A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells.

BACKGROUND: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. OBJECTIVES: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. METHODS: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. RESULTS: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. CONCLUSIONS: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.

Photothermal-responsive lignin-based polyurethane with mechanically robust, fast self-healing, solid-state plasticity and shape-memory performance.

In light of the depletion of petrochemical resources and increase in environmental pollution, there has been a significant focus on utilizing natural biomass, specifically lignin, to develop sustainable and functional materials. This research presents the development of a lignin-based polyurethane (DLPU) with photothermal-responsiveness by incorporating lignin and oxime-carbamate bonds into polyurethane network. The abundant hydrogen bonds between lignin and the polyurethane matrix, along with its cross-linked structure, contribute to DLPU's excellent mechanical strength (30.2 MPa) and toughness (118.7 MJ·m-3). Moreover, the excellent photothermal conversion ability of DLPU (54.4 %) activates dynamic reversible behavior of oxime-carbamate bonds and hydrogen bonds, thereby endowing DLPU with exceptional self-healing performance. After 15 min of near-infrared irradiation, DLPU achieves self-healing efficiencies of 96.0 % for tensile strength and 96.3 % for elongation at break. Additionally, DLPU exhibits photocontrolled solid-state plasticity as well as an excellent phototriggered shape-memory effect (70 s), with shape fixity and recovery ratios reaching 98.8 % and 95.3 %, respectively. By exploiting the spatial controllability and photothermal-responsiveness of DLPU, we demonstrate multi-dimensional responsive materials with self-healing and shape-shifting properties. This work not only promotes the development of multi-functional polyurethanes but also provides a pathway for the high-value utilization of lignin.

Construction and mechanism study of lignin-based polyurethane with high strength and high self-healing properties.

Lignin is a natural polymer with abundant functional groups with great application prospects in lignin-based polyurethane elastomers with self-healing abilities. In this study, a lignin self-healing polyurethane (PUDA-L) was specially designed using lignin as the raw material of polyurethane, combining lignin with Diels-Alder (DA) bond and hydrogen bonds. The experimental results showed that PUDA-L was prepared with good thermal stability, fatigue resistance, shape memory effect, excellent mechanical strength, and self-healing ability by partially replacing the crosslinking agents with bio-based lignin and hydroxylated modified lignin to increase the hydroxyl content. Polyurethane has a tensile strength of up to 29 MPa and an elongation at break of up to 500 %. The excellent self-healing ability of PUDA-L originates from the internal DA bonds and cross-linked hydrogen bonds. After the dumbbell sample was fused and heated at 130 °C for 4 h, the elastomer could be completely healed, the tensile strength was restored to 29 MPa, and the self-healing efficiency was up to 100 %. The developed PUDA-L elastomer has promising applications in sensors and smart skins.

Functional and structural diversification of incomplete phosphotransferase system in cellulose-degrading clostridia.

Carbohydrate utilization is critical to microbial survival. The phosphotransferase system (PTS) is a well-documented microbial system with a prominent role in carbohydrate metabolism, which can transport carbohydrates through forming a phosphorylation cascade and regulate metabolism by protein phosphorylation or interactions in model strains. However, those PTS-mediated regulated mechanisms have been underexplored in non-model prokaryotes. Here, we performed massive genome mining for PTS components in nearly 15,000 prokaryotic genomes from 4,293 species and revealed a high prevalence of incomplete PTSs in prokaryotes with no association to microbial phylogeny. Among these incomplete PTS carriers, a group of lignocellulose degrading clostridia was identified to have lost PTS sugar transporters and carry a substitution of the conserved histidine residue in the core PTS component, HPr (histidine-phosphorylatable phosphocarrier). Ruminiclostridium cellulolyticum was then selected as a representative to interrogate the function of incomplete PTS components in carbohydrate metabolism. Inactivation of the HPr homolog reduced rather than increased carbohydrate utilization as previously indicated. In addition to regulating distinct transcriptional profiles, PTS associated CcpA (Catabolite Control Protein A) homologs diverged from previously described CcpA with varied metabolic relevance and distinct DNA binding motifs. Furthermore, the DNA binding of CcpA homologs is independent of HPr homolog, which is determined by structural changes at the interface of CcpA homologs, rather than in HPr homolog. These data concordantly support functional and structural diversification of PTS components in metabolic regulation and bring novel understanding of regulatory mechanisms of incomplete PTSs in cellulose-degrading clostridia.

Molecular cloning, characterization and expression pattern of androgen receptor in Spinibarbus denticulatus.

Androgens play key roles in sex differentiation, gonadal maturation and reproductive behaviors and their actions are generally mediated through androgen receptor (AR). In the present study, isolation, sequencing and characterization of cDNA encoding AR and its temporal and spatial expression profiles in both sexes of Spinibarbus denticulate were carried out. Androgen receptor of Spinibarbus denticulate (sdAR) was 3172bp in length and encoded a 95.4kDa protein of 865 amino acids. Phylogenetic analysis and multiple amino acids sequence alignment indicated the close relationship and high score similarity of sdAR with ARs of other cyprinid species. A single transcript of approximate 3.2kb was identified in testis, liver and brain. RT-PCR assay characterized that sdAR mRNA was broadly distributed in both central nervous system (CNS) and most of peripheral tissues in male fish, while was confined to olfactory, telencephalon and hypothalamus of CNS and peripheral tissues including liver, spleen, head kidney, heart, and red muscle in females. During the embryonic development, sdAR mRNA was firstly detected at 16-cells stage and mid blastula stage with very weak signal. Little or no signal was detected in mid gastrula and neurula stages. The expression was occurred in the following developmental phases as well as in larvae of 4 days post hatching. During gonadal recrudescence process, liver of both sexes and testis were the most AR mRNA abundant tissues. In male fish, abundance of sdAR mRNA significantly varied in pituitary at fully recrudesced stage and brain at late recrudescing phase, respectively. No significant variation was found throughout the ovary recrudesce in each tissue checked. Our present work provided preliminary evidences that AR mediated androgen action on reproduction and development in both sexes of S. denticulate.

Discovery of four estrogen receptors and their expression profiles during testis recrudescence in male Spinibarbus denticulatus.

Estrogen plays an important role in male reproduction. Most of the actions are mediated by estrogen receptor (ER). To investigate the profile of estrogen affecting male fertility, we firstly cloned four ERs from the male Spinibarbus denticulatus, a local economically important cyprinid fish in China. Phylogenetic tree analysis ranked the four sdERs as two distinct groups of ERalpha and beta, which could be further divided into duplicated isoforms 1 and 2, respectively. High score identities were shared between each of the duplicated isoforms. All of the four sdERs distributed in central nervous system of male fish with a quite broad spectrum. However, distribution diversity became evident between sdERalpha and sdERbeta subtypes in the peripheral tissues. Both of the two isoforms of ERbeta were detected in all seven tissues examined, while expression of sdERalpha1 was mainly limited to liver, kidney, testis and intestine and sdERalpha2 was confined to liver, heart, kidney, testis and gill. During the testis recrudescing stages, serum concentration of luteinizing hormone (LH), testosterone (T) and estradiol-17beta (E(2)) were increasing. T and LH levels in the circulation were high until the later fully recrudesced phase, while serum E(2) level was low all the time. Quantitative real-time RT-PCR analysis determined the most abundance of sdERs in pituitary where the two sdERalpha isoforms positively expressed with testis development, while sdERbeta isoforms expressed with a reverse pattern. sdERalpha1 and sdERbeta1 were the primary forms in testis. sdERalpha1 gradually increased during the recrudescence process while sdERbeta1 firstly decreased during the recrudescing stage and then positively expressed in fully recrudesced stage. Little or no signal was detected in brain. The present work provided evidence of four sdERs in male reproductive system and suggested an important role of sdERalpha1 during testis recrudescence. Pituitary contained duplicates forms of sdERalpha which may play a role in the feedback effects of estrogen on LH secretion.