Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy.

The complement system is a complex network of proteins that plays a crucial role in the innate immune response. One important component of this system is the C5a-C5aR1 complex, which is critical in the recruitment and activation of immune cells. In-depth investigation of the activation mechanism as well as biased signaling of the C5a-C5aR1 system will facilitate the elucidation of C5a-mediated pathophysiology. In this study, we determined the structure of C5a-C5aR1-Gi complex at a high resolution of 3 Å using cryo-electron microscopy (Cryo-EM). Our results revealed the binding site of C5a, which consists of a polar recognition region on the extracellular side and an amphipathic pocket within the transmembrane domain. Furthermore, we found that C5a binding induces conformational changes of C5aR1, which subsequently leads to the activation of G protein signaling pathways. Notably, a key residue (M265) located on transmembrane helix 6 (TM6) was identified to play a crucial role in regulating the recruitment of ß-arrestin driven by C5a. This study provides more information about the structure and function of the human C5a-C5aR1 complex, which is essential for the proper functioning of the complement system. The findings of this study can also provide a foundation for the design of new pharmaceuticals targeting this receptor with bias or specificity.

Loss of the ceramide synthase HYL-2 from Caenorhabditis elegans impairs stress responses and alters sphingolipid composition.

Sphingolipids, essential membrane components and signaling molecules in cells, have ceramides at the core of their metabolic pathways. Initially termed as "longevity assurance genes", the encoding genes of ceramide synthases are closely associated with individual aging and stress responses, although the mechanisms remain unclear. This study aims to explore the alterations and underlying mechanisms of three ceramide synthases, HYL-1, HYL-2, and LAGR-1, in the aging and stress responses of Caenorhabditis elegans. Our results showed the knockdown of HYL-1 extends the lifespan and enhance stress resistance in worms, whereas the loss of HYL-2 function significantly impairs tolerances to heat, oxidation, and ultraviolet stress. Stress intolerance induced by HYL-2 deficiency may result from intracellular mitochondrial dysfunction, accumulation of reactive oxygen species, and abnormal nuclear translocation of DAF-16 under stress conditions. Loss of HYL-2 led to a significant reduction of predominant ceramides (d17:1/C20∼C23) as well as corresponding complex sphingolipids. Furthermore, the N-acyl chain length composition of sphingolipids underwent dramatic modifications, characterized by a decrease in C22 sphingolipids and an increase in C24 sphingolipids. Extra d18:1-ceramides resulted in diminished stress resilience in wild-type worms, while supplementation of d18:1/C16 ceramide to HYL-2-deficient worms marginally improved stress tolerance to heat and oxidation. These findings indicate the importance of appropriate ceramide content and composition in maintaining subcellular homeostasis and nuclear-cytoplasmic signal transduction during healthy aging and stress responses.

Donate for your Secrets: Relationship between Secrecy, Guilt and Donation Behavior.

Previous research has well documented the negative sides of secrecy, ignoring its potential constructive aspects. Based on the concept of compensatory behavior, this study conducted two experiments with 532 adults to explore the mediating role of felt guilt between secrecy and donation, and the moderating role of moral identity. Study 1 (N = 272) showed that felt guilt mediated the relationship between secrecy and donation behaviors. Study 2 (N = 260) validated the mediation effect of Study 1 and further indicated that the mediated path was stronger for participants with higher moral identity. Specifically, participants with higher moral identity felt more guilty and donated more after secrecy than those with lower moral identity. The results of this study not only expand the constructive consequences of secrecy but also add more ways to appeal for donations.

Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis.

BACKGROUND: Euglena is a new super health food resource that is rich in the natural polysaccharide paramylon, a linear ß-1,3-glucan with various biological activities including activity on the immune system in different cell lines and animals. Despite these reports, the immune regulation mechanism of paramylon is still unclear. RESULTS: We investigate the signaling pathways paramylon impacts in immune macrophages. In RAW264.7 macrophages, sonicated and alkalized paramylon oligomers up-regulated inducible nitric oxide synthase (iNOS) and increased secretion of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a concentration-dependent manner. In addition, paramylon activated the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and inhibiting these pathways attenuated the paramylon-induced secretion of the above immune-mediators. CONCLUSIONS: These results demonstrate that Euglena gracilis paramylon modulates the immune system via activation of the NF-κB and MAPK signaling pathways and thus has potential therapeutic benefits.

The inhibitory activity of alginate against allergic reactions in an ovalbumin-induced mouse model.

Marine seaweed polysaccharides have been considered as a potential resource for antiallergic therapy. Alginate is an acidic linear polysaccharide and soluble dietary fiber that was extracted from brown algae, Laminaria japonica. The molecular weight of alginate was 108 kDa, and its water solution exhibited non-Newtonian characteristics, including viscoelasticity and shear-thinning behavior. The ability of alginate to inhibit allergic reactions was investigated in ovalbumin (OVA)-induced BALB/c mice, which have been widely used as a mouse model of egg allergy. The results showed that alginate could effectively attenuate the occurrence of allergic reactions, including improving the integrity of the intestinal epithelial villi and inhibition of mast cell degranulation in the jejunum, in OVA-induced mice. Moreover, after treatment with alginate, the levels of IgE, histamine and IL-4 in OVA-induced mice were remarkably decreased, and the levels of IFN-γ were markedly increased. In addition, the number of Treg cells in spleen tissues in OVA-induced mice was increased by alginate, and the OVA-induced differentiation of Th0 cells into Th2 cells was significantly inhibited. These results demonstrate that alginate possesses potential antiallergic activities in a mouse model of egg allergy, which might provide important evidence that alginate, extracted from Laminaria japonica, can be developed into a novel functional food for inhibiting egg allergy.

Immune Activation of RAW264.7 Macrophages by Low Molecular Weight Fucoidan Extracted from New Zealand Undaria pinnatifida.

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has been shown to possess various bioactivities. In particular, low molecular weight fucoidan (LMWF) has been shown to have better bioactivities. In this study, a LMWF (<10 kDa) was extracted from New Zealand Undaria pinnatifida and investigated for its immune modulation effects. LMWF at a concentration range from 1 to 50 µg/mL exerted an effective immune activation in RAW264.7 macrophages. LMWF treatment promoted significant NO release, iNOS expression, and TNF-α and IL-6 secretion in a concentration-dependent manner. It also significantly stimulated the activation of NF-κB and MAPK signaling pathways, and specific inhibitors of NF-κB and MAPK pathways diminished the stimulation, confirming the activation pathways. These results indicate that LMWF possesses potential health benefits through immune-stimulation, which may lead to future pharmaceutical development.

Iron oxide/lignin-based hollow carbon nanofibers nanocomposite as an application electrode materials for supercapacitors.

Iron oxide particle-decorated, hollow, carbon nanofibers (HCNFs), with poly(styrene-co-acrylonitrile) solution as the core and acetic acid lignin as the shell, were manufactured using a coaxial electrospinning technique, using iron(III) acetylacetonate as the iron oxide-precursor additive in the shell. The fabricated HCNFs exhibited a high specific capacitance of 121 F·g-1 at 0.5 A·g-1, which was 2.18-fold that of solid electrospun nanofibers under the same conditions. The samples also possessed a superior cycling life, with a 90% retention rate after 1000 cycles in 1 M sodium sulfite. In this system, HCNFs exhibited high surface areas, as the result of hollow structures and producing capacitance improvement, while iron oxide particles enhanced electrochemical properties via reversible redox reactions. The attractive performances exhibited by these supercapacitors yielded them potentially promising candidates for future energy storage systems.

High-value utilization of eucalyptus kraft lignin: Preparation and characterization as efficient dye dispersant.

The dark color of industrial lignin is the main obstacle for their high value-added use in areas such as dyestuff dispersants. A kind of light-colored lignosulfonate with favorable dispersibility and remarkable stain resistance is prepared using fractionated eucalyptus kraft lignin. The fractionated lignins named as D (insoluble part) and X (soluble part) and sulfonated lignin fractions named as SD and SX are characterized by FTIR spectroscopy, 1H NMR spectroscopy, GPC and brightness test. The results reveal that fraction X presents a lower molecular weight but a higher hydroxyl content than that of fraction D, which lead to the differences on the SO3H content, dispersibility and color performance of SD and SX. The sulfonated fractions perform a similar molecular weight to that of unsulfonated lignins and show light color due to the phenolic hydroxyl blocking of 1,4-BS (1,4-butane sultone) and the postprocessing of sodium borohydride. The SX that performs the best of all exhibits obvious decrease on phenolic hydroxyl groups and increase on brightness value which is improved by 85.8% compared with control sample. The SX reaches the highest level (grade 5) in the dispersibility test and presents remarkable stain resistance on different textiles, especially on the dacron and cotton.

Fractal-like tree networks increasing the permeability.

The effective permeability of composites embedded with self-similar fractal-like tree networks is studied. The effective permeability tensor of the composites is derived and is found to be related to microstructures of the networks. The present results show that the larger the ratio of successive branching channel diameters, the higher the effective permeability; the higher the relative surface porosity of the tree networks and matrix, the higher the effective permeability; the denser the tree networks, the lower the effective permeability; the longer the branches, the lower the effective permeability. It is found that the dimensionless effective permeability of composites scales as the diameter exponent by K+(e,y) approximately beta alpham, with alpha approximately 4. It is also found that when m>1 and nbeta4/gamma<1, the effective permeability K+(e,y) scales as the iteration m, ln K+(e,y)/m approximately ln (nbeta4/gamma). The fractal-like tree networks can significantly increase the effective permeability of the composites compared to the traditional parallel nets under properly chosen structural parameters.

Fractal-like tree networks reducing the thermal conductivity.

The effective thermal conductivity of composites with embedded self-similar H-shaped fractal-like tree networks is studied. It is found that the effective thermal conductivity of the composites with these networks is related to the structures of the networks and the ratio of the component thermal conductivities: the longer the branches, the lower the thermal conductivity; the smaller the ratio (beta) of successive branch diameters, the lower the thermal conductivity; the denser the network, the lower the thermal conductivity. It is also found that the thermal conductivity of the H-shaped fractal-like tree networks does not obey Murray's law. The present results show that a network embedded in a composite plays an important role, and the thermal conductivity of the network itself may be less than that of the original material by several orders of magnitude. Fractal-like tree networks can significantly reduce the thermal conductivity compared to an equivalent single cylinder.