with d(nozzle) equal to 0.5 mm. v(print) has no significant effect on the tensile modulus and tensile and impact strength of the samples. If LT is fixed, an increased d(nozzle) is beneficial for the tensile strength, ductility, and impact strength of the printed sample due to better bonding from a wider raster structure, while an increased LT leads to deterioration of mechanical properties. If the ratio d(nozzle)/LT is greater than 2, a good tensile performance is obtained. An improved T-nozzle leads to a sufficient flow of material, contributing to the performance of the printed device. The considerations brought forward result in a deeper understanding of the FFF process and offer guidance about parameter selection. The optimal d(nozzle)/v(print)/LT/T-nozzle combination is 0.5 mm/120 mm s(-1)/0.15 mm/230 degrees C

Bio-material polylactic acid/poly(butylene adipate-co-terephthalate) blend development for extrusion-based additive manufacturing

Bio-material polylactic acid and poly(butylene adipate-co-terephthalate) were blended to achieve increased ductility of the blend. Cloisite was added to improve the stiffness of the blend. The blends were made into filament suitable for extrusion-based additive manufacturing. Melt flow index of the filament and mechanical properties of the printed bars were tested. Preliminary results showed that the melt flow index increases significantly with cloisite and the modulus of polylactic acid/poly(butylene adipate-co-terephthalate) improved slightly. The notched impact strength of the blend increased with increasing content of cloisite, and it increased significantly after annealing, especially for blends without cloisite. Ke

Ligand-induced unfolding mechanism of an RNA G-quadruplex

The cationic porphyrin, TMPyP4, is a well-established DNA G-quadruplex (G4) binding ligand that can stabilize different topologies via multiple binding modes. However, TMPyP4 has completely opposite destabilizing and unwinding effect on RNA G4 structures. The structural mechanisms that mediate RNA G4 unfolding remains unknown. Here, we report on the TMPyP4-induced RNA G4 unfolding mechanism studied by well-tempered metadynamics (WT-MetaD) with supporting biophysical experiments. The simulations predict a two-state mechanism of TMPyP4 interaction via a groove-bound and a top-face bound conformation. The dynamics of TMPyP4 stacking on the top tetrad disrupts Hoogsteen H-bonds between guanine bases resulting in the consecutive TMPyP4 intercalation from top-to-bottom G-tetrads. The results reveal a striking correlation between computational and experimental approaches and validate WT-MetaD simulations as a powerful tool for studying RNA G4-ligand interactions

Resilience Mediates the Relationship Between Social Support and Quality of Life in Patients With Primary Glaucoma

Objective: Glaucoma is a serious disease causing blindness, which seriously affects the quality of life of patients. Previous studies have reported that both resilience and social support play important roles in enhancing the quality of life of patients with some diseases. The purpose of this study is to investigate if resilience mediates the relationship between social support and quality of life in patients with primary glaucoma.Methods: We conducted a cross-sectional study with 120 patients with primary glaucoma in China. The Connor-Davidson Resilience Scale was used to measure resilience, and social support was measured by the Perceived Social Support Scale. The Glaucoma Quality of Life-15 questionnaire was used to measure quality of life.Results: There were significant positive correlations between all dimensions and total scores on the resilience, social support, and quality of life scales (p < 0.01). Both resilience and social support could predict these patients' quality of life. A bootstrap test showed that resilience had a partial mediating effect on the relationship between social support and quality of life (p < 0.05).Conclusion: Resilience mediates the relationship between social support and quality of life in primary glaucoma patients. This finding suggests that increasing resilience and social support can improve the quality of life of primary glaucoma patients in clinical practice

Identification of New Agonists and Antagonists of the Insect Odorant Receptor Co-Receptor Subunit

BACKGROUND: Insects detect attractive and aversive chemicals using several families of chemosensory receptors, including the OR family of olfactory receptors, making these receptors appealing targets for the control of insects. Insect ORs are odorant-gated ion channels, comprised of at least one common subunit (the odorant receptor co-receptor subunit, Orco) and at least one variable odorant specificity subunit. Each of the many ORs of an insect species is activated or inhibited by an unique set of odorants that interact with the variable odorant specificity subunits, making the development of OR directed insect control agents complex and laborious. However, several N-,2-substituted triazolothioacetamide compounds (VUAA1, VU0450667 and VU0183254) were recently shown to act directly on the highly conserved Orco subunit, suggesting that broadly active compounds can be developed. We have explored the chemical space around the VUAA1 structure in order to identify new Orco ligands. PRINCIPAL FINDINGS: We screened ORs from several insect species, using heterologous expression in Xenopus oocytes and an electrophysiological assay, with a panel of 22 compounds structurally related to VUAA1. By varying the nitrogen position in the pyridine ring and altering the moieties decorating the phenyl ring, we identified two new agonists and a series of competitive antagonists. Screening smaller compounds, similar to portions of the VUAA1 structure, also yielded competitive antagonists. Importantly, we show that Orco antagonists inhibit odorant activation of ORs from several insect species. Detailed examination of one antagonist demonstrated inhibition to be through a non-competitive mechanism. CONCLUSIONS: A similar pattern of agonist and antagonist sensitivity displayed by Orco subunits from different species suggests a highly conserved binding site structure. The susceptibility to inhibition of odorant activation by Orco antagonism is conserved across disparate insect species, suggesing the ligand binding site on Orco as a promising target for the development of novel, broadly active insect repellants

Identification of Sare0718 As an Alanine-Activating Adenylation Domain in Marine Actinomycete Salinispora arenicola CNS-205

BACKGROUND: Amino acid adenylation domains (A domains) are critical enzymes that dictate the identity of the amino acid building blocks to be incorporated during nonribosomal peptide (NRP) biosynthesis. NRPs represent a large group of valuable natural products that are widely applied in medicine, agriculture, and biochemical research. Salinispora arenicola CNS-205 is a representative strain of the first discovered obligate marine actinomycete genus, whose genome harbors a large number of cryptic secondary metabolite gene clusters. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate cryptic NRP-related metabolites in S. arenicola CNS-205, we cloned and identified the putative gene sare0718 annotated "amino acid adenylation domain". Firstly, the general features and possible functions of sare0718 were predicted by bioinformatics analysis, which suggested that Sare0718 is a soluble protein with an AMP-binding domain contained in the sequence and its cognate substrate is L-Val. Then, a GST-tagged fusion protein was expressed and purified to further explore the exact adenylation activity of Sare0718 in vitro. By a newly mentioned nonradioactive malachite green colorimetric assay, we found that L-Ala but not L-Val is the actual activated amino acid substrate and the basic kinetic parameters of Sare0718 for it are K(m) = 0.1164±0.0159 (mM), V(max) = 3.1484±0.1278 (µM/min), k(cat) = 12.5936±0.5112 (min(-1)). CONCLUSIONS/SIGNIFICANCE: By revealing the biochemical role of sare0718 gene, we identified an alanine-activating adenylation domain in marine actinomycete Salinispora arenicola CNS-205, which would provide useful information for next isolation and function elucidation of the whole cryptic nonribosomal peptide synthetase (NRPS)-related gene cluster covering Sare0718. And meanwhile, this work also enriched the biochemical data of A domain substrate specificity in newly discovered marine actinomycete NRPS system, which bioinformatics prediction will largely depend on

An incomplete soft set and its application in MCDM problems with redundant and incomplete information

Multiple criteria decision making (MCDM) problems in practice may simultaneously contain both redundant and incomplete information and are difficult to solve. This paper proposes a new decision-making approach based on soft set theory to solve MCDM problems with redundant and incomplete information. Firstly, we give an incomplete soft set a precise definition. After that, the binary relationships of objects in an incomplete soft set are analyzed and some operations on it are provided. Next, some definitions regarding the incomplete soft decision system are also given. Based on that, an algorithm to solve MCDM problems with redundant and incomplete information based on an incomplete soft set is presented and illustrated with a numerical example. The results show that our newly developed method can be directly used on the original redundant and incomplete data set. There is no need to transform an incomplete information system into a complete one, which may lead to bad decision-making due to information loss or some unreliable assumptions about the data generating mechanism. To demonstrate its practical applications, the proposed method is applied to a problem of regional food safety evaluation in Chongqing, China