Short-Chain Fatty Acids Alleviate Vancomycin-Caused Humoral Immunity Attenuation in Rabies-Vaccinated Mice by Promoting the Generation of Plasma Cells via Akt-mTOR Pathway.

Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria (C. butyricum) and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4+ T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138+ PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. IMPORTANCE The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.

NinaB and BCO Collaboratively Participate in the ß-Carotene Catabolism in Crustaceans: A Case Study on Chinese Mitten Crab Eriocheir sinensis.

Carotenoid cleavage oxygenases can cleave carotenoids into a range of biologically important products. Carotenoid isomerooxygenase (NinaB) and ß, ß-carotene 15, 15'-monooxygenase (BCO1) are two important oxygenases. In order to understand the roles that both oxygenases exert in crustaceans, we first investigated NinaB-like (EsNinaBl) and BCO1-like (EsBCO1l) within the genome of Chinese mitten crab (Eriocheir sinensis). Their functions were then deciphered through an analysis of their expression patterns, an in vitro ß-carotene degradation assay, and RNA interference. The results showed that both EsNinaBl and EsBCO1l contain an RPE65 domain and exhibit high levels of expression in the hepatopancreas. During the molting stage, EsNinaBl exhibited significant upregulation in stage C, whereas EsBCO1l showed significantly higher expression levels at stage AB. Moreover, dietary supplementation with ß-carotene resulted in a notable increase in the expression of EsNinaBl and EsBCO1l in the hepatopancreas. Further functional assays showed that the EsNinaBl expressed in E. coli underwent significant changes in its color, from orange to light; in addition, its ß-carotene cleavage was higher than that of EsBCO1l. After the knockdown of EsNinaBl or EsBCO1l in juvenile E. sinensis, the expression levels of both genes were significantly decreased in the hepatopancreas, accompanied by a notable increase in the redness (a*) values. Furthermore, a significant increase in the ß-carotene content was observed in the hepatopancreas when EsNinaBl-mRNA was suppressed, which suggests that EsNinaBl plays an important role in carotenoid cleavage, specifically ß-carotene. In conclusion, our findings suggest that EsNinaBl and EsBCO1l may exhibit functional co-expression and play a crucial role in carotenoid cleavage in crabs.

EEG microstate temporal Dynamics Predict depressive symptoms in College Students.

Previous studies on resting-state electroencephalographic responses in patients with depressive disorders have identified electroencephalogram (EEG) parameters as potential biomarkers for the early detection and diagnosis of depressive disorders. However, these studies did not investigate the relationship between resting-state EEG microstates and the early detection of depressive symptoms in preclinical individuals. To explore the possible association between resting-state EEG microstate temporal dynamics and depressive symptoms among college students, EEG microstate analysis was performed on eyes-closed resting-state EEG data for approximately 5 min from 34 undergraduates with high intensity of depressive symptoms and 34 age- and sex-matched controls with low intensity of depressive symptoms. Five microstate classes (A-E) were identified to best explain the datasets of both groups. Compared to controls, the mean duration, occurrence, and coverage of microstate class B increased significantly, whereas the occurrence and coverage of microstate classes D and E decreased significantly in individuals with high intensity of depressive symptoms. Additionally, the presence of microstate class B was positively correlated with participants' Beck Depression Inventory-II (BDI-II) scores, and the presence of microstate classes D and E were negatively correlated with their BDI-II scores. Further, individuals with high intensity of depressive symptoms had higher transition probabilities of A→B, B→A, B→C, B→D, and C→B, with lower transition probabilities of A→D, A→E, D→A, D→E, E→A, E→C, and E→D than controls. These results highlight resting-state EEG microstate temporal dynamics as potential biomarkers for the early detection and timely treatment of depression in college students.

Self-Adhesive Hyaluronic Acid/Antimicrobial Peptide Composite Hydrogel with Antioxidant Capability and Photothermal Activity for Infected Wound Healing.

Bacterial infection can delay wound healing, causing wounds to deteriorate and even threaten the patient's life. Recently, although many composite hydrogels as wound dressing have been developed, it is still highly desired to construct photothermal hydrogels with antimicrobial and antioxidant properties to accelerate the infected wound healing. In this work, a hyaluronic acid (HA)-based composite hydrogel consisting of a dopamine-substituted antimicrobial peptide (DAP) and Iron (III) ions is developed, which exhibits photothermal-assisted promotion and acceleration of healing process of bacteria-infected wounds. DAP, serving as both antimicrobial agent and ROS-scavenger, forms Schiff's base bonds with aldehyde hyaluronic acid (AHA) and iron-catechol coordination bonds to reinforce the composite hydrogel. The presence of Fe3+ can also promote covalent polymerization of dopamine, which endows the hydrogel with photothermal capacity. The in vitro and in vivo experiments prove that the composite hydrogel can effectively accelerate the infected wound healing process, including antibacterial, accelerated collagen deposition, and re-epithelization. This study suggests that the multifunctional composite hydrogel possesses remarkable potential for bacteria-infected wound healing by combining inherent antimicrobial activity, antioxidant capability, and photothermal effect.

Cholesterol depletion inhibits rabies virus infection by restricting viral adsorption and fusion.

Rabies is an ancient zoonotic disease caused by the rabies virus (RABV), and a sharp increase in rabies cases and deaths were observed following the COVID-19 pandemic, indicating that it still poses a severe public health threat in most countries in the world. Cholesterol is one of the major lipid components in cells, and the exact role of cholesterol in RABV infection remains unclear. In this study, we initially observed that cellular cholesterol levels were significantly elevated in RABV infected cells, while cholesterol depletion by using methyl-ß-cyclodextrin (MßCD) could restrict RABV entry. We further found that decreasing the cholesterol level of the viral envelope could change the bullet-shaped morphology of RABV and dislodge the glycoproteins on its surface to affect RABV entry. Moreover, the depletion of cholesterol could decrease lysosomal cholesterol accumulation to inhibit RABV fusion. Finally, it was found that the depletion of cholesterol by MßCD was due to the increase of oxygen sterol production in RABV-infected cells and the enhancement of cholesterol efflux by activating liver X receptor alpha (LXRα). Together, our study reveals a novel role of cholesterol in RABV infection, providing new insight into explore of effective therapeutics for rabies.