Early evolution of the ecdysozoan body plan.

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e. elongated and tubular) of their ancestral body plan. We describe here Beretella spinosa gen. et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament. Beretella spinosa gen. et sp. nov has no equivalent among animals, except Saccorhytus coronarius, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.

Controlling the speed of antigens transport in dendritic cells improves humoral and cellular immunity for vaccine.

Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.

A General Strategy toward Self-assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

The effect of lentinan on dexamethasone-induced immunosuppression in mice.

The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.

Preparation and characterization of pickering emulsion stabilized by lovastatin nanoparticles for vaccine adjuvants.

While research on mevalonate inhibitors as vaccine adjuvants has made great progress to enhance the effectiveness of the vaccine, co delivery of lovastatin and antigens (OVA) remains an enormous challenge. Here, we encapsulated lovastatin into PLGA nanoparticles. PLGA loading lovastatin was further emulsified with squalene to prepare Pickering emulsion. The emulsification conditions of Pickering emulsion were optimized, and the optimal preparation conditions were obtained. After loading lovastatin and OVA, the size and zeta potential of LS-PPAS/OVA was 1043.33 nm and -22.07 mv, the adsorption rate of OVA was 63.34 %. The adsorbing of LS-PLGA nanoparticles on the surface of squalene in Pickering emulsions was demonstrated by Fluorescent confocal microscopy. After immunization, LS-PPAS enhanced the activation of dendritic cells in lymph nodes, further study found LS-PPAS not only elicited elevated levels of OVA-specific IgG and its subtypes, but also promoted the secretion of TNF-α, IFN-γ, and IL-6 in serum as a marker of cellular immunity. Importantly, LS-PPAS showed sufficient security through monitoring levels of biochemical parameters in serum and pathological observation of organ following vaccinations. LS-PPAS may act as a promising vaccine carrier to produce strong humoral and cellular immunity with acceptable safety.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity.

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

Lentinan-functionalized graphene oxide hydrogel as a sustained antigen delivery system for vaccines.

Hydrogel has been proven to have the ability to deliver antigens continuously to achieve slow vaccine delivery, which makes it a promising candidate for an adjuvant delivery platform. Meanwhile, graphene oxide (GO) has garnered significant attention due to its good biosafety, excellent surface area and easy modification. However, GO exists as weak colloidal particles and poses challenges in self-assembling into a hydrogel structure. Here, we propose an innovative strategy involving self-assembling lentinan-functionalized graphene oxide hydrogel ((LNT-GO Gel) by simply mixing lentinan (LNT)-functionalized GO with polyethylene imide (PEI), which can simultaneously encapsulate antigens, achieve long-lasting release of antigens and generate excellent adjuvant activity. The results indicated that the LNT-GO Gel can control the release of OVA at the injection site and confer targeted delivering capacity to lymph nodes. And the date demonstrates that LNT-GO Gel displays favorable safety and biodegradability in vivo. Moreover, LNT-GO Gel can enhance the activation and maturation of dendritic cells (DCs) in lymph node, induce stronger OVA-specific antibody response, and promote spleen T lymphocyte differentiation, which underscores that LNT-GO Gel has ability to generate stronger antigen-specific humoral and cellular immune responses. Collectively, these results demonstrate the adjuvant potential of the lentinan-functionalized graphene oxide hydrogel (LNT-GO Gel) for subunit vaccine.

Aldanella attleborensis (Mollusca) from Cambrian Stage 2 of the Three Gorges Area and Its Stratigraphic Implications.

Some small shelly fossils are important index fossils for global stratigraphic subdivisions and correlations of the Cambrian Terreneuvian. The first appearance datum (FAD) of the cosmopolitan mollusk Aldanella attleborensis has been suggested as one of the potential markers for defining the base of Cambrian Stage 2. Aldanella fossils were uncommon in South China, and if occurring, were often described as Aldanella yanjiaheensis, A. attleborensis, or indeterminate species in the literature, while A. yanjiaheensis was often taken as a junior synonym of A. attleborensis. Nevertheless, a detailed taxonomic revision of A. yanjiaheensis based on material from its type locality awaits to be made. In this study, we systematically re-evaluated A. yanjiaheensis based on the numerous specimens collected from the base of Member 5 of the Yanjiahe Formation in the Three Gorges area, western Hubei Province of South China. Detailed taxonomic comparison further substantiates that A. yanjiaheensis is a junior synonym of A. attleborensis, signifying its strong potential for a global correlation across paleocontinents. Morphological parameter analyses indicate that the length and width of shell tube of A. attleborensis shows allometric growth. The nearly cosmopolitan distribution and characteristic morphology of A. attleborensis indicate that it can play a significant role in the subdivision and correlation of Cambrian Stage 2. The co-occurrence of A. attleborensis and Watsonella crosbyi from the base of Member 5 of the Yanjiahe Formation corroborates that Member 5 belongs to Cambrian Stage 2.

Continued evolution of the Eurasian avian-like H1N1 swine influenza viruses in China.

Animal influenza viruses continue to pose a threat to human public health. The Eurasian avian-like H1N1 (EA H1N1) viruses are widespread in pigs throughout Europe and China and have caused human infections in several countries, indicating their pandemic potential. To carefully monitor the evolution of the EA H1N1 viruses in nature, we collected nasal swabs from 103,110 pigs in 22 provinces in China between October 2013 and December 2019, and isolated 855 EA H1N1 viruses. Genomic analysis of 319 representative viruses revealed that these EA H1N1 viruses formed eight different genotypes through reassortment with viruses of other lineages circulating in humans and pigs, and two of these genotypes (G4 and G5) were widely distributed in pigs. Animal studies indicated that some strains have become highly pathogenic in mice and highly transmissible in ferrets via respiratory droplets. Moreover, two-thirds of the EA H1N1 viruses reacted poorly with ferret serum antibodies induced by the currently used H1N1 human influenza vaccine, suggesting that existing immunity may not prevent the transmission of the EA H1N1 viruses in humans. Our study reveals the evolution and pandemic potential of EA H1N1 viruses and provides important insights for future pandemic preparedness.

Ocruranus-Eohalobia Sclerites from the Cambrian Stage 2 Yanjiahe Formation in South China: Scleritome Reconstruction and Zoological Affinity.

The isolated sclerites of the Ocruranus and Eohalobia group are abundant among the early Cambrian small shelly fossil assemblages, which were recently assigned to the same scleritome as an early member of the polyplacophoran (chiton) stem lineage. However, the scleritome reconstruction and zoological affinities of these sclerites are still controversial due to the lack of exceptionally preserved articulated specimens with in-situ sclerites. Herein, we report new specimens of Ocruranus and Eohalobia sclerites from Member 5 of the Yanjiahe Formation, which provide new insights into the reconstruction of the original scleritome. The Eohalobia sclerites from the Yanjiahe Formation have an extended and upfolded proximal field with dense wrinkles, which seems to be a weakly mineralized structure and acted as a joint with another sclerite, Ocruranus. Comparing the butterfly-shaped proximal field on a unique sclerite of Eohalobia with the sub-apical field on Ocruranus sclerites suggests that the original scleritome of this group may consist of only two types of sclerites: the Ocruranus-type and the Eohalobia-type. The polygonal structure on the internal mold of Eohalobia sclerites is interpreted herein as the muscle attachment zone; their distribution corresponds well with that of the modern chitons, which provides strong evidence to support the close relationship between the Ocruranus-Eohalobia group and the Polyplacophora.

Pickering emulsion stabilized by Chinese Yam polysaccharides PLGA for enhanced humoral and cellular immune responses.

As an important ingredient of Chinese yam, Chinese yam polysaccharides have received wide attention for their remarkable adjuvant activity. Pickering emulsion is an attractive platform for the delivery of vaccines. Our previous study has demonstrated that the Chinese yam polysaccharides PLGA-stabilized Pickering emulsion (CYP-PPAS) is a potentially safe and efficient adjuvant to improve the immune response. In this work, we further investigate the adjuvant activity of CYP-PPAS on cellular immunity. In vitro, the CYP-PPAS increased antigen uptake efficiency by DCs. In vivo, CYP-PPAS triggered the recruitment of DCs and macrophages and subsequently facilitated DCs maturation and antigen migration to lymph nodes. Furthermore, CYP-PPAS induced a robust humoral response and Th1/Th2 immune response, enhanced the activation of CD4+ and CD8+ T lymphocyte subpopulations, and also promoted the activation of cytotoxic T lymphocyte response. As a result, the CYP-PPAS serves as a promising vaccine delivery system to induce robust humoral and cellular immunities against diseases.

Isolation, purification and characterization of Pueraria lobata polysaccharide and its effects on intestinal function in cyclophosphamide-treated mice.

This study investigated the structure of acidic Pueraria lobata polysaccharide (a-PLP) and its bioactive effects on intestinal function in cyclophosphamide (CY)-treated mice. The structure of a-PLP was preliminarily analyzed, and the results showed that it is composed of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid in a molar proportion of 2.54:16.52: 6.14: 16.60: 4.05: 4.75: 0.48: 47.44: 1.47 with a weight average molecular weight of 22.675 kDa. In addition, the methylation analysis suggested that 4-Gal(p)-UA may be the main backbone of a-PLP. Furthermore, a-PLP (1.2 g/kg, 0.8 g/kg, and 0.4 g/kg) was administered orally for the treatment of CY-treated mice. The results showed that a-PLP could remarkably relieved weight loss and intestinal villous atrophy in CY-treated mice. Meanwhile, the secretion levels of sIgA, ß-defensin, cytokines, Mucin-2, and tight junction proteins increased significantly. Moreover, the ratio of T (CD4+ and CD8+) cells in the Peyer's patches and mesenteric lymph nodes also increased remarkably, along with the number of goblet cells. Furthermore, a-PLP decreased the levels of diamino oxidase and malondialdehyde, but up-regulated the activity of superoxide dismutase. In summary, a-PLP exhibited great benefits by attenuating CY side effects, opening a potential avenue to effectively treat cancer and reduce the suffering of chemotherapy patients.