The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P < 0.05), suggesting the weaning period may be an effective window for A. muciniphila intervention. Following that, 48 crossbred weaned pigs at 28 d old were randomly assigned to five groups: control (CON), high/low live A. muciniphila (HA/LA), and high/low heat-killed A. muciniphila (HIA/LIA). From 1 to 28 d old, the CON group received gastric infusion of anaerobic sterile saline every other day; the HA and LA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL live A. muciniphila, respectively; and the HIA and LIA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL heat-killed A. muciniphila, respectively. At d 29, pigs in the CON group were randomly and equally divided into two groups, one of which was named the enterotoxigenic Escherichia coli (ETEC) group, and all groups except CON received a 5-d ETEC challenge. The supplementation of A. muciniphila numerically reduced the diarrhea rate of weaned pigs compared to the pigs that only received the ETEC challenge (P = 0.57), but the LIA group had a higher diarrhea rate than the CON group (P < 0.05). Consistent with this, the supplementation of A. muciniphila improved the small intestinal morphology and structure, proportion of CD4+ T lymphocytes in the blood, as well as the expression of genes related to intestinal barrier and antioxidant indices of pigs with ETEC challenge, especially for the LA group (P < 0.05). Meanwhile, A. muciniphila supplementation reduced the expression of ETEC virulence factor genes in the ileum and colon of pigs challenged by ETEC (P < 0.05). Therefore, A. muciniphila may protect the intestinal health of weaned piglets from damage caused by ETEC infection, but the effect may vary depending on the concentration and activity of A. muciniphila.
Recently, the near-infrared-II (NIR-II, 1000–1350 nm) region has been extensively applied in deep-tissue photothermal therapy (PTT) on account of it having stronger tissue penetration and a higher maximum permissible exposure (MPE) than the near-infrared-I (NIR-I, 650–950 nm) region. In this study, we developed a rapid and convenient in situ polymerization strategy to fabricate polypyrrole nanosheets (PPy NSs) within a few minutes using manganese dioxide nanosheets (MnO2 NSs) as both the oxidant and the self-sacrificed template. The fabricated PPy NSs exhibited excellent NIR-II absorption, which conferred its high photothermal conversion efficiency (66.01%) at 1064 nm and its photoacoustic (PA) imaging capability. Both in vivo and in vitro studies have shown that that PPy NSs possess good biological safety and excellent PTT efficacy and PA imaging performances. Thus, the as-synthesized PPy NSs could effectively achieve PA imaging-guided photothermal tumor ablation under 1064 nm excitation. Our work provides a novel and promising method for the rapid preparation of PPy NSs without the addition of exogenous oxidants and subsequent template removal, which could be regarded as potential photothermal agents (PTAs) to integrate the diagnosis and treatment of cancer.
Affinity membranes have the potential to enhance the specific adsorption of toxins, however, they suffer from insufficient hemocompatibility and low therapeutic efficiency during blood detoxification therapy. Herein, we combine an affinity membrane with a bioreactor to develop a blood purification membrane with affinity adsorption detoxification and cell detoxification functions. To fabricate the membrane, a polyethersulfone (iPES) membrane with a macroporous support layer was prepared by a phase inversion technique and modified with polydopamine (PDA). The iPES/PDA composite membrane exhibited excellent biocompatibility and blood compatibility, as well as controllable permeability. Lysine (Lys) and hepatocytes (C3A cells), which were selected as the affinity ligand for bilirubin adsorption and detoxification cells, respectively, were immobilized on the iPES/PDA composite membrane via the active group and adhesiveness of PDA coating on the membrane. The fabricated C3A cells-inoculated iPES/PDA/Lys membrane not only achieved high cell activity and function of the inoculated cells but also significantly improved the toxin clearance efficiency.