No abstract

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

a b s t r a c tOrthorhombic hydrated tungsten trioxide (3WO 3 ·H 2 O) films consisted of nanosticks and nanoparticles were prepared on fluorine doped tin oxide (FTO)-coated substrate by a facile and template-free hydrothermal method using ammonium acetate (CH 3 COONH 4 ) as the capping agent. Irregular nanobrick films were obtained without capping agent. Due to the highly rough surface, the nanostick/nanoparticle film depicts faster ion intercalation/deintercalation kinetics and a greater coloration efficiency (45.5 cm 2 /C) than the nanobrick film. A complementary electrochromic device based on the nanostick/nanoparticle 3WO 3 ·H 2 O film and Prussian blue (PB) was assembled. As a result, the complementary device shows a higher optical modulation (54% at 754 nm), a larger coloration efficiency (151.9 cm 2 /C) and faster switching responses with a bleaching time of 5.7 s and a coloring time of 1.3 s than a single 3WO 3 ·H 2 O layer device, making it attractive for a practical application.

Immune checkpoint therapy via PD-1 antibodies has shown exciting clinical value and robust therapeutic potential in clinical practice. It can significantly improve progression-free survival and overall survival. Following surgery, radiotherapy, chemotherapy, and targeted therapy, cancer treatment has now entered the age of immunotherapy. Although cancer immunotherapy has shown remarkable efficacy, it also suffers from limitations such as irAEs, cytokine storm, low response rate, etc. In this review, we discuss the basic classification, research progress, and limitations of cancer immunotherapy. Besides, by combining cancer immunotherapy resistance mechanism with analysis of combination therapy, we give our insights into the development of new anticancer immunotherapy strategies.