Core-Corona Magnetic Nanospheres Functionalized with Zwitterionic Polymer Ionic Liquid for Highly Selective Isolation of Glycoprotein.

A novel zwitterionic polymer ionic liquid functionalized magnetic nanospheres, shortly as Fe3O4@PCL-PILs, is synthesized by grafting ionic liquid VimCOOHBr onto polymer ε-caprolactone (PCL) modified magnetic nanospheres via esterification and surface-initiated free radical polymerization. This established synthesis strategy offers the obtained magnetic nanospheres with well-defined core-corona structure, compact grafting layer, favorable zwitterionic and negative-charged surface, and high magnetic susceptibility. The as-prepared Fe3O4@PCL-PILs nanospheres exhibit typical "zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC)" behaviors toward protein binding, and selectively adsorption of glycoprotein is achieved. The adsorption capacity of the magnetic nanospheres toward Immunoglobulin G is high up to 1136.4 mg g-1, and the captured Immunoglobulin G could be efficiently recovered by using 0.5% NH3 H2O (v/v) as stripping reagent, providing a recovery of 80.5%. Fe3O4@PCL-PILs nanospheres are then employed as sorbent for the selective isolation of Immunoglobulin G from human whole blood, obtaining high-purity Immunoglobulin G as demonstrated by polyacrylamide gel electrophoresis assays.

Directional-path modification strategy enhances PET hydrolase catalysis of plastic degradation.

Poly (ethylene terephthalate) (PET) is a widely used type of general plastic that produces a significant amount of waste due to its non-degradable properties. We propose a novel directional-path modification (DPM) strategy, involving positive charge amino acid introduction and binding groove remodeling, and apply it to Thermobifida fusca cutinase to enhance PET degradation. The highest value of PET degradation (90%) was achieved in variant 4Mz (H184S/Q92G/F209I/I213K), exhibiting values almost 30-fold that of the wild-type. We employed molecular docking, molecular dynamics simulations, and QM/MM MD for the degradation process of PET, accompanied by acylation and deacylation. We found that the distance of nucleophilic attack was reduced from about 4.6 Å in the wild type to 3.8 Å in 4Mz, and the free energy barrier of 4Mz dropped from 14.3 kcal/mol to 7.1 kcal/mol at the acylation which was the rate-limiting step. Subsequently, the high efficiency and universality of the DPM strategy were successfully demonstrated in LCC, Est119, and BhrPETase enhancing the degradation activity of PET. Finally, the highest degradation rate of the pretreated commercial plastic bottles had reached to 73%. The present study provides insight into the molecular binding mechanism of PET into the PET hydrolases structure and proposes a novel DPM strategy that will be useful for the engineering of more efficient enzymes for PET degradation.

PEGylated titanate nanosheets: hydrophilic monolayers with a superior capacity for the selective isolation of immunoglobulin G.

A novel organic-inorganic hybrid was prepared by anchoring (3-aminopropyl)triethoxysilane (APTES) on the surface of monolayer titanate nanosheets and subsequent modification with hydrophilic polyethylene glycol (PEG). The PEGylated hydrophilic monolayer titanate nanosheets were abbreviated as PEG-APTES-TiNSs, and they exhibit a lateral dimension of dozens of nanometers and a thickness of ca. 1.9 nm. PEGylation of the titanate nanosheets significantly improved their selectivity toward the adsorption of glycoproteins through strong hydrophilic interaction, providing an adsorption capacity of 2540.9 mg g-1 for immunoglobulin G (IgG). The retained IgG is readily collected at a recovery rate of 83.4% with 0.5% (m/v) ammonium hydroxide (NH4OH) as the stripping reagent. PEG-APTES-TiNSs are applied for the selective adsorption of IgG from human serum, which is further confirmed by SDS-PAGE assay.

Sirolimus conversion in liver transplant recipients with calcineurin inhibitor-induced complications: efficacy and safety.

OBJECTIVES: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. MATERIALS AND METHODS: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. RESULTS: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. CONCLUSIONS: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.