Tailor-made ß-ketoenamine-linked covalent organic polymer nanofilms for precise molecular sieving.

The membranes that accurately separate solutes with close molecular weights in harsh solvents are of crucial importance for the development of highly-precise organic solvent nanofiltration (OSN). The physicochemical structures of the membrane need to be rationally designed to achieve this goal, such as customized crosslinked networks, thickness, and pore size. Herein, we synthesize a type of covalent organic polymer (COP) nanofilms with tailor-made thickness and pore structure using a cyclic deposition strategy for precise molecular sieving. By elaborately designing monomer structures and controlling deposition cycle numbers, the COP nanofilms linked by robust ß-ketoenamine blocks were endowed with sub-nanometer micropores and a linearly tunable thickness of 10-40 nm. The composite membranes integrating COP nanofilms exhibited adjustable solvent permeance. The membranes further demonstrated steep and finely-regulated rejection curves within the molecular weight range of 200 to 400 Da, where the difference value was as low as 40 Da. The efficient purification and concentration of the antibacterial drug and its intermediate was well achieved. Therefore, the exploited COP nanofilms markedly facilitate the application of microporous organic polymers for precise molecular separation in OSN.

A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.

BACKGROUND: Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a "Tregs-induction"-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. METHODS: The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide in vivo. FINDINGS: Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. INTERPRETATION: SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. FUNDING: This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).

Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut.

BACKGROUND AND AIMS: Although oral berberine, a natural compound extracted from the Chinese herbal medicine curcumin, has low bioavailability, it is still effective in suppressing obesity; however, the underlying mechanism is unclear. Berberine can bind to bitter-taste receptors (TAS2Rs) in intestinal endocrine secretin tumor (STC-1) cells to promote glucagon-like peptide-1 (GLP-1) secretion. Notably, TAS2Rs also exist in the tuft cells of the gut. Therefore, this study aimed to explore whether the beneficial effect of oral berberine on obesity is dependent on bitter-taste signaling in the tuft cells of the gut. METHODS AND RESULTS: Standard chow diet (SCD) or high-fat diet (HFD) was administered to C57BL/6 mice, with or without berberine (100 mg/kg, 200 mg/kg, p. o.). The PLCß2 inhibitor U73122 was used to verify whether the anti-obesity effect of berberine was dependent on the bitter-taste signaling pathway. In this study, we observed that the oral administration of berberine alleviated HFD-induced obesity in mice that U73122 partially inhibited. Both in vivo and ex vivo, berberine upregulated the release of GLP-1, promoted the proliferation of tuft cells and secretion of IL-25 in obesity via the TAS2R signaling pathway. CONCLUSIONS: Oral berberine ameliorated HFD-induced obesity through the TAS2R-IL-25 signaling pathway in tuft cells in the gut. SIGNIFICANCE: We identified and functionally characterized the TAS2Rs and Gα-gustducin/Gß1γ13 signaling pathway utilized by tuft cells in response to oral berberine in obese mice and proposed a new mechanism underlying the anti-obesity effect of berberine.