Profiling the differential phosphoproteome between breast milk and infant formula through a titanium (IV)-immobilized magnetic nanoplatform.

Breast milk (BM) fulfills the nutritional needs of infants and sets the standard for infant formula (IF). However, profiling the differential phosphoproteome between BM and IF remains unclear. Herein, a titanium (IV) (Ti4+)-immobilized magnetic nanoplatform (Fe3O4@GO@PDA-Ti4+) was constructed by self-assembly polymerization of dopamine on magnetic graphene oxide, followed by immobilizing Ti4+ through chelation for phosphopeptide enrichment. Fe3O4@GO@PDA-Ti4+ possessed outstanding selectivity (1/1000, a molar ratio of ß-casein digests to bovine serum albumin digests) and favorable sensitivity (2.5 fmol/µL), along with rapid magnetic separation. Excellent phosphopeptide capture efficiencies were obtained for BM and IF using Fe3O4@GO@PDA-Ti4+ as an adsorbent coupled with liquid chromatography-mass spectrometry/mass spectrometry. There were 191 and 239 phosphopeptides found in BM and IF, respectively, with 36 phosphoproteins identified in both. However, BM and IF shared only 17 phosphopeptides and 4 phosphoproteins. The variation in the phosphoproteome between BM and IF provides valuable insights into the optimization of IF humanization.

A Biomimetic Nanoplatform with Improved Inflammatory Targeting Behavior for ROS Scavenging-Based Treatment of Ulcerative Colitis.

Ulcerative colitis (UC), a refractory disease, has become a global problem. Herein, a biomimetic nanoplatform (AU-LIP-CM) comprising Au cluster enzymes (AU)-loaded liposomes (AU-LIP) camouflaged with the fusion membrane (CM) consisting of neutrophil (NC) and red blood cell (RBC) membrane is designed for the treatment of UC. Briefly, revealed by second near-infrared (NIR-II) imaging through collection of fluorescence emitting >1200 nm from AU, the improved inflammatory targeting behavior contributed by CM cloaking, which inherits abilities of inflammatory targeting and immune escape from NC and RBC, respectively, promotes specific accumulation of AU within inflammatory intestines with up to ≈11.5 times higher than that of bare AU. Afterward, AU possessing superoxide dismutase- and catalase-like activities realizes high-efficiency scavenging of reactive oxygen species (ROS), leading to repair of intestinal barriers, regulation of the immune system, and modulation of gut microbiota, which surpass first-line UC drug. In addition, study of underlying therapeutic mechanism demonstrated that the treatment with AU-LIP-CM can alter the gene signature associated with response to ROS for UC mice to a profile similar to that of healthy mice, deciphering related signal pathways. The strategy developed here provides insights of learning from properties of natural bio-substances to empower biomimetic nanoplatform to confront diseases.

Modified Prebiotic-Based "Shield" Armed Probiotics with Enhanced Resistance of Gastrointestinal Stresses and Prolonged Intestinal Retention for Synergistic Alleviation of Colitis.

Oral administration of probiotics is a promising method to alleviate inflammatory bowel diseases (IBDs). However, gastrointestinal environmental sensitivity and inferior intestinal colonization of probiotics hinder the alleviation effect. Here, we developed a simple yet effective modified prebiotic-based "shield" (Fe-TA@mGN) composed of an Fe3+-tannic acid cross-linking network and carboxymethylated ß-glucan for arming Escherichia coli Nissle 1917 (EcN@Fe-TA@mGN). The Fe-TA@mGN "shield" not only acted as a dynamic barrier to enhance the gastrointestinal stress resistance ability of EcN but also aided the intestinal colonization of EcN as well as synergized with EcN for the alleviation of dextran sulfate sodium (DSS) induced colitis. More specifically, with the protection of the Fe-TA@mGN "shield", the survival rate of armed EcN could be up to ∼1720 times higher than that of bare EcN after exposure to simulated gastric fluid. Excitingly, the intestinal retention rate of EcN@Fe-TA@mGN was as high as 47.54 ± 6.06% at 16 h post-administration, while almost all bare EcNs were excreted out at 8 h post-administration. With all of the aforementioned attributes, EcN@Fe-TA@mGN efficiently alleviated colitis, verified by the repair of the intestinal barrier and the attenuation of inflammation. Moreover, for EcN@Fe-TA@mGN, mGN synergized with EcN to positively modulate gut microbiota and promote the production of short-chain fatty acids (SCFAs, especially for butyric acid, a primary source for maintaining intestinal health), both of which would further advance the alleviation of colitis. We envision that the strategy developed here will inspire the exploitation of various prebiotics to arm probiotics for the effective alleviation of IBD.

Thermosensitive and magnetic molecularly imprinted polymers for selective recognition and extraction of aristolochic acid I.

Recently, the natural compound of aristolochic acid I (AAI) has attracted wide attentions due to its strong nephrotoxicity and carcinogenicity. However, the extraction of AAI based on conventional molecularly imprinted polymers (MIPs) are tedious with extensive eluent, causing secondary pollution and poor regeneration. Herein, thermosensitive and magnetic MIPs (TMMIPs) were synthesized by a surface imprinting method, which achieved thermosensitive capture/release of AAI, along with rapid magnetic separation, significantly shortening the elution time and reducing organic-solvent consumption. TMMIPs with dual-stimuli responses exhibited superior affinity, selectivity, kinetics, and regeneration ability towards AAI. TMMIPs were applied to analyze AAI in Houttuynia cordata via dispersive solid-phase extraction (d-SPE) coupled with high performance liquid chromatography (HPLC), yielding satisfactory recoveries (79.03-99.67%) and relative standard deviations (≤5.78%). The limit of detection of AAI was as low as 26.67 µg/L. TMMIPs demonstrate great applicability for fast, selective and eco-friendly extraction of AAI in complicated matrices.

A magnetic hydrophilic molecularly imprinted material with multiple stimuli-response properties for efficient recognition of bisphenol A in beverages.

A magnetic hydrophilic molecularly imprinted material (MIM) with multiple stimuli-responses was prepared for efficient recognition of bisphenol A (BPA). MIM consisted of a magnetic core, an inner silica dioxide shell and an outer hydrophilic polymer shell, responsive for rapid magnetic separation, protection of the magnetic core and pH-/thermo-sensitivity to BPA, respectively. Controlled adsorption and release of BPA by pH/temperature regulation were realized through the reversible components of poly[N-isopropylacrylamide-co-2-(dimethylamino)ethyl methacrylate (NIPAM-DMAEMA)] (PND). The resultant MIM possessed superior affinity, selectivity and kinetics to BPA in aqueous solution. MIM was successfully applied to detect BPA in beverages via dispersive solid-phase extraction (d-SPE) coupled with high performance liquid chromatography (HPLC), exhibiting satisfactory recoveries of 80.70-108.18% with relative standard deviations (RSD) below 6.08%. The limit of detection of BPA was obtained as low as 3.75 nmol/L. The versatile MIM could be a promising alternative for extraction/removal of BPA in complicated samples by multiple-stimuli regulations.

Switchable zipper-like thermoresponsive molecularly imprinted polymers for selective recognition and extraction of estradiol.

Zipper-like thermoresponsive molecularly imprinted polymers (MIPs) were prepared based on interpolymer complexation via the synergy of dual functional monomers of acrylamide (AAm) and 2-acrylamide-2-methyl propanesulfonic acid (AMPS) for selective recognition and extraction of estradiol (E2) by temperature regulation. The resulting E2-MIPs attained controlled adsorption and release of E2 in response to temperature change, with higher adsorption capacity (8.78mg/g) and stronger selectivity (imprinting factor was 3.18) at 30°C compared with that at 20 and 40°C; the zipper-like interpolymer interaction between poly(AAm) and poly(AMPS) enabled switchable molecular recognition. The adsorption processes obeyed Langmuir isotherm and pseudo-second-order kinetic models. High recognition selectivity of the MIPs toward E2 was achieved over its structural analogues, and good reusability was displayed over 86% recovery after six adsorption-desorption cycles. Accordingly, the E2-MIPs were empolyed as new adsorbents for selective dispersive solid-phase extraction of E2, and offered low limits of detection and quantification of 4.81 and 16.03µg/L, respectively. Recoveries from goat milk samples ranged from 76.2% to 89.7% with the precisions (relative standard deviations, n = 3, %) of 2.8-3.7% at 30°C. The intelligent E2-MIPs combining good adsorption, special recognition and temperature sensitivity proved to be a promising alternative to the selective identification and controlled extraction/removal of E2 in complicated samples by simple temperature-responsive regulation.