Developing oral nanomedicines that suppress intestinal inflammation while modulating gut microbiota and brain interactions is essential for effectively treating inflammatory bowel disease. Here, we report an oral polyphenol-armored nanomedicine based on tumor necrosis factor–α (TNF-α)–small interfering RNA and gallic acid–mediated graphene quantum dot (GAGQD)–encapsulated bovine serum albumin nanoparticle, with a chitosan and tannin acid (CHI/TA) multilayer. Referred to “armor,” the CHI/TA multilayer resists the harsh environment of the gastrointestinal tract and adheres to inflamed colon sites in a targeted manner. TA provides antioxidative stress and prebiotic activities that modulate the diverse gut microbiota. Moreover, GAGQD protected TNF-α–siRNA delivery. Unexpectedly, the armored nanomedicine suppressed hyperactive immune responses and modulated bacterial gut microbiota homeostasis in a mouse model of acute colitis. Notably, the armored nanomedicine alleviated anxiety- and depression-like behaviors and cognitive impairment in mice with colitis. This armor strategy sheds light on the effect of oral nanomedicines on bacterial gut microbiome-brain interactions.

The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.

Neurological disorders after severe acute pneumonia have been attacked much attention in recent years. However, the underline mechanisms remain not very clear. Here we show that these neurological syndromes after severe acute pneumonia are partly attributed to the translocation of bacteria from the lung to the brain during acute pneumonia. We detected an emerging and increased bacteria in the brain tissue of mice with lipopolysaccharide-induced experimental severe pneumonia. Interestingly, using 16S rDNA amplification sequencing, similarities were found between the brain's flora species and those of the lungs, indicating the bacteria in the brain may come from the lung. We also observed the impairment of the lung-blood barrier and brain-blood barrier, simultaneously, allowing lung bacteria invade the brain during pneumonia. An elevated microglia and astrocytes activation markers signature though bacterial infection-related pathways are observed by single-cell RNA sequencing, indicating a bacteria-induced disruption of brain homeostasis. Rapamycin delivered by platelet-derived extracellular vesicles provides an effective strategy to rescue the brain microenvironment and neurological disorders. Collectively, we identify lung bacteria that play a role in altering brain homeostasis, which provides new insight into the mechanism of neurological syndromes after severe pneumonia.

Severe pneumonia may induce sequelae and accelerated aging process even after the person has recovered. However, the underline mechanism is not very clear. More research is needed to fully understand the longterm effects of severe pneumonia. In this study, we found that mice recovered from severe pneumonia showed lung immunosenescence, which was characterized by a bias naive-memory balance of T lymphocytes in the lung. The reduction of naïve T cells is associated with the diminished immune response to cancer or external new antigens, which is one of the key changes that occurs with age. Our results also indicate the link between severe pneumonia and aging process, which is mediated by the disrupted T cells homeostasis in the lungs after pneumonia. AGING MATERIALS AND METHODS MaterialsThe following materials were used in this study. Table 1. Reagent used in this study. REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies FITC anti-mouse CD3 Biolegend Cat # 100204 APC anti-mouse CD4 Biolegend Cat # 100412 PE anti-mouse CD8a Biolegend Cat # 100708 PE anti-mouse CD45 Biolegend Cat # 103106 PE anti-mouse CD44 Biolegend Cat # 103008 APC anti-mouse CD62L Biolegend Cat # 104412 PE anti-mouse FOXP3 Biolegend Cat # 126403 APC anti-mouse IL-4 Biolegend Cat # 504105 PE anti-mouse/rat/human MCP-1 Biolegend Cat # 505903 Anti-CEA Servicebio Cat # GB112292