Rationale: Immune checkpoint (ICP) blockade therapy combined with chemotherapy is a promising treatment strategy for tumors. Chemotherapeutic agents usually function inside the tumor cells, while ICP inhibitors are efficacious out of the tumor cells. It is desirable to effectively co-deliver an ICP inhibitor and a chemotherapy agent to different sites of a tumor. We have designed an effective drug delivery system to accomplish both objectives.

Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.

Captive breeding has been explored in Chinese sturgeon (Acipenser sinensis) for species protection. However, gonad development from stage II to IV of cultured female broodstocks is a handicap. This study aimed to explore the physiological and metabolic changes during the ovary development from stage II to IV of female Chinese sturgeon and the related energy regulatory mechanism, which may be helpful to address the developmental obstacle. The results showed that the oocyte volume increased and the muscle lipid content decreased with the ovary development. Ovarian RNA levels of most genes related to lipid and amino acid metabolism were higher in stage II and III than in stage IV. Serum contents of differential metabolites in arginine, cysteine, methionine, purine, tyrosine, lysine, valine, leucine and isoleucine metabolism pathways peaked at stage III, while the contents of sarcosine, alanine and histidine, as well as most oxylipins derived from fatty acids peaked at stage IV. These results indicated the more active amino acids, lipid metabolism, and energy dynamics of fish body in response to the high energy input of ovary developing from stage II to III, and the importance of alanine, histidine, taurine, folate and oxylipins for fish with ovary at stage IV.